title: Cult

text: "Destructive cult" generally refers to groups whose members have, through deliberate action, physically injured or killed other members of their own group or other people. The Ontario Consultants on Religious Tolerance specifically limits the use of the term to religious groups that "have caused or are liable to cause loss of life among their membership or the general public." Psychologist Michael Langone, executive director of the anti-cult group International Cultic Studies Association, defines a destructive cult as "a highly manipulative group which exploits and sometimes physically and/or psychologically damages members and recruits."


title: Cult

text: John Gordon Clark argued that totalitarian systems of governance and an emphasis on money making are characteristics of a destructive cult. In "Cults and the Family", the authors cite Shapiro, who defines a "destructive cultism" as a sociopathic syndrome, whose distinctive qualities include: "behavioral and personality changes, loss of personal identity, cessation of scholastic activities, estrangement from family, disinterest in society and pronounced mental control and enslavement by cult leaders."


title: Cult

text: In the opinion of Sociology Professor Benjamin Zablocki of Rutgers University, "destructive cults" are at high risk of becoming abusive to members, stating that such is in part due to members' adulation of charismatic leaders contributing to the leaders becoming corrupted by power. According to Barrett, the most common accusation made against destructive cults is sexual abuse. According to Kranenborg, some groups are risky when they advise their members not to use regular medical care. This may extend to physical and psychological harm.


title: Cult

text: Writing about Bruderhof communities in the book "Misunderstanding Cults: Searching for Objectivity in a Controversial Field", Julius H. Rubin said that American religious innovation created an unending diversity of sects. These "new religious movements…gathered new converts and issued challenges to the wider society. Not infrequently, public controversy, contested narratives and litigation result." In his work "Cults in Context" author Lorne L. Dawson writes that although the Unification Church "has not been shown to be violent or volatile," it has been described as a destructive cult by "anticult crusaders." In 2002, the German government was held by the Federal Constitutional Court to have defamed the Osho movement by referring to it, among other things, as a "destructive cult" with no factual basis.


title: Cult

text: Some researchers have criticized the usage of the term "destructive cult", writing that it is used to describe groups which are not necessarily harmful in nature to themselves or others. In his book "Understanding New Religious Movements", John A. Saliba writes that the term is overgeneralized. Saliba sees the Peoples Temple as the "paradigm of a destructive cult", where those that use the term are implying that other groups will also commit mass suicide.


title: Cult

text: "Doomsday cult" is an expression which is used to describe groups that believe in Apocalypticism and Millenarianism, and it can also be used to refer both to groups that predict disaster, and groups that attempt to bring it about. In the 1950s, American social psychologist Leon Festinger and his colleagues observed members of a small UFO religion called the Seekers for several months, and recorded their conversations both prior to and after a failed prophecy from their charismatic leader. Their work was later published in the book "When Prophecy Fails: A Social and Psychological Study of a Modern Group that Predicted the Destruction of the World". In the late 1980s, doomsday cults were a major topic of news reports, with some reporters and commentators considering them a serious threat to society. A 1997 psychological study by Festinger, Riecken, and Schachter found that people turned to a cataclysmic world view after they had repeatedly failed to find meaning in mainstream movements. People also strive to find meaning in global events such as the turn of the millennium when many predicted it prophetically marked the end of an age and thus the end of the world. An ancient Mayan calendar ended at the year 2012 and many anticipated catastrophic disasters would rock the Earth.


title: Cult

text: A political cult is a cult with a primary interest in political action and ideology. Groups that some have described as "political cults", mostly advocating far-left or far-right agendas, have received some attention from journalists and scholars. In their 2000 book "", Dennis Tourish and Tim Wohlforth discuss about a dozen organizations in the United States and Great Britain that they characterize as cults. In a separate article, Tourish says that in his usage: The word cult is not a term of abuse, as this paper tries to explain. It is nothing more than a shorthand expression for a particular set of practices that have been observed in a variety of dysfunctional organisations.


title: Cult

text: In 1990, Lucy Patrick commented:Although we live in a democracy, cult behavior manifests itself in our unwillingness to question the judgment of our leaders, our tendency to devalue outsiders and to avoid dissent. We can overcome cult behavior, he says, by recognizing that we have dependency needs that are inappropriate for mature people, by increasing anti-authoritarian education, and by encouraging personal autonomy and the free exchange of ideas.


title: Cult

text: In Iran, a "cult of Khomeini" developed into a "secular religion". According to Iranian author Amir Taheri, Khomeini is called imam, making a "Twelver Shiism into a cult of Thirteen." Khomeini’s image is engraved in giant rocks and mountain slopes, prayers begin and end with his name, and his fatwas remain valid beyond his death (something that goes against Shiite principles). Also slogans such as "God, Koran, Khomeini" or "God is One, Khomeini is the Leader" are used as war cries of the Hezballah in Iran. Even though Khomeini’s photographs still hang in many government offices, it is said that by the late 1990s “Khomeini’s cult had faded”.


title: Cult

text: Followers of Ayn Rand have been characterized as a cult by economist Murray N. Rothbard during her lifetime, and later by Michael Shermer. The core group around Rand was called the "Collective", which are now defunct; the chief group which is disseminating Rand's ideas today is the Ayn Rand Institute. Although the Collective advocated an individualist philosophy, Rothbard claimed that it was organized in the manner of a "Leninist" organization.


title: Cult

text: The LaRouche movement is a political and cultural network promoting the late Lyndon LaRouche and his ideas. It has included many organizations and companies around the world, which campaign, gather information and publish books and periodicals. It has been called "cult-like" by "The New York Times".


title: Cult

text: The movement originated within the radical leftist student politics of the 1960s. In the 1970s and 1980s hundreds of candidates ran in state Democratic primaries in the United States on the 'LaRouche platform', while Lyndon LaRouche repeatedly campaigned for presidential nomination. However, the LaRouche movement is often considered far-right. During its peak in the 1970s and 1980s, the LaRouche movement developed a private intelligence agency and contacts with foreign governments.


title: Cult

text: An Argentinian esoteric group founded in 1957 by former theosophist Jorge Angel Livraga, the New Acropolis Cultural Association has been described by scholars as an ultra-conservative, neo-fascist and white supremacist paramilitary group. The group itself denies such descriptions.


title: Cult

text: Founded by North Korea-born Sun Myung Moon, the Unification Church (also known as the Unification movement) holds a strong anti-Communist position. In the 1940s, Moon cooperated with members of the Communist Party of Korea in the Korean independence movement against Imperial Japan. However, after the Korean War (1950–1953), he became an outspoken anti-communist. Moon viewed the Cold War between democracy and communism as the final conflict between God and Satan, with divided Korea as its primary front line. Soon after its founding the Unification movement began supporting anti-communist organizations, including the World League for Freedom and Democracy founded in 1966 in Taipei, Republic of China (Taiwan), by Chiang Kai-shek, and the Korean Culture and Freedom Foundation, an international public diplomacy organization which also sponsored Radio Free Asia.


title: Cult

text: In 1974 the Unification Church supported Republican President Richard Nixon and rallied in his favor after the Watergate scandal, with Nixon thanking personally for it. In 1975 Moon spoke at a government sponsored rally against potential North Korean military aggression on Yeouido Island in Seoul to an audience of around 1 million. The Unification movement was criticized by both the mainstream media and the alternative press for its anti-communist activism, which many said could lead to World War Three and a nuclear holocaust.


title: Cult

text: In 1977, the Subcommittee on International Organizations of the Committee on International Relations, of the United States House of Representatives, found that the South Korean intelligence agency, the KCIA, had used the movement to gain political influence with the United States and that some members had worked as volunteers in Congressional offices. Together they founded the Korean Cultural Freedom Foundation, a nonprofit organization which acted as a public diplomacy campaign for the Republic of Korea. The committee also investigated possible KCIA influence on the Unification Church's campaign in support of Nixon.


title: Cult

text: In 1980, members founded CAUSA International, an anti-communist educational organization based in New York City. In the 1980s, it was active in 21 countries. In the United States, it sponsored educational conferences for evangelical and fundamentalist Christian leaders as well as seminars and conferences for Senate staffers, Hispanic Americans and conservative activists. In 1986, CAUSA International sponsored the documentary film "Nicaragua Was Our Home", about the Miskito Indians of Nicaragua and their persecution at the hands of the Nicaraguan government. It was filmed and produced by USA-UWC member Lee Shapiro, who later died while filming with anti-Soviet forces during the Soviet–Afghan War.


title: Cult

text: In 1983, some American members joined a public protest against the Soviet Union over its shooting down of Korean Airlines Flight 007. In 1984, the HSA–UWC founded the Washington Institute for Values in Public Policy, a Washington D.C. think tank that underwrites conservative-oriented research and seminars at Stanford University, the University of Chicago, and other institutions. In the same year, member Dan Fefferman founded the International Coalition for Religious Freedom in Virginia, which is active in protesting what it considers to be threats to religious freedom by governmental agencies. In August 1985 the Professors World Peace Academy, an organization founded by Moon, sponsored a conference in Geneva to debate the theme "The situation in the world after the fall of the communist empire."


title: Cult

text: In April 1990, Moon visited the Soviet Union and met with President Mikhail Gorbachev. Moon expressed support for the political and economic transformations underway in the Soviet Union. At the same time, the movement was expanding into formerly communist nations. In 1994, "The New York Times" recognized the movement's political influence, saying it was "a theocratic powerhouse that is pouring foreign fortunes into conservative causes in the United States." In 1998, the Egyptian newspaper "Al-Ahram" criticized Moon's "ultra-right leanings" and suggested a personal relationship with conservative Israeli prime minister Benjamin Netanyahu.


title: Cult

text: The Unification Church also owns several news outlets including "The Washington Times", "Insight on the News", United Press International and the News World Communications network. "Washington Times" opinion editor Charles Hurt was one of Donald Trump's earliest supporters in Washington, D.C. In 2018, he included Trump with Ronald Reagan, Martin Luther King Jr., Margaret Thatcher, and Pope John Paul II as "great champions of freedom." In 2016 "The Washington Times" did not endorse a candidate for United States president, but endorsed Trump for reelection in 2020.


title: Cult

text: In Britain, the Workers Revolutionary Party (WRP), a Trotskyist group which was led by Gerry Healy and strongly supported by actress Vanessa Redgrave, has been described by others, who have been involved in the Trotskyist movement, as having been a cult or a group which displayed cult-like characteristics during the 1970s and 1980s. It is also described as such by Wohlforth and Tourish, to whom Bob Pitt, a former member of the WRP, concedes that it had a "cult-like character" though arguing that rather than being typical of the far left, this feature actually made the WRP atypical and "led to its being treated as a pariah within the revolutionary left itself."


title: Cult

text: Organizations like the Mexican far-right group El Yunque, which sponsored the Spanish far right party Vox, the QAnon conspiracy theory, and the growing neo-Pentecostal political influence in Latin America, can be characterised as cults.


title: Cult

text: Gino Perente's National Labor Federation (NATLFED) and Marlene Dixon's now-defunct Democratic Workers Party are an examples of political groups that have been described as "cults". A critical history of the DWP is given in "Bounded Choice" by Janja Lalich, a sociologist and former DWP member. Lutte Ouvrière (LO; "Workers' Struggle") in France, publicly headed by Arlette Laguiller but revealed in the 1990s to be directed by Robert Barcia, has often been criticized as a cult, for example, by Daniel Cohn-Bendit and his older brother Gabriel Cohn-Bendit, as well as by "L'Humanité" and "Libération".


title: Cult

text: In his book "Les Sectes Politiques: 1965–1995" ("Political cults: 1965–1995"), French writer Cyril Le Tallec considers some religious groups that were involved in politics at that time. He included the Cultural Office of Cluny, New Acropolis, the Divine Light Mission, Tradition Family Property (TFP), Longo Maï, the Supermen Club, and the Association for Promotion of the Industrial Arts (Solazaref).


title: Cult

text: Several former leaders of the Groyper movement — an alt-right faction that infuses white supremacy, Christian nationalism, and Incel ideology — have accused Nick Fuentes of leading it like a cult, describing him as abusing and demanding absolute loyalty from his followers. Fuentes praised having a "cult-like... mentality" and admitted to "ironically" describing his own movement as a cult.


title: Cult

text: Cults that teach and practice polygamy, marriage between more than two people, most often polygyny, one man having multiple wives, have long been noted, although they are a minority. It has been estimated that there are around 50,000 members of polygamist cults in North America. Often, polygamist cults are viewed negatively by both legal authorities and mainstream society, and this view sometimes includes negative perceptions of related mainstream denominations, because of their perceived links to possible domestic violence and child abuse.


title: Cult

text: From the 1830s, members of the Church of Jesus Christ of Latter-day Saints (LDS Church) practiced polygamy, or plural marriage. In 1890, the president of the LDS Church, Wilford Woodruff, issued a public manifesto which announced that the LDS Church had ceased performing new plural marriages. Anti-Mormon sentiment waned, as did opposition to statehood for Utah. The Smoot Hearings in 1904, which documented that members of the LDS Church were still practising polygamy, spurred the church to issue a Second Manifesto, again claiming that it had ceased performing new plural marriages. By 1910, the LDS Church excommunicated those who entered into or performed new plural marriages. Enforcement of the 1890 Manifesto caused various splinter groups to leave the LDS Church in order to continue the practice of plural marriage. Such groups are known as Mormon fundamentalists. For example, the Fundamentalist Church of Jesus Christ of Latter-Day Saints is often described as a polygamist cult.


title: Cult

text: Sociologist and historian Orlando Patterson has described the Ku Klux Klan, which arose in the American South after the Civil War, as a heretical Christian cult, and he has also described its persecution of African Americans and others as a form of human sacrifice. During the nineteenth and early twentieth centuries, the existence of secret Aryan cults in Germany and Austria strongly influenced the rise of Nazism. Modern-day white power skinhead groups in the United States tend to use the same recruitment techniques as groups which are characterized as destructive cults.


title: Cult

text: Vibert L. White, Jr., a former member and lead advisor for Nation of Islam, characterized the organization as a cult, accusing its leader Louis Farrakhan, along with other organizational leaders, of using black nationalism and religious dogma to exploit black people for personal and political gain. The Nation of Islam preaches black supremacy, that its founder Wallace Fard Muhammad was a Messiah and his successor Elijah Muhammad was a divine messenger, and that white people were a race of devils to be overthrown apocalyptically.


title: Cult

text: In the book "Jihad and Sacred Vengeance: Psychological Undercurrents of History", psychiatrist Peter A. Olsson compares Osama bin Laden to certain cult leaders including Jim Jones, David Koresh, Shoko Asahara, Marshall Applewhite, Luc Jouret and Joseph Di Mambro, and he also says that each of these individuals fit at least eight of the nine criteria for people with narcissistic personality disorders. In the book "Seeking the Compassionate Life: The Moral Crisis for Psychotherapy and Society" authors Goldberg and Crespo also refer to Osama bin Laden as a "destructive cult leader."


title: Cult

text: At a 2002 meeting of the American Psychological Association (APA), anti-cultist Steven Hassan said that Al-Qaeda fulfills the characteristics of a destructive cult, adding, in addition:


title: Cult

text: We need to apply what we know about destructive mind-control cults, and this should be a priority in the War on Terrorism. We need to understand the psychological aspects of how people are recruited and indoctrinated so we can slow down recruitment. We need to help counsel former cult members and possibly use some of them in the war against terrorism.


title: Cult

text: In an article on Al-Qaeda published in "The Times", journalist Mary Ann Sieghart wrote that al-Qaeda resembles a "classic cult:"


title: Cult

text: Al-Qaeda fits all the official definitions of a cult. It indoctrinates its members; it forms a closed, totalitarian society; it has a self-appointed, messianic and charismatic leader; and it believes that the ends justify the means.


title: Cult

text: Similar to Al-Qaeda, the Islamic State of Iraq and the Levant adheres to an even more extremist and puritanical ideology, in which the goal is to create a state governed by "shari'ah" as interpreted by its religious leadership, who then brainwash and command their able-bodied male subjects to go on suicide missions, with such devices as car bombs, against its enemies, including deliberately-selected civilian targets, such as churches and Shi'ite mosques, among others. Subjects view this as a legitimate action; an obligation, even. The ultimate goal of this political-military endeavour is to eventually usher in the end of the world in accordance with their Islamic beliefs and have the chance to participate in their version of the apocalyptic final battle, in which all of their enemies (i.e. anyone who is not on their side) would be annihilated. Such endeavour ultimately failed in 2017, though hardcore survivors have largely returned to insurgency terrorism (i.e., Iraqi insurgency, 2017–present).


title: Cult

text: The Shining Path guerrilla movement, active in Peru in the 1980s and 1990s, has variously been described as a "cult" and an intense "cult of personality". The Tamil Tigers have also been described as such by the French magazine "L'Express".


title: Cult

text: In the 1940s, the long-held opposition by some established Christian denominations to non-Christian religions and supposedly heretical or counterfeit Christian sects crystallized into a more organized Christian countercult movement in the United States. For those belonging to the movement, all religious groups claiming to be Christian, but deemed outside of Christian orthodoxy, were considered cults. Christian cults are new religious movements that have a Christian background but are considered to be theologically deviant by members of other Christian churches. In his influential book "The Kingdom of the Cults" (1965), Christian scholar Walter Ralston Martin defines Christian cults as groups that follow the personal interpretation of an individual, rather than the understanding of the Bible accepted by Nicene Christianity, providing the examples of the Church of Jesus Christ of Latter-day Saints, Christian Science, Jehovah's Witnesses, and the Unity Church.


title: Cult

text: The Christian countercult movement asserts that Christian sects whose beliefs are partially or wholly not in accordance with the Bible are erroneous. It also states that a religious sect can be considered a cult if its beliefs involve a denial of what they view as any of the essential Christian teachings such as salvation, the Trinity, Jesus himself as a person, the ministry of Jesus, the miracles of Jesus, the crucifixion, the resurrection of Christ, the Second Coming, and the rapture.


title: Cult

text: Countercult literature usually expresses doctrinal or theological concerns and a missionary or apologetic purpose. It presents a rebuttal by emphasizing the teachings of the Bible against the beliefs of non-fundamental Christian sects. Christian countercult activist writers also emphasize the need for Christians to evangelize to followers of cults.


title: Cult

text: In the early 1970s, a secular opposition movement to groups considered cults had taken shape. The organizations that formed the secular anti-cult movement (ACM) often acted on behalf of relatives of "cult" converts who did not believe their loved ones could have altered their lives so drastically by their own free will. A few psychologists and sociologists working in this field suggested that brainwashing techniques were used to maintain the loyalty of cult members. The belief that cults brainwashed their members became a unifying theme among cult critics and in the more extreme corners of the anti-cult movement techniques like the sometimes forceful "deprogramming" of cult members was practised.


title: Cult

text: Secular cult opponents belonging to the anti-cult movement usually define a "cult" as a group that tends to manipulate, exploit, and control its members. Specific factors in cult behaviour are said to include manipulative and authoritarian mind control over members, communal and totalistic organization, aggressive proselytizing, systematic programs of indoctrination, and perpetuation in middle-class communities. In the mass media, and among average citizens, "cult" gained an increasingly negative connotation, becoming associated with things like kidnapping, brainwashing, psychological abuse, sexual abuse and other criminal activity, and mass suicide. While most of these negative qualities usually have real documented precedents in the activities of a very small minority of new religious groups, mass culture often extends them to any religious group viewed as culturally deviant, however peaceful or law abiding it may be.


title: Cult

text: While some psychologists were receptive to these theories, sociologists were for the most part sceptical of their ability to explain conversion to NRMs. In the late 1980s, psychologists and sociologists started to abandon theories like brainwashing and mind control. While scholars may believe that various less dramatic coercive psychological mechanisms could influence group members, they came to see conversion to new religious movements principally as an act of a rational choice.


title: Cult

text: Because of the increasingly pejorative use of the words "cult" and "cult leader" since the cult debate of the 1970s, some academics, in addition to groups referred to as cults, argue that these are words to be avoided. Catherine Wessinger (Loyola University New Orleans) has stated that the word "cult" represents just as much prejudice and antagonism as racial slurs or derogatory words for women and homosexuals. She has argued that it is important for people to become aware of the bigotry conveyed by the word, drawing attention to the way it dehumanizes the group's members and their children. Labelling a group as subhuman, she says, becomes a justification for violence against it. She also says that labelling a group a "cult" makes people feel safe, because the "violence associated with religion is split off from conventional religions, projected onto others, and imagined to involve only aberrant groups." According to her, this fails to take into account that child abuse, sexual abuse, financial extortion and warfare have also been committed by believers of mainstream religions, but the pejorative "cult" stereotype makes it easier to avoid confronting this uncomfortable fact.


title: Cult

text: The application of the labels "cult" or "sect" to religious movements in government documents signifies the popular and negative use of the term "cult" in English and a functionally similar use of words translated as "sect" in several European languages. Sociologists critical to this negative politicized use of the word "cult" argue that it may adversely impact the religious freedoms of group members. At the height of the counter-cult movement and ritual abuse scare of the 1990s, some governments published lists of cults. While these documents utilize similar terminology they do not necessarily include the same groups nor is their assessment of these groups based on agreed criteria. Other governments and world bodies also report on new religious movements but do not use these terms to describe the groups. Since the 2000s, some governments have again distanced themselves from such classifications of religious movements. While the official response to new religious groups has been mixed across the globe, some governments aligned more with the critics of these groups to the extent of distinguishing between "legitimate" religion and "dangerous", "unwanted" cults in public policy.


title: Cult

text: For centuries, governments in China have categorized certain religions as "xiéjiào" (), sometimes translated as "evil cults" or "heterodox teachings". In imperial China, the classification of a religion as "xiejiao" did not necessarily mean that a religion's teachings were believed to be false or inauthentic, rather, the label was applied to religious groups that were not authorized by the state, or it was applied to religious groups that were believed to challenge the legitimacy of the state. In modern China, the term "xiejiao" continues to be used to denote teachings that the government disapproves of, and these groups face suppression and punishment by authorities. Fourteen different groups in China have been listed by the ministry of public security as "xiejiao". Additionally, in 1999, Chinese Communist Party authorities denounced the Falun Gong spiritual practice as a heretical teaching, and they launched a campaign to eliminate it. However, such claims only exist in party resolutions, and has not been legitimized by Chinese own law systems. This actually made such denouncement confusing and as outlawed actions secretly conducted by Communist Party's secret policemen. According to Amnesty International, the persecution of Falun Gong includes a multifaceted propaganda campaign, a program of enforced ideological conversion and re-education, as well as a variety of extralegal coercive measures, such as arbitrary arrests, forced labour, and physical torture, sometimes resulting in death.


title: Cult

text: In 2008 the Russian Interior Ministry prepared a list of "extremist groups". At the top of the list were Islamic groups outside of "traditional Islam", which is supervised by the Russian government. Next listed were "Pagan cults". In 2009 the Russian Ministry of Justice created a council which it named the "Council of Experts Conducting State Religious Studies Expert Analysis." The new council listed 80 large sects which it considered potentially dangerous to Russian society, and it also mentioned that there were thousands of smaller ones. The large sects which were listed included: The Church of Jesus Christ of Latter-day Saints, the Jehovah's Witnesses, and other sects which were loosely referred to as "neo-Pentecostals".


title: Cult

text: In the 1970s, the scientific status of the "brainwashing theory" became a central topic in U.S. court cases where the theory was used to try to justify the use of the forceful deprogramming of cult members. Meanwhile, sociologists who were critical of these theories assisted advocates of religious freedom in defending the legitimacy of new religious movements in court. In the United States the religious activities of cults are protected under the First Amendment of the United States Constitution, which prohibits governmental establishment of religion and protects freedom of religion, freedom of speech, freedom of the press, and freedom of assembly. However, no members of religious groups or cults are granted any special immunity from criminal prosecution. In 1990, the court case of "United States v. Fishman" (1990) ended the usage of brainwashing theories by expert witnesses such as Margaret Singer and Richard Ofshe. In the case's ruling, the court cited the Frye standard, which states that the scientific theory which is utilized by expert witnesses must be generally accepted in their respective fields. The court deemed brainwashing to be inadmissible in expert testimonies, using supporting documents which were published by the APA Task Force on Deceptive and Indirect Methods of Persuasion and Control, literature from previous court cases in which brainwashing theories were used, and expert testimonies which were delivered by scholars such as Dick Anthony.


title: Cult

text: The governments of France and Belgium have taken policy positions which accept "brainwashing" theories uncritically, while the governments of other European nations, such as those of Sweden and Italy, are cautious with regard to brainwashing and as a result, they have responded more neutrally with regard to new religions. Scholars have suggested that the outrage which followed the mass murder/suicides which were perpetuated by the Solar Temple have significantly contributed to European anti-cult positions as well as more latent xenophobic and anti-American attitudes which are widespread on the continent. In the 1980s clergymen and officials of the French government expressed concern that some orders and other groups within the Roman Catholic Church would be adversely affected by anti-cult laws which were then being considered.


title: Nonprofit organization

text: A nonprofit organization (NPO) or non-profit organisation, also known as a non-business entity, not-for-profit organization, or nonprofit institution, is a legal entity organized and operated for a collective, public or social benefit, in contrast with an entity that operates as a business aiming to generate a profit for its owners. A nonprofit is subject to the non-distribution constraint: any revenues that exceed expenses must be committed to the organization's purpose, not taken by private parties. An array of organizations are nonprofit, including some political organizations, schools, business associations, churches, social clubs, and consumer cooperatives. Nonprofit entities may seek approval from governments to be tax-exempt, and some may also qualify to receive tax-deductible contributions, but an entity may incorporate as a nonprofit entity without securing tax-exempt status.


title: Nonprofit organization

text: Key aspects of nonprofits are accountability, trustworthiness, honesty, and openness to every person who has invested time, money, and faith into the organization. Nonprofit organizations are accountable to the donors, founders, volunteers, program recipients, and the public community. Theoretically, for a nonprofit that seeks to finance its operations through donations, public confidence is a factor in the amount of money that a nonprofit organization is able to raise. Supposedly, the more nonprofits focus on their mission, the more public confidence they will have. This will result in more money for the organization. The activities a nonprofit is partaking in can help build the public's confidence in nonprofits, as well as how ethical the standards and practices are.


title: Nonprofit organization

text: According to the National Center for Charitable Statistics (NCCS), there are more than 1.5 million nonprofit organizations registered in the United States, including public charities, private foundations, and other nonprofit organizations. Private charitable contributions increased for the fourth consecutive year in 2017 (since 2014), at an estimated $410.02 billion. Out of these contributions, religious organizations received 30.9%, education organizations received 14.3%, and human services organizations received 12.1%. Between September 2010 and September 2014, approximately 25.3% of Americans over the age of 16 volunteered for a nonprofit.


title: Nonprofit organization

text: In the United States, both nonprofits are tax-exempt. There are various types of nonprofit exemptions, such as 501(c)(3) organizations that are a religious, charitable, or educational-based organization that does not influence state and federal legislation, and 501(c)(7) organizations that are for pleasure, recreation, or another nonprofit purpose.


title: Nonprofit organization

text: Nonprofits may be member-serving or community-serving. Member-serving nonprofit organizations create a benefit for the members of their organization and can include but are not limited to credit unions, sports clubs, and advocacy groups. Community-serving nonprofit organizations focus on providing services to the community either globally or locally. Community-serving nonprofits include organizations that deliver aid and development programs, medical research, education, and health services. It is possible for a nonprofit to be both member-serving and community-serving.


title: Nonprofit organization

text: Nonprofit organisations are not driven by generating profit, but they must bring in enough income to pursue their social goals. Nonprofits are able to raise money in different ways. This includes income from donations from individual donors or foundations; sponsorship from corporations; government funding; programs, services or merchandise sales, and investments. Each NPO is unique in which source of income works best for them. With an increase in NPO's within the last decade, organizations have adopted competitive advantages to create revenue for themselves to remain financially stable. Donations from private individuals or organizations can change each year and government grants have diminished. With changes in funding from year to year, many nonprofit organizations have been moving toward increasing the diversity of their funding sources. For example, many nonprofits that have relied on government grants have started fundraising efforts to appeal to individual donors.


title: Nonprofit organization

text: A common misconception about nonprofits is that they are run completely by volunteers. Most nonprofits have staff that work for the company, possibly using volunteers to perform the nonprofit's services under the direction of the paid staff. Nonprofits must be careful to balance the salaries paid to staff against the money paid to provide services to the nonprofit's beneficiaries. Organizations whose salary expenses are too high relative to their program expenses may face regulatory scrutiny.


title: Nonprofit organization

text: A second misconception is that nonprofit organizations may not make a profit. Although the goal of nonprofits is not specifically to maximize profits, they still have to operate as a fiscally responsible business. They must manage their income (both grants and donations and income from services) and expenses so as to remain a fiscally viable entity. Nonprofits have the responsibility of focusing on being professional, financially responsible, replacing self-interest and profit motive with mission motive.


title: Nonprofit organization

text: Though nonprofits are managed differently from for-profit businesses, they have felt pressure to be more businesslike. To combat private and public business growth in the public service industry, nonprofits have modeled their business management and mission, shifting their raison d’être to establish sustainability and growth.


title: Nonprofit organization

text: Setting effective missions is a key for the successful management of nonprofit organizations. There are three important conditions for effective mission: opportunity, competence, and commitment.


title: Nonprofit organization

text: One way of managing the sustainability of nonprofit organizations is to establish strong relations with donor groups. This requires a donor marketing strategy, something many nonprofits lack.


title: Nonprofit organization

text: Nonprofit organizations provide public goods that are undersupplied by government. NPOs have a wide diversity of structures and purposes. For legal classification, there are, nevertheless, some elements of importance:


title: Nonprofit organization

text: Some of the above must be (in most jurisdictions in the USA at least) expressed in the organization's charter of establishment or constitution. Others may be provided by the supervising authority at each particular jurisdiction.


title: Nonprofit organization

text: While affiliations will not affect a legal status, they may be taken into consideration by legal proceedings as an indication of purpose. Most countries have laws that regulate the establishment and management of NPOs and that require compliance with corporate governance regimes. Most larger organizations are required to publish their financial reports detailing their income and expenditure publicly.


title: Nonprofit organization

text: In many aspects, they are similar to corporate business entities though there are often significant differences. Both not-for-profit and for-profit corporate entities must have board members, steering-committee members, or trustees who owe the organization a fiduciary duty of loyalty and trust. A notable exception to this involves churches, which are often not required to disclose finances to anyone, including church members.


title: Nonprofit organization

text: In the United States, nonprofit organizations are formed by filing bylaws or articles of incorporation or both in the state in which they expect to operate. The act of incorporation creates a legal entity enabling the organization to be treated as a distinct body (corporation) by law and to enter into business dealings, form contracts, and own property as individuals or for-profit corporations can.


title: Nonprofit organization

text: Nonprofits can have members, but many do not. The nonprofit may also be a trust or association of members. The organization may be controlled by its members who elect the board of directors, board of governors or board of trustees. A nonprofit may have a delegate structure to allow for the representation of groups or corporations as members. Alternatively, it may be a non-membership organization and the board of directors may elect its own successors.


title: Nonprofit organization

text: The two major types of nonprofit organization are membership and board-only. A membership organization elects the board and has regular meetings and the power to amend the bylaws. A board-only organization typically has a self-selected board and a membership whose powers are limited to those delegated to it by the board. A board-only organization's bylaws may even state that the organization does not have any membership, although the organization's literature may refer to its donors or service recipients as 'members'; examples of such organizations are FairVote and the National Organization for the Reform of Marijuana Laws. The Model Nonprofit Corporation Act imposes many complexities and requirements on membership decision-making. Accordingly, many organizations, such as the Wikimedia Foundation, have formed board-only structures. The National Association of Parliamentarians has generated concerns about the implications of this trend for the future of openness, accountability, and understanding of public concerns in nonprofit organizations. Specifically, they note that nonprofit organizations, unlike business corporations, are not subject to market discipline for products and shareholder discipline of their capital; therefore, without membership control of major decisions such as the election of the board, there are few inherent safeguards against abuse. A rebuttal to this might be that as nonprofit organizations grow and seek larger donations, the degree of scrutiny increases, including expectations of audited financial statements. A further rebuttal might be that NPOs are constrained, by their choice of legal structure, from financial benefit as far as distribution of profit to members and directors is concerned.


title: Nonprofit organization

text: In many countries, nonprofits may apply for tax-exempt status, so that the organization itself may be exempt from income tax and other taxes. In the United States, to be exempt from federal income taxes, the organization must meet the requirements set forth in the Internal Revenue Code (IRC). Granting nonprofit status is done by the state, while granting tax-exempt designation (such as IRC 501(c)) is granted by the federal government via the IRS. This means that not all nonprofits are eligible to be tax-exempt. For example, employees of non-profit organizations pay taxes from their salaries, which they receive according to the laws of the country. NPOs use the model of a double bottom line in that furthering their cause is more important than making a profit, though both are needed to ensure the organization's sustainability. An advantage of non-profit organisations registered in the UK is that they benefit from some reliefs and exemptions. Charities and non-profits are exempt from Corporation Tax as well as the trustees being exempt from Income Tax.


title: Nonprofit organization

text: In the U.S., "social welfare" nonprofits (IRS Section 501(c)(4)) are frequently used by politicians. Their use has resulted in controversies for politicians such as Kwame Kilpatrick and Gretchen Whitmer.


title: Nonprofit organization

text: Founder's syndrome is an issue organizations experience as they expand. Dynamic founders, who have a strong vision of how to operate the project, try to retain control of the organization, even as new employees or volunteers want to expand the project's scope or change policy.


title: Nonprofit organization

text: Resource mismanagement is a particular problem with NPOs because the employees are not accountable to anyone who has a direct stake in the organization. For example, an employee may start a new program without disclosing its complete liabilities. The employee may be rewarded for improving the NPO's reputation, making other employees happy, and attracting new donors. Liabilities promised on the full faith and credit of the organization but not recorded anywhere constitute accounting fraud. But even indirect liabilities negatively affect the financial sustainability of the NPO, and the NPO will have financial problems unless strict controls are instated. Some commenters have argued that the receipt of significant funding from large for-profit corporations can ultimately alter the NPO's functions. A frequent measure of an NPO's efficiency is its expense ratio (i.e. expenditures on things other than its programs, divided by its total expenditures).


title: Nonprofit organization

text: Competition for employees with the public and private sector is another problem that nonprofit organizations inevitably face, particularly for management positions. There are reports of major talent shortages in the nonprofit sector today regarding newly graduated workers, and NPOs have for too long relegated hiring to a secondary priority, which could be why they find themselves in the position many do. While many established NPOs are well-funded and comparative to their public sector competitors, many more are independent and must be creative with which incentives they use to attract and maintain vibrant personalities. The initial interest for many is the remuneration package, though many who have been questioned after leaving an NPO have reported that it was stressful work environments and implacable work that drove them away.


title: Nonprofit organization

text: Public- and private-sector employment have, for the most part, been able to offer more to their employees than most nonprofit agencies throughout history. Either in the form of higher wages, more comprehensive benefit packages, or less tedious work, the public and private sectors have enjoyed an advantage over NPOs in attracting employees. Traditionally, the NPO has attracted mission-driven individuals who want to assist their chosen cause. Compounding the issue is that some NPOs do not operate in a manner similar to most businesses, or only seasonally. This leads many young and driven employees to forego NPOs in favor of more stable employment. Today, however, nonprofit organizations are adopting methods used by their competitors and finding new means to retain their employees and attract the best of the newly minted workforce.


title: Nonprofit organization

text: It has been mentioned that most nonprofits will never be able to match the pay of the private sector and therefore should focus their attention on benefits packages, incentives and implementing pleasurable work environments. A good environment is ranked higher than salary and pressure of work. NPOs are encouraged to pay as much as they are able and offer a low-stress work environment that the employee can associate him or herself positively with. Other incentives that should be implemented are generous vacation allowances or flexible work hours.


title: Nonprofit organization

text: When selecting a domain name, NPOs often use .org, or the country code top-level domain of their respective country, or the .edu top-level domain (TLD), to differentiate themselves from more commercial entities, which typically use .com.


title: Nonprofit organization

text: In the traditional domain noted in , .org is for "organizations that didn't fit anywhere else" in the naming system, which implies that it is the proper category for non-commercial organizations if they are not governmental, educational, or one of the other types with a specific TLD. It is not designated specifically for charitable organizations or any specific organizational or tax-law status, but encompasses anything that is not classifiable as another category. Currently, no restrictions are enforced on registration of .com or .org, so one can find organizations of all sorts in either of those domains, as well as other top-level domains including newer, more specific ones which may apply to particular sorts of organization including .museum for museums and .coop for cooperatives. Organizations might also register by the appropriate country code top-level domain for their country.


title: Nonprofit organization

text: Instead of being defined by 'non' words, some organizations are suggesting new, positive-sounding terminology to describe the sector. The term 'civil society organization' (CSO) has been used by a growing number of organizations, including the "Center for the Study of Global Governance". The term 'citizen sector organization' (CSO) has also been advocated to describe the sector – as one of citizens, for citizens – by organizations including . Advocates argue that these terms describe the sector in its own terms, without relying on terminology used for the government or business sectors. However, use of terminology by a nonprofit of self-descriptive language that is not legally compliant risks confusing the public about nonprofit abilities, capabilities, and limitations.


title: Benjamin Millepied

text: Benjamin Millepied (; born 10 June 1977) is a French dancer and choreographer, who has lived and worked in the United States since joining the New York City Ballet in 1995, where he became a soloist in 1998 and a principal in 2002. He has also created choreography for the company, and choreographed pieces for other major companies. He retired from the NYCB in 2011.


title: Benjamin Millepied

text: He initiated the LA Dance Project, leading it from 2011 to 2014. The Chesta Tony project in Mobile Alabama was a project that was never finished due to the pandemic. He was Director of Dance at the Paris Opera Ballet from October 2014 and resigned in 2016. He is known for his work in the movie "Black Swan" (2010), which he choreographed, and in which he starred as a dancer, and for choregraphing the "sandwalk" in "Dune".


title: Benjamin Millepied

text: Millepied was born in Bordeaux, France. He is the youngest of three sons. His ballet training started at the age of eight with his mother, Catherine Flory, a former ballet dancer. His father is Denys Millepied. Between the ages of 13 and 16, he studied with Michel Rahn at the "Conservatoire National" in Lyon, France.


title: Benjamin Millepied

text: In the summer of 1992 Millepied attended classes at the School of American Ballet (SAB) and returned to study full-time in 1993, with a scholarship from the French Ministry ("Bourse Lavoisier" or Lavoisier Scholarship). Early in his career, Millepied was mentored by choreographer Jerome Robbins, who took an interest in him. At SAB's 1994 Spring Workshop he originated a principal role in Jerome Robbins' premiere of "2 and 3 Part Inventions" and also received the Prix de Lausanne.


title: Benjamin Millepied

text: Millepied joined New York City Ballet's corps de ballet in 1995, was promoted to soloist in 1998 and became principal dancer in 2002.


title: Benjamin Millepied

text: Millepied also became a choreographer, creating dances for City Ballet, American Ballet Theatre, the School of American Ballet, the Metropolitan Opera, the Paris Opera Ballet, Ballet de Genève, and his own company, Danses Concertantes. From 2006 to 2007, he was choreographer-in-residence at the Baryshnikov Arts Center in New York.


title: Benjamin Millepied

text: In 2011, L.A. Dance Project, founded and directed by Millepied, was launched with a commission, expected to last two years, from Glorya Kaufman Presents Dance at the Los Angeles Music Center. The company's operating budget is about $1 million a year. Millepied partnered with composer Nico Muhly, producer Charles Fabius, composer Nicholas Britell, and Matthieu Humery to found the company. In 2012, L.A. Dance Project established a full-time residence at Los Angeles Theatre Center with the objective of presenting new works throughout the city. L.A. Dance Project's inaugural performance, commissioned by The Music Center was held at Walt Disney Concert Hall on 22 September 2012.


title: Benjamin Millepied

text: Later that year, Millepied and L.A. Dance Project dancer Amanda Wells performed a 30-minute duet entitled "Framework" at the Museum of Contemporary Art. The dance collective's first program featured a Millepied premiere, "Moving Parts", with a score by Muhly and visual design by painter Christopher Wool. The program also includes a revival of Merce Cunningham's 1964 "Winterbranch", a movement exploration of falling bodies set to a mostly two-note score by La Monte Young, and William Forsythe's "Quintett", a 1993 study in loss and hope to avant-garde composer Gavin Bryar's composition "Jesus' Blood Never Failed Me Yet". Millepied's collaborators include Rodarte, Barbara Kruger, and Alex Israel, a contemporary California painter and video artist.


title: Benjamin Millepied

text: The premiere of "Reflections" by Millepied took place at Theatre du Chatelet in Paris on 23 April 2013. In 2013, L.A. Dance Project continued to tour at the Holland Festival in Amsterdam, Istanbul, Spoleto Festival in Italy, Edinburgh International Festival, La Maison de la Danse in Lyon, France and Sadler's Wells Theatre in London. In September 2013, at Maison de la Danse in Lyon, the company premiered two new pieces. The first premiere was "Murder Ballads", choreographed by Justin Peck with music by Bryce Dessner. Next on the program was the premiere of "Morgan's Last Chug" choreographed and with light and sound design by Emanuel Gat.


title: Benjamin Millepied

text: In January 2014, L.A. Dance Project announced that its new home venue would be the Theatre at Ace Hotel. By June 2016, L.A. Dance Project formed a three-year partnership with the LUMA Foundation in Arles, France, offering the nine-member company a continuing residency and performance space in the foundation's Parc des Ateliers. L.A. Dance Project will spend five non-consecutive weeks a year in Arles, where the company will be able to work, create and produce.


title: Benjamin Millepied

text: In January 2013, the Paris Opera Ballet announced that Millepied had accepted the position of director of dance. He officially succeeded Brigitte Lefèvre on 15 October 2014.


title: Benjamin Millepied

text: During his time at the Paris Opera Ballet, Millepied brought in William Forsythe as an associate choreographer and collaborator on the new Academy, an in-house training program for choreographers. Millepied's first season opened with a celebrity-filled gala that raised over a million euros. He also established a digital platform for new work and organized dancer exchanges with the Mariinsky and American Ballet Theater.


title: Benjamin Millepied

text: "Relève", a ballet documentary by Thierry Demaizière and Alban Teurlai featuring Millepied as he mounts his first production as director of the Paris ballet, premiered in France on "Canal+" in December 2015. As "Reset", it later had its North American premiere at the Tribeca Film Festival.


title: Benjamin Millepied

text: Millepied resigned from the Paris Opera Ballet on 4 February 2016 and was succeeded by Aurélie Dupont.


title: Benjamin Millepied

text: Millepied has commissioned and collaborated with contemporary composers including David Lang, Nico Muhly, Thierry Escaich, Daniel Ott, and Philip Glass. The Jerome Robbins Trust and Foundation has underwritten Millepied's work and donors include philanthropists Anne Bass and Arlene Cooper.


title: Benjamin Millepied

text: In 2001, Millepied's dancing was motion-captured for the animated children's film "Barbie in the Nutcracker", along with that of other New York City Ballet dancers. His dancing was again captured for the 2003 Barbie film "Barbie of Swan Lake".


title: Benjamin Millepied

text: In 2009, he served as choreographer for "Black Swan", a psychological thriller directed by Darren Aronofsky which stars Natalie Portman and Mila Kunis as ballet dancers in New York City. He also danced and appeared in the film. In 2010, he was the leading man in a short film co-directed by Asa Mader and starring Léa Seydoux, called "Time Doesn't Stand Still".


title: Benjamin Millepied

text: In 2012, Millepied founded The Amoveo Company, a multimedia production company and art collective. He has directed a number of short films in collaboration with various artists, including Mark Bradford, Philip Glass, IO Echo, Zeds Dead, and Lil Buck.


title: Benjamin Millepied

text: On the invitation of Los Angeles Music Center board member and TV host Nigel Lythgoe, Millepied was a guest judge on the dance competition show "So You Think You Can Dance" on 22 August 2012.


title: Benjamin Millepied

text: In 2014, Millepied became the Artistic Advisor of the new Dance Academy at the Colburn School in Downtown Los Angeles, joining fellow former-principal dancers with the New York City Ballet, Jenifer Ringer and James Fayette.


title: Benjamin Millepied

text: In 1994, he received the Prix de Lausanne and the next year, he was the recipient of the Mae L. Wien Award for Outstanding Promise.


title: Benjamin Millepied

text: Millepied met actress Natalie Portman on the set of "Black Swan" in early 2009 and reportedly left his live-in girlfriend at the time, Isabella Boylston, a principal dancer at the American Ballet Theatre, to begin a relationship with Portman. Millepied and Portman wed in a Jewish ceremony held in Big Sur, California on 4 August 2012. The family lived in Paris for a time, after Millepied accepted the position of director of dance with the Paris Opera Ballet. They have two children: a son Aleph (b. 2011) and a daughter Amalia (b. 2017). In January 2014, Millepied said he was in the process of converting to Judaism (his wife's faith). In 2016, the family moved from Paris to Los Angeles.


title: Hemoglobin

text: Hemoglobin (haemoglobin BrE) (from the Greek word αἷμα, "haîma" 'blood' + Latin "globus" 'ball, sphere' + "-in") (), abbreviated Hb or Hgb, is the iron-containing oxygen-transport metalloprotein present in red blood cells (erythrocytes) of almost all vertebrates (the exception being the fish family Channichthyidae) as well as the tissues of some invertebrates. Hemoglobin in blood carries oxygen from the respiratory organs ("e.g." lungs or gills) to the rest of the body ("i.e." tissues). There it releases the oxygen to permit aerobic respiration to provide energy to power functions of an organism in the process called metabolism. A healthy individual human has 12to 20grams of hemoglobin in every 100mL of blood.


title: Hemoglobin

text: In mammals, the chromoprotein makes up about 96% of the red blood cells' dry content (by weight), and around 35% of the total content (including water). Hemoglobin has an oxygen-binding capacity of 1.34mL O per gram, which increases the total blood oxygen capacity seventy-fold compared to dissolved oxygen in blood. The mammalian hemoglobin molecule can bind (carry) up to four oxygen molecules.


title: Hemoglobin

text: Hemoglobin is involved in the transport of other gases: It carries some of the body's respiratory carbon dioxide (about 20–25% of the total) as carbaminohemoglobin, in which CO is bound to the heme protein. The molecule also carries the important regulatory molecule nitric oxide bound to a thiol group in the globin protein, releasing it at the same time as oxygen.


title: Hemoglobin

text: Hemoglobin is also found outside red blood cells and their progenitor lines. Other cells that contain hemoglobin include the A9 dopaminergic neurons in the substantia nigra, macrophages, alveolar cells, lungs, retinal pigment epithelium, hepatocytes, mesangial cells in the kidney, endometrial cells, cervical cells and vaginal epithelial cells. In these tissues, hemoglobin has a non-oxygen-carrying function as an antioxidant and a regulator of iron metabolism. Excessive glucose in one's blood can attach to hemoglobin and raise the level of hemoglobin A1c.


title: Hemoglobin

text: Hemoglobin and hemoglobin-like molecules are also found in many invertebrates, fungi, and plants. In these organisms, hemoglobins may carry oxygen, or they may act to transport and regulate other small molecules and ions such as carbon dioxide, nitric oxide, hydrogen sulfide and sulfide. A variant of the molecule, called leghemoglobin, is used to scavenge oxygen away from anaerobic systems, such as the nitrogen-fixing nodules of leguminous plants, lest the oxygen poison (deactivate) the system.


title: Hemoglobin

text: Hemoglobinemia is a medical condition in which there is an excess of hemoglobin in the blood plasma. This is an effect of intravascular hemolysis, in which hemoglobin separates from red blood cells, a form of anemia.


title: Hemoglobin

text: In 1825, Johann Friedrich Engelhart discovered that the ratio of iron to protein is identical in the hemoglobins of several species. From the known atomic mass of iron he calculated the molecular mass of hemoglobin to "n" × 16000 ("n" = number of iron atoms per hemoglobin, now known to be 4), the first determination of a protein's molecular mass. This "hasty conclusion" drew a lot of ridicule at the time from scientists who could not believe that any molecule could be that big. Gilbert Smithson Adair confirmed Engelhart's results in 1925 by measuring the osmotic pressure of hemoglobin solutions.


title: Hemoglobin

text: Although blood had been known to carry oxygen since at least 1794, the oxygen-carrying property of hemoglobin was described by Hünefeld in 1840. In 1851, German physiologist Otto Funke published a series of articles in which he described growing hemoglobin crystals by successively diluting red blood cells with a solvent such as pure water, alcohol or ether, followed by slow evaporation of the solvent from the resulting protein solution. Hemoglobin's reversible oxygenation was described a few years later by Felix Hoppe-Seyler.


title: Hemoglobin

text: With the development of X-ray crystallography, it became possible to sequence protein structures. In 1959, Max Perutz determined the molecular structure of hemoglobin. For this work he shared the 1962 Nobel Prize in Chemistry with John Kendrew, who sequenced the globular protein myoglobin.


title: Hemoglobin

text: The name "hemoglobin" is derived from the words "heme" and "globin", reflecting the fact that each subunit of hemoglobin is a globular protein with an embedded heme group. Each heme group contains one iron atom, that can bind one oxygen molecule through ion-induced dipole forces. The most common type of hemoglobin in mammals contains four such subunits.


title: Hemoglobin

text: Hemoglobin consists of protein subunits (the globin molecules), and these proteins, in turn, are folded chains of a large number of different amino acids called polypeptides. The amino acid sequence of any polypeptide created by a cell is in turn determined by the stretches of DNA called genes. In all proteins, it is the amino acid sequence that determines the protein's chemical properties and function.


title: Hemoglobin

text: There is more than one hemoglobin gene: in humans, hemoglobin A (the main form of hemoglobin present in adults) is coded for by the genes, "HBA1", "HBA2", and "HBB". The hemoglobin subunit alpha 1 and alpha 2 are coded by the genes "HBA1" and "HBA2", respectively, which are both on chromosome 16 and are close to each other. The hemoglobin subunit beta is coded by "HBB" gene which is on chromosome 11 . The amino acid sequences of the globin proteins in hemoglobins usually differ between species. These differences grow with evolutionary distance between species. For example, the most common hemoglobin sequences in humans, bonobos and chimpanzees are completely identical, without even a single amino acid difference in either the alpha or the beta globin protein chains. Whereas the human and gorilla hemoglobin differ in one amino acid in both alpha and beta chains, these differences grow larger between less closely related species.


title: Hemoglobin

text: Even within species, variants of hemoglobin exist, although one sequence is usually "most common" in each species. Mutations in the genes for the hemoglobin protein in a species result in hemoglobin variants. Many of these mutant forms of hemoglobin cause no disease. Some of these mutant forms of hemoglobin, however, cause a group of hereditary diseases termed the "hemoglobinopathies". The best known hemoglobinopathy is sickle-cell disease, which was the first human disease whose mechanism was understood at the molecular level. A (mostly) separate set of diseases called thalassemias involves underproduction of normal and sometimes abnormal hemoglobins, through problems and mutations in globin gene regulation. All these diseases produce anemia.


title: Hemoglobin

text: Variations in hemoglobin amino acid sequences, as with other proteins, may be adaptive. For example, hemoglobin has been found to adapt in different ways to high altitudes. Organisms living at high elevations experience lower partial pressures of oxygen compared to those at sea level. This presents a challenge to the organisms that inhabit such environments because hemoglobin, which normally binds oxygen at high partial pressures of oxygen, must be able to bind oxygen when it is present at a lower pressure. Different organisms have adapted to such a challenge. For example, recent studies have suggested genetic variants in deer mice that help explain how deer mice that live in the mountains are able to survive in the thin air that accompanies high altitudes. A researcher from the University of Nebraska-Lincoln found mutations in four different genes that can account for differences between deer mice that live in lowland prairies versus the mountains. After examining wild mice captured from both highlands and lowlands, it was found that: the genes of the two breeds are "virtually identical—except for those that govern the oxygen-carrying capacity of their hemoglobin". "The genetic difference enables highland mice to make more efficient use of their oxygen", since less is available at higher altitudes, such as those in the mountains. Mammoth hemoglobin featured mutations that allowed for oxygen delivery at lower temperatures, thus enabling mammoths to migrate to higher latitudes during the Pleistocene. This was also found in hummingbirds that inhabit the Andes. Hummingbirds already expend a lot of energy and thus have high oxygen demands and yet Andean hummingbirds have been found to thrive in high altitudes. Non-synonymous mutations in the hemoglobin gene of multiple species living at high elevations ("Oreotrochilus, A. castelnaudii, C. violifer, P. gigas," and "A. viridicuada") have caused the protein to have less of an affinity for inositol hexaphosphate (IHP), a molecule found in birds that has a similar role as 2,3-BPG in humans; this results in the ability to bind oxygen in lower partial pressures.


title: Hemoglobin

text: Birds' unique circulatory lungs also promote efficient use of oxygen at low partial pressures of O. These two adaptations reinforce each other and account for birds' remarkable high-altitude performance.


title: Hemoglobin

text: Hemoglobin adaptation extends to humans, as well. There is a higher offspring survival rate among Tibetan women with high oxygen saturation genotypes residing at 4,000 m. Natural selection seems to be the main force working on this gene because the mortality rate of offspring is significantly lower for women with higher hemoglobin-oxygen affinity when compared to the mortality rate of offspring from women with low hemoglobin-oxygen affinity. While the exact genotype and mechanism by which this occurs is not yet clear, selection is acting on these women's ability to bind oxygen in low partial pressures, which overall allows them to better sustain crucial metabolic processes.


title: Hemoglobin

text: Hemoglobin (Hb) is synthesized in a complex series of steps. The heme part is synthesized in a series of steps in the mitochondria and the cytosol of immature red blood cells, while the globin protein parts are synthesized by ribosomes in the cytosol. Production of Hb continues in the cell throughout its early development from the proerythroblast to the reticulocyte in the bone marrow. At this point, the nucleus is lost in mammalian red blood cells, but not in birds and many other species. Even after the loss of the nucleus in mammals, residual ribosomal RNA allows further synthesis of Hb until the reticulocyte loses its RNA soon after entering the vasculature (this hemoglobin-synthetic RNA in fact gives the reticulocyte its reticulated appearance and name).


title: Hemoglobin

text: Hemoglobin has a quaternary structure characteristic of many multi-subunit globular proteins. Most of the amino acids in hemoglobin form alpha helices, and these helices are connected by short non-helical segments. Hydrogen bonds stabilize the helical sections inside this protein, causing attractions within the molecule, which then causes each polypeptide chain to fold into a specific shape. Hemoglobin's quaternary structure comes from its four subunits in roughly a tetrahedral arrangement.


title: Hemoglobin

text: In most vertebrates, the hemoglobin molecule is an assembly of four globular protein subunits. Each subunit is composed of a protein chain tightly associated with a non-protein prosthetic heme group. Each protein chain arranges into a set of alpha-helix structural segments connected together in a globin fold arrangement. Such a name is given because this arrangement is the same folding motif used in other heme/globin proteins such as myoglobin. This folding pattern contains a pocket that strongly binds the heme group.


title: Hemoglobin

text: A heme group consists of an iron (Fe) ion held in a heterocyclic ring, known as a porphyrin. This porphyrin ring consists of four pyrrole molecules cyclically linked together (by methine bridges) with the iron ion bound in the center. The iron ion, which is the site of oxygen binding, coordinates with the four nitrogen atoms in the center of the ring, which all lie in one plane. The heme is bound strongly (covalently) to the globular protein via the N atoms of the imidazole ring of F8 histidine residue (also known as the proximal histidine) below the porphyrin ring. A sixth position can reversibly bind oxygen by a coordinate covalent bond, completing the octahedral group of six ligands. This reversible bonding with oxygen is why hemoglobin is so useful for transporting oxygen around the body. Oxygen binds in an "end-on bent" geometry where one oxygen atom binds to Fe and the other protrudes at an angle. When oxygen is not bound, a very weakly bonded water molecule fills the site, forming a distorted octahedron.


title: Hemoglobin

text: Even though carbon dioxide is carried by hemoglobin, it does not compete with oxygen for the iron-binding positions but is bound to the amine groups of the protein chains attached to the heme groups.


title: Hemoglobin

text: The iron ion may be either in the ferrous Fe or in the ferric Fe state, but ferrihemoglobin (methemoglobin) (Fe) cannot bind oxygen. In binding, oxygen temporarily and reversibly oxidizes (Fe) to (Fe) while oxygen temporarily turns into the superoxide ion, thus iron must exist in the +2 oxidation state to bind oxygen. If superoxide ion associated to Fe is protonated, the hemoglobin iron will remain oxidized and incapable of binding oxygen. In such cases, the enzyme methemoglobin reductase will be able to eventually reactivate methemoglobin by reducing the iron center.


title: Hemoglobin

text: In adult humans, the most common hemoglobin type is a tetramer (which contains four subunit proteins) called "hemoglobin A", consisting of two α and two β subunits non-covalently bound, each made of 141 and 146 amino acid residues, respectively. This is denoted as αβ. The subunits are structurally similar and about the same size. Each subunit has a molecular weight of about 16,000 daltons, for a total molecular weight of the tetramer of about 64,000 daltons (64,458 g/mol). Thus, 1 g/dL = 0.1551 mmol/L. Hemoglobin A is the most intensively studied of the hemoglobin molecules.


title: Hemoglobin

text: In human infants, the hemoglobin molecule is made up of 2 α chains and 2 γ chains. The γ chains are gradually replaced by β chains as the infant grows.


title: Hemoglobin

text: The four polypeptide chains are bound to each other by salt bridges, hydrogen bonds, and the hydrophobic effect.


title: Hemoglobin

text: In general, hemoglobin can be saturated with oxygen molecules (oxyhemoglobin), or desaturated with oxygen molecules (deoxyhemoglobin).


title: Hemoglobin

text: "Oxyhemoglobin" is formed during physiological respiration when oxygen binds to the heme component of the protein hemoglobin in red blood cells. This process occurs in the pulmonary capillaries adjacent to the alveoli of the lungs. The oxygen then travels through the blood stream to be dropped off at cells where it is utilized as a terminal electron acceptor in the production of ATP by the process of oxidative phosphorylation. It does not, however, help to counteract a decrease in blood pH. Ventilation, or breathing, may reverse this condition by removal of carbon dioxide, thus causing a shift up in pH.


title: Hemoglobin

text: Hemoglobin exists in two forms, a "taut (tense) form" (T) and a "relaxed form" (R). Various factors such as low pH, high CO and high 2,3 BPG at the level of the tissues favor the taut form, which has low oxygen affinity and releases oxygen in the tissues. Conversely, a high pH, low CO, or low 2,3 BPG favors the relaxed form, which can better bind oxygen. The partial pressure of the system also affects O affinity where, at high partial pressures of oxygen (such as those present in the alveoli), the relaxed (high affinity, R) state is favoured. Inversely, at low partial pressures (such as those present in respiring tissues), the (low affinity, T) tense state is favoured. Additionally, the binding of oxygen to the iron(II) heme pulls the iron into the plane of the porphyrin ring, causing a slight conformational shift. The shift encourages oxygen to bind to the three remaining heme units within hemoglobin (thus, oxygen binding is cooperative).


title: Hemoglobin

text: Deoxygenated hemoglobin (deoxyhemoglobin) is the form of hemoglobin without the bound oxygen. The absorption spectra of oxyhemoglobin and deoxyhemoglobin differ. The oxyhemoglobin has significantly lower absorption of the 660 nm wavelength than deoxyhemoglobin, while at 940 nm its absorption is slightly higher. This difference is used for the measurement of the amount of oxygen in a patient's blood by an instrument called a pulse oximeter. This difference also accounts for the presentation of cyanosis, the blue to purplish color that tissues develop during hypoxia.


title: Hemoglobin

text: Deoxygenated hemoglobin is paramagnetic; it is weakly attracted to magnetic fields. In contrast, oxygenated hemoglobin exhibits diamagnetism, a weak repulsion from a magnetic field.


title: Hemoglobin

text: Scientists agree that the event that separated myoglobin from hemoglobin occurred after lampreys diverged from jawed vertebrates. This separation of myoglobin and hemoglobin allowed for the different functions of the two molecules to arise and develop: myoglobin has more to do with oxygen storage while hemoglobin is tasked with oxygen transport. The α- and β-like globin genes encode the individual subunits of the protein. The predecessors of these genes arose through another duplication event also after the gnathosome common ancestor derived from jawless fish, approximately 450–500 million years ago. Ancestral reconstruction studies suggest that the preduplication ancestor of the α and β genes was a dimer made up of identical globin subunits, which then evolved to assemble into a tetrameric architecture after the duplication. The development of α and β genes created the potential for hemoglobin to be composed of multiple distinct subunits, a physical composition central to hemoglobin's ability to transport oxygen. Having multiple subunits contributes to hemoglobin's ability to bind oxygen cooperatively as well as be regulated allosterically. Subsequently, the α gene also underwent a duplication event to form the "HBA1" and "HBA2" genes. These further duplications and divergences have created a diverse range of α- and β-like globin genes that are regulated so that certain forms occur at different stages of development.


title: Hemoglobin

text: Most ice fish of the family Channichthyidae have lost their hemoglobin genes as an adaptation to cold water.


title: Hemoglobin

text: Assigning oxygenated hemoglobin's oxidation state is difficult because oxyhemoglobin (Hb-O), by experimental measurement, is diamagnetic (no net unpaired electrons), yet the lowest-energy (ground-state) electron configurations in both oxygen and iron are paramagnetic (suggesting at least one unpaired electron in the complex). The lowest-energy form of oxygen, and the lowest energy forms of the relevant oxidation states of iron, are these:


title: Hemoglobin

text: All of these structures are paramagnetic (have unpaired electrons), not diamagnetic. Thus, a non-intuitive (e.g., a higher-energy for at least one species) distribution of electrons in the combination of iron and oxygen must exist, in order to explain the observed diamagnetism and no unpaired electrons.


title: Hemoglobin

text: Another possible model in which low-spin Fe binds to peroxide, O, can be ruled out by itself, because the iron is paramagnetic (although the peroxide ion is diamagnetic). Here, the iron has been oxidized by two electrons, and the oxygen reduced by two electrons.


title: Hemoglobin

text: Thus, the nearest formal oxidation state of iron in Hb-O is the +3 state, with oxygen in the −1 state (as superoxide .O). The diamagnetism in this configuration arises from the single unpaired electron on superoxide aligning antiferromagnetically with the single unpaired electron on iron (in a low-spin d state), to give no net spin to the entire configuration, in accordance with diamagnetic oxyhemoglobin from experiment.


title: Hemoglobin

text: The second choice of the logical possibilities above for diamagnetic oxyhemoglobin being found correct by experiment, is not surprising: singlet oxygen (possibility #1) is an unrealistically high energy state. Model 3 leads to unfavorable separation of charge (and does not agree with the magnetic data), although it could make a minor contribution as a resonance form. Iron's shift to a higher oxidation state in Hb-O decreases the atom's size, and allows it into the plane of the porphyrin ring, pulling on the coordinated histidine residue and initiating the allosteric changes seen in the globulins.


title: Hemoglobin

text: Early postulates by bio-inorganic chemists claimed that possibility #1 (above) was correct and that iron should exist in oxidation state II. This conclusion seemed likely, since the iron oxidation state III as methemoglobin, when "not" accompanied by superoxide .O to "hold" the oxidation electron, was known to render hemoglobin incapable of binding normal triplet O as it occurs in the air. It was thus assumed that iron remained as Fe(II) when oxygen gas was bound in the lungs. The iron chemistry in this previous classical model was elegant, but the required presence of the diamagnetic, high-energy, singlet oxygen molecule was never explained. It was classically argued that the binding of an oxygen molecule placed high-spin iron(II) in an octahedral field of strong-field ligands; this change in field would increase the crystal field splitting energy, causing iron's electrons to pair into the low-spin configuration, which would be diamagnetic in Fe(II). This forced low-spin pairing is indeed thought to happen in iron when oxygen binds, but is not enough to explain iron's change in size. Extraction of an additional electron from iron by oxygen is required to explain both iron's smaller size and observed increased oxidation state, and oxygen's weaker bond.


title: Hemoglobin

text: The assignment of a whole-number oxidation state is a formalism, as the covalent bonds are not required to have perfect bond orders involving whole electron transfer. Thus, all three models for paramagnetic Hb-O may contribute to some small degree (by resonance) to the actual electronic configuration of Hb-O. However, the model of iron in Hb-O being Fe(III) is more correct than the classical idea that it remains Fe(II).


title: Hemoglobin

text: When oxygen binds to the iron complex, it causes the iron atom to move back toward the center of the plane of the porphyrin ring (see moving diagram). At the same time, the imidazole side-chain of the histidine residue interacting at the other pole of the iron is pulled toward the porphyrin ring. This interaction forces the plane of the ring sideways toward the outside of the tetramer, and also induces a strain in the protein helix containing the histidine as it moves nearer to the iron atom. This strain is transmitted to the remaining three monomers in the tetramer, where it induces a similar conformational change in the other heme sites such that binding of oxygen to these sites becomes easier.


title: Hemoglobin

text: As oxygen binds to one monomer of hemoglobin, the tetramer's conformation shifts from the T (tense) state to the R (relaxed) state. This shift promotes the binding of oxygen to the remaining three monomer's heme groups, thus saturating the hemoglobin molecule with oxygen.


title: Hemoglobin

text: In the tetrameric form of normal adult hemoglobin, the binding of oxygen is, thus, a cooperative process. The binding affinity of hemoglobin for oxygen is increased by the oxygen saturation of the molecule, with the first molecules of oxygen bound influencing the shape of the binding sites for the next ones, in a way favorable for binding. This positive cooperative binding is achieved through steric conformational changes of the hemoglobin protein complex as discussed above; i.e., when one subunit protein in hemoglobin becomes oxygenated, a conformational or structural change in the whole complex is initiated, causing the other subunits to gain an increased affinity for oxygen. As a consequence, the oxygen binding curve of hemoglobin is sigmoidal, or "S"-shaped, as opposed to the normal hyperbolic curve associated with noncooperative binding.


title: Hemoglobin

text: The dynamic mechanism of the cooperativity in hemoglobin and its relation with low-frequency resonance has been discussed.


title: Hemoglobin

text: Besides the oxygen ligand, which binds to hemoglobin in a cooperative manner, hemoglobin ligands also include competitive inhibitors such as carbon monoxide (CO) and allosteric ligands such as carbon dioxide (CO) and nitric oxide (NO). The carbon dioxide is bound to amino groups of the globin proteins to form carbaminohemoglobin; this mechanism is thought to account for about 10% of carbon dioxide transport in mammals. Nitric oxide can also be transported by hemoglobin; it is bound to specific thiol groups in the globin protein to form an S-nitrosothiol, which dissociates into free nitric oxide and thiol again, as the hemoglobin releases oxygen from its heme site. This nitric oxide transport to peripheral tissues is hypothesized to assist oxygen transport in tissues, by releasing vasodilatory nitric oxide to tissues in which oxygen levels are low.


title: Hemoglobin

text: The binding of oxygen is affected by molecules such as carbon monoxide (for example, from tobacco smoking, exhaust gas, and incomplete combustion in furnaces). CO competes with oxygen at the heme binding site. Hemoglobin's binding affinity for CO is 250 times greater than its affinity for oxygen, meaning that small amounts of CO dramatically reduce hemoglobin's ability to deliver oxygen to the target tissue. Since carbon monoxide is a colorless, odorless and tasteless gas, and poses a potentially fatal threat, carbon monoxide detectors have become commercially available to warn of dangerous levels in residences. When hemoglobin combines with CO, it forms a very bright red compound called carboxyhemoglobin, which may cause the skin of CO poisoning victims to appear pink in death, instead of white or blue. When inspired air contains CO levels as low as 0.02%, headache and nausea occur; if the CO concentration is increased to 0.1%, unconsciousness will follow. In heavy smokers, up to 20% of the oxygen-active sites can be blocked by CO.


title: Hemoglobin

text: In similar fashion, hemoglobin also has competitive binding affinity for cyanide (CN), sulfur monoxide (SO), and sulfide (S), including hydrogen sulfide (HS). All of these bind to iron in heme without changing its oxidation state, but they nevertheless inhibit oxygen-binding, causing grave toxicity.


title: Hemoglobin

text: The iron atom in the heme group must initially be in the ferrous (Fe) oxidation state to support oxygen and other gases' binding and transport (it temporarily switches to ferric during the time oxygen is bound, as explained above). Initial oxidation to the ferric (Fe) state without oxygen converts hemoglobin into "hemiglobin" or methemoglobin, which cannot bind oxygen. Hemoglobin in normal red blood cells is protected by a reduction system to keep this from happening. Nitric oxide is capable of converting a small fraction of hemoglobin to methemoglobin in red blood cells. The latter reaction is a remnant activity of the more ancient nitric oxide dioxygenase function of globins.


title: Hemoglobin

text: Carbon "di"oxide occupies a different binding site on the hemoglobin. At tissues, where carbon dioxide concentration is higher, carbon dioxide binds to allosteric site of hemoglobin, facilitating unloading of oxygen from hemoglobin and ultimately its removal from the body after the oxygen has been released to tissues undergoing metabolism. This increased affinity for carbon dioxide by the venous blood is known as the Bohr effect. Through the enzyme carbonic anhydrase, carbon dioxide reacts with water to give carbonic acid, which decomposes into bicarbonate and protons:


title: Hemoglobin

text: Hence, blood with high carbon dioxide levels is also lower in pH (more acidic). Hemoglobin can bind protons and carbon dioxide, which causes a conformational change in the protein and facilitates the release of oxygen. Protons bind at various places on the protein, while carbon dioxide binds at the α-amino group. Carbon dioxide binds to hemoglobin and forms carbaminohemoglobin. This decrease in hemoglobin's affinity for oxygen by the binding of carbon dioxide and acid is known as the Bohr effect. The Bohr effect favors the T state rather than the R state. (shifts the O-saturation curve to the "right"). Conversely, when the carbon dioxide levels in the blood decrease (i.e., in the lung capillaries), carbon dioxide and protons are released from hemoglobin, increasing the oxygen affinity of the protein. A reduction in the total binding capacity of hemoglobin to oxygen (i.e. shifting the curve down, not just to the right) due to reduced pH is called the root effect. This is seen in bony fish.


title: Hemoglobin

text: It is necessary for hemoglobin to release the oxygen that it binds; if not, there is no point in binding it. The sigmoidal curve of hemoglobin makes it efficient in binding (taking up O in lungs), and efficient in unloading (unloading O in tissues).


title: Hemoglobin

text: In people acclimated to high altitudes, the concentration of 2,3-Bisphosphoglycerate (2,3-BPG) in the blood is increased, which allows these individuals to deliver a larger amount of oxygen to tissues under conditions of lower oxygen tension. This phenomenon, where molecule Y affects the binding of molecule X to a transport molecule Z, is called a "heterotropic" allosteric effect. Hemoglobin in organisms at high altitudes has also adapted such that it has less of an affinity for 2,3-BPG and so the protein will be shifted more towards its R state. In its R state, hemoglobin will bind oxygen more readily, thus allowing organisms to perform the necessary metabolic processes when oxygen is present at low partial pressures.


title: Hemoglobin

text: Animals other than humans use different molecules to bind to hemoglobin and change its O affinity under unfavorable conditions. Fish use both ATP and GTP. These bind to a phosphate "pocket" on the fish hemoglobin molecule, which stabilizes the tense state and therefore decreases oxygen affinity. GTP reduces hemoglobin oxygen affinity much more than ATP, which is thought to be due to an extra hydrogen bond formed that further stabilizes the tense state. Under hypoxic conditions, the concentration of both ATP and GTP is reduced in fish red blood cells to increase oxygen affinity.


title: Hemoglobin

text: A variant hemoglobin, called fetal hemoglobin (HbF, αγ), is found in the developing fetus, and binds oxygen with greater affinity than adult hemoglobin. This means that the oxygen binding curve for fetal hemoglobin is left-shifted (i.e., a higher percentage of hemoglobin has oxygen bound to it at lower oxygen tension), in comparison to that of adult hemoglobin. As a result, fetal blood in the placenta is able to take oxygen from maternal blood.


title: Hemoglobin

text: Hemoglobin also carries nitric oxide (NO) in the globin part of the molecule. This improves oxygen delivery in the periphery and contributes to the control of respiration. NO binds reversibly to a specific cysteine residue in globin; the binding depends on the state (R or T) of the hemoglobin. The resulting S-nitrosylated hemoglobin influences various NO-related activities such as the control of vascular resistance, blood pressure and respiration. NO is not released in the cytoplasm of red blood cells but transported out of them by an anion exchanger called AE1.


title: Hemoglobin

text: Hemoglobin variants are a part of the normal embryonic and fetal development. They may also be pathologic mutant forms of hemoglobin in a population, caused by variations in genetics. Some well-known hemoglobin variants, such as sickle-cell anemia, are responsible for diseases and are considered hemoglobinopathies. Other variants cause no detectable pathology, and are thus considered non-pathological variants.


title: Hemoglobin

text: When red blood cells reach the end of their life due to aging or defects, they are removed from the circulation by the phagocytic activity of macrophages in the spleen or the liver or hemolyze within the circulation. Free hemoglobin is then cleared from the circulation via the hemoglobin transporter CD163, which is exclusively expressed on monocytes or macrophages. Within these cells the hemoglobin molecule is broken up, and the iron gets recycled. This process also produces one molecule of carbon monoxide for every molecule of heme degraded. Heme degradation is the only natural source of carbon monoxide in the human body, and is responsible for the normal blood levels of carbon monoxide in people breathing normal air.


title: Hemoglobin

text: The other major final product of heme degradation is bilirubin. Increased levels of this chemical are detected in the blood if red blood cells are being destroyed more rapidly than usual. Improperly degraded hemoglobin protein or hemoglobin that has been released from the blood cells too rapidly can clog small blood vessels, especially the delicate blood filtering vessels of the kidneys, causing kidney damage. Iron is removed from heme and salvaged for later use, it is stored as hemosiderin or ferritin in tissues and transported in plasma by beta globulins as transferrins. When the porphyrin ring is broken up, the fragments are normally secreted as a yellow pigment called bilirubin, which is secreted into the intestines as bile. Intestines metabolise bilirubin into urobilinogen. Urobilinogen leaves the body in faeces, in a pigment called stercobilin. Globulin is metabolised into amino acids that are then released into circulation.


title: Hemoglobin

text: Hemoglobin deficiency can be caused either by a decreased amount of hemoglobin molecules, as in anemia, or by decreased ability of each molecule to bind oxygen at the same partial pressure of oxygen. Hemoglobinopathies (genetic defects resulting in abnormal structure of the hemoglobin molecule) may cause both. In any case, hemoglobin deficiency decreases blood oxygen-carrying capacity. Hemoglobin deficiency is, in general, strictly distinguished from hypoxemia, defined as decreased partial pressure of oxygen in blood, although both are causes of hypoxia (insufficient oxygen supply to tissues).


title: Hemoglobin

text: Other common causes of low hemoglobin include loss of blood, nutritional deficiency, bone marrow problems, chemotherapy, kidney failure, or abnormal hemoglobin (such as that of sickle-cell disease).


title: Hemoglobin

text: The ability of each hemoglobin molecule to carry oxygen is normally modified by altered blood pH or CO, causing an altered oxygen–hemoglobin dissociation curve. However, it can also be pathologically altered in, e.g., carbon monoxide poisoning.


title: Hemoglobin

text: Decrease of hemoglobin, with or without an absolute decrease of red blood cells, leads to symptoms of anemia. Anemia has many different causes, although iron deficiency and its resultant iron deficiency anemia are the most common causes in the Western world. As absence of iron decreases heme synthesis, red blood cells in iron deficiency anemia are "hypochromic" (lacking the red hemoglobin pigment) and "microcytic" (smaller than normal). Other anemias are rarer. In hemolysis (accelerated breakdown of red blood cells), associated jaundice is caused by the hemoglobin metabolite bilirubin, and the circulating hemoglobin can cause kidney failure.


title: Hemoglobin

text: Some mutations in the globin chain are associated with the hemoglobinopathies, such as sickle-cell disease and thalassemia. Other mutations, as discussed at the beginning of the article, are benign and are referred to merely as hemoglobin variants.


title: Hemoglobin

text: There is a group of genetic disorders, known as the "porphyrias" that are characterized by errors in metabolic pathways of heme synthesis. King George III of the United Kingdom was probably the most famous porphyria sufferer.


title: Hemoglobin

text: To a small extent, hemoglobin A slowly combines with glucose at the terminal valine (an alpha aminoacid) of each β chain. The resulting molecule is often referred to as Hb A, a glycated hemoglobin. The binding of glucose to amino acids in the hemoglobin takes place spontaneously (without the help of an enzyme) in many proteins, and is not known to serve a useful purpose. However, as the concentration of glucose in the blood increases, the percentage of Hb A that turns into Hb A increases. In diabetics whose glucose usually runs high, the percent Hb A also runs high. Because of the slow rate of Hb A combination with glucose, the Hb A percentage reflects a weighted average of blood glucose levels over the lifetime of red cells, which is approximately 120 days. The levels of glycated hemoglobin are therefore measured in order to monitor the long-term control of the chronic disease of type 2 diabetes mellitus (T2DM). Poor control of T2DM results in high levels of glycated hemoglobin in the red blood cells. The normal reference range is approximately 4.0–5.9%. Though difficult to obtain, values less than 7% are recommended for people with T2DM. Levels greater than 9% are associated with poor control of the glycated hemoglobin, and levels greater than 12% are associated with very poor control. Diabetics who keep their glycated hemoglobin levels close to 7% have a much better chance of avoiding the complications that may accompany diabetes (than those whose levels are 8% or higher). In addition, increased glycated of hemoglobin increases its affinity for oxygen, therefore preventing its release at the tissue and inducing a level of hypoxia in extreme cases.


title: Hemoglobin

text: Elevated levels of hemoglobin are associated with increased numbers or sizes of red blood cells, called polycythemia. This elevation may be caused by congenital heart disease, cor pulmonale, pulmonary fibrosis, too much erythropoietin, or polycythemia vera. High hemoglobin levels may also be caused by exposure to high altitudes, smoking, dehydration (artificially by concentrating Hb), advanced lung disease and certain tumors.


title: Hemoglobin

text: Hemoglobin concentration measurement is among the most commonly performed blood tests, usually as part of a complete blood count. For example, it is typically tested before or after blood donation. Results are reported in g/L, g/dL or mol/L. 1 g/dL equals about 0.6206 mmol/L, although the latter units are not used as often due to uncertainty regarding the polymeric state of the molecule. This conversion factor, using the single globin unit molecular weight of 16,000 Da, is more common for hemoglobin concentration in blood. For MCHC (mean corpuscular hemoglobin concentration) the conversion factor 0.155, which uses the tetramer weight of 64,500 Da, is more common. Normal levels are:


title: Hemoglobin

text: Normal values of hemoglobin in the 1st and 3rd trimesters of pregnant women must be at least 11 g/dL and at least 10.5 g/dL during the 2nd trimester.


title: Hemoglobin

text: Dehydration or hyperhydration can greatly influence measured hemoglobin levels. Albumin can indicate hydration status.


title: Hemoglobin

text: If the concentration is below normal, this is called anemia. Anemias are classified by the size of red blood cells, the cells that contain hemoglobin in vertebrates. The anemia is called "microcytic" if red cells are small, "macrocytic" if they are large, and "normocytic" otherwise.


title: Hemoglobin

text: Hematocrit, the proportion of blood volume occupied by red blood cells, is typically about three times the hemoglobin concentration measured in g/dL. For example, if the hemoglobin is measured at 17 g/dL, that compares with a hematocrit of 51%.


title: Hemoglobin

text: Laboratory hemoglobin test methods require a blood sample (arterial, venous, or capillary) and analysis on hematology analyzer and CO-oximeter. Additionally, a new noninvasive hemoglobin (SpHb) test method called Pulse CO-Oximetry is also available with comparable accuracy to invasive methods.


title: Hemoglobin

text: Concentrations of oxy- and deoxyhemoglobin can be measured continuously, regionally and noninvasively using NIRS. NIRS can be used both on the head and on muscles. This technique is often used for research in e.g. elite sports training, ergonomics, rehabilitation, patient monitoring, neonatal research, functional brain monitoring, brain–computer interface, urology (bladder contraction), neurology (Neurovascular coupling) and more.