What makes our bodies sense sugar, fruit or aspartame as "sweet"? Taste scientist Robert Magolskee discusses research published this week in the Proceedings of the National Academy of Sciences into newly discovered pathways for detecting sweet flavors.
JOE PALCA, host: This is SCIENCE FRIDAY. I'm Joe Palca.</s>JOE PALCA, host: When you take a bite of cotton candy or chomp down on a grape, what goes on in the mouth that causes your brain to say sweet? Flavor components such as sweet, salty, sour, bitter and umami all have distinct pathways and taste-detecting cells, responding to different molecular components in a crunch of cracker or a slurp of soup.</s>JOE PALCA, host: Writing this week in the Proceedings of the National Academy of Sciences, researchers say they think they've found two new ways the body can detect sweetness in addition to the pathways scientists already knew about.</s>JOE PALCA, host: Joining me now to talk about this is Robert Margolskee, Margolskee, I'm sorry. He's a molecular neurobiologist at the Monell Chemical Senses Center in Philadelphia, Pennsylvania, and one of the authors of the report. Thanks for joining us, Dr. Margolskee.</s>Dr. ROBERT MARGOLSKEE (Molecular Neurobiologist, Monell Chemical Senses Center): Joe, it's a pleasure to be here.</s>JOE PALCA, host: And if you want to talk about sweetness, we're talking about the taste sweetness that is, 800-989-8255. That's 800-989-TALK. So what happens? I mean what's going on? We put something sweet in our mouth, and something responds to it. What is that?</s>Dr. ROBERT MARGOLSKEE (Molecular Neurobiologist, Monell Chemical Senses Center): Well, we've learned that sweet is a bit more complicated than we thought it was based on work over the past several years. And so our recent work makes it more complicated.</s>Dr. ROBERT MARGOLSKEE (Molecular Neurobiologist, Monell Chemical Senses Center): When you get a sweet substance, a sugar or something artificial like saccharine, it simulates these receptor proteins on the very outer tips of the sweet-responding taste cells. And we knew about that for a while...</s>JOE PALCA, host: So these are the taste buds?</s>Dr. ROBERT MARGOLSKEE (Molecular Neurobiologist, Monell Chemical Senses Center): These are taste cells right in the taste buds. So the taste bud contains about 50 or 100 taste cells, and maybe a quarter of them are responding to sweet stuff, and a different percentage of them will respond to salty and sour and bitter and something called umami, which is actually a Japanese word that has to do with delicious amino acids like monosodium glutamate.</s>JOE PALCA, host: Okay, and so this chemical interaction or biochemical interaction between the protein that makes the receptor on the surface of the taste bud, that's a chemical event. But something happens in the brain that makes this turn into a perception of an event or a sweetness event.</s>Dr. ROBERT MARGOLSKEE (Molecular Neurobiologist, Monell Chemical Senses Center): Correct. So you can think of the sweet receptor protein and the sugar or sweetener as kind of a lock and key, and when they encounter each other, it opens the lock. The door opens up. It excites the sweet taste cell, and that sends a signal to the brain, to particular centers of the central nervous system that respond to sweet.</s>Dr. ROBERT MARGOLSKEE (Molecular Neurobiologist, Monell Chemical Senses Center): And we thought we knew how that worked. But it turns out it's more complicated. And in particular for special types of sweet compounds, the ones we like the most, sucrose and glucose and fructose, the monosaccharide and disaccharide sweeteners, there are extra pathways, extra mechanisms that let us taste something like that as being sweet.</s>Dr. ROBERT MARGOLSKEE (Molecular Neurobiologist, Monell Chemical Senses Center): And these are, as we reported in this recent paper, sugar transporters and special ion channels, potassium ion channels, that respond to the metabolic state of the organism or the metabolic state of the taste cell.</s>Dr. ROBERT MARGOLSKEE (Molecular Neurobiologist, Monell Chemical Senses Center): And remarkably enough, these same things you'll find in other parts of your body, in the gut, in the stomach, small intestine and in the endocrine cells in the pancreas.</s>Dr. ROBERT MARGOLSKEE (Molecular Neurobiologist, Monell Chemical Senses Center): So we're finding that, at least, the sense of sweet taste has a lot in common with these endocrine or hormone-producing cells elsewhere in the body.</s>JOE PALCA, host: Wow. So if you injected a sugar substance into the pancreas, you wouldn't perceive the sense of having something sweet in your body, would you? It would be your pancreas would do something, or something would happen, but you wouldn't feel like you just had a sweet meal, or something.</s>Dr. ROBERT MARGOLSKEE (Molecular Neurobiologist, Monell Chemical Senses Center): Right. That's not something that we're generally consciously aware of, although you can actually train mice and rats to tell if they've gotten something sweet in their stomach or in their small intestine.</s>Dr. ROBERT MARGOLSKEE (Molecular Neurobiologist, Monell Chemical Senses Center): So you can bypass their taste buds in the oral cavity and directly put sugar into the stomach or small intestine, and those animals can be trained to know that that's something good and something positive, and they will seek more of that stimulus.</s>JOE PALCA, host: Wow, yeah, so the brain is overrated, I think is what we're saying here.</s>Dr. ROBERT MARGOLSKEE (Molecular Neurobiologist, Monell Chemical Senses Center): Well, there's a conscious level, and certainly the conscious level and appreciation of that rich piece of strawberry shortcake or cherry cheesecake is going to drive all sorts of processes consciously. And then when we not just visualize it but taste it, that will do even more. And then, finally, when it gets its way into the digestive tract, the sugars that are released there will stimulate special taste-like cells.</s>Dr. ROBERT MARGOLSKEE (Molecular Neurobiologist, Monell Chemical Senses Center): They'll put out hormones. They'll also send their signals to the brain, and it will just be an exquisite experience that wouldn't be enough with just the oral taste response unless you also had that response in your gut.</s>JOE PALCA, host: Interesting. All right, 800-989-8255. And let's take a call now from Roger(ph) in Raleigh, North Carolina. Roger, you're on the air. Thanks for calling.</s>ROGER (Caller): Hi, thank you. I was wondering if you could explain what happens if you put salt on something sour, and then it kind of tastes sweet. And also, I've always been amazed at how fast taste buds can repair themselves after you've burned them, like with hot coffee or something.</s>JOE PALCA, host: Interesting.</s>Dr. ROBERT MARGOLSKEE (Molecular Neurobiologist, Monell Chemical Senses Center): Okay, two very good questions. Let me start with the second one, about taste bud repair and taste bud turnover. The taste cells in the bud, they turn over pretty quickly. Their lifespan is about a week, maybe as long as 10 days.</s>Dr. ROBERT MARGOLSKEE (Molecular Neurobiologist, Monell Chemical Senses Center): So you have new taste cells being developed from precursor stem cells. They mature, and they differentiate into the salt responders, the sour responders, the sweet responders.</s>Dr. ROBERT MARGOLSKEE (Molecular Neurobiologist, Monell Chemical Senses Center): And then after a week or 10 days, they will die, and they'll turn over, and they'll be replaced. And this is one of those things, again, where the taste cells in the oral cavity do have some similarities to taste-like cells in the gut, which also will turn over in a few days, in a small number of days, up to a week or so.</s>Dr. ROBERT MARGOLSKEE (Molecular Neurobiologist, Monell Chemical Senses Center): Now, the first question, about the interaction of salt and sour and how that might be sweet, it's complicated. And on the one hand, some of this relates to our current work in this recent paper, in the Proceedings of the National Academy, where we have found a sugar transporter that likes to transport into the sweet taste cell, sugar, at the same time that it transports the sodium ion part of salt.</s>Dr. ROBERT MARGOLSKEE (Molecular Neurobiologist, Monell Chemical Senses Center): So we speculate - we don't know for sure, but we speculate - that if there's a little bit of salt around, that can make the sweet taste of sugar all that much sweeter. And in fact, if you take a very dilute solution of sodium chloride, table salt, so dilute that it doesn't taste salty, it actually tastes sweet.</s>Dr. ROBERT MARGOLSKEE (Molecular Neurobiologist, Monell Chemical Senses Center): And we're not 100 percent sure of how that works, but it could be stimulating the sweet taste proteins, or it could be stimulating this ion channel that we've found that's called STLT-1, sodium glucose co-transporter.</s>Dr. ROBERT MARGOLSKEE (Molecular Neurobiologist, Monell Chemical Senses Center): Now, the final point about the salt-sour interaction is this is something that psychophysicists, people that study the psychology and the perception of taste talk about as mixture suppression. So the salt detection mechanism and the sour detection mechanism are almost like they're talking at cross-purposes. Or the salt will block the sour channel, or the sour will block the salt channel.</s>Dr. ROBERT MARGOLSKEE (Molecular Neurobiologist, Monell Chemical Senses Center): So a certain amount of salt alone, or a certain amount of sour alone, will have a certain saltiness and sourness, but if you mix them together, it decreases both the saltiness and the sourness. And cooks know this, and people that like their salted margaritas know this, too.</s>JOE PALCA, host: Okay, very nice. Thanks, Roger. Let's take another call now from Esther(ph) in Ithaca, New York. Esther, you're on the air.</s>ESTHER (Caller): Hi. Last year, I heard a talk at the Cornell Plantations from a person who wrote a book called "The Fruit Hunters," and he talked about the miracle fruit, which is this interesting fruit where if you eat something sour first, like let's say you suck on a lime, and then you eat a little miracle fruit, what happens is your mouth fills with this incredible sweetness, and the sour taste of the lime just disappears. And he talked about how this was a way to get a taste of sweetness without any kind of sugar.</s>JOE PALCA, host: Did you try it, Esther?</s>ESTHER (Caller): I haven't tried it yet.</s>JOE PALCA, host: Oh, you should definitely...</s>ESTHER (Caller): I've been wanting to...</s>JOE PALCA, host: Yeah. You should definitely try it.</s>ESTHER (Caller): ...buy some online, but I haven't yet.</s>JOE PALCA, host: No. You should definitely try it if you get a chance. Dr. Magolskee, what's that about?</s>Dr. MAGOLSKEE: So that's fun to do. I've done that. And one time, I took the miracle fruit component - and it's called miraculin - and mixed it in with unflavored, sour yoghurt, and it tastes wonderfully sweet. So we have a pretty good idea of what's going on there.</s>Dr. MAGOLSKEE: Miraculin is a protein, and you find it in the miracle fruit. And there a number of other related proteins that can be found in special plants and berries, oftentimes in Africa. So in addition to miraculin, you have things called thaumatin, brazzein, monelin.</s>Dr. MAGOLSKEE: Now, those other proteins, they're intensely sweet on their own. They don't need acid or sour stimuli, and we know how they work. They will bind tightly to the sweet receptor protein. This is, again, this lock-and-key type of model.</s>Dr. MAGOLSKEE: Now, miraculin is a little bit special. It probably doesn't normally bind to the sweet receptor protein - or, at least, it doesn't bind in a way that will open up the lock. But at low pH, under acid conditions, either the miraculin adopts a particular conformation or the sweet receptor does, so that it's now perceived as sweet.</s>Dr. MAGOLSKEE: So it's not that miraculin is working on the sour channel, the sour taste cells or the sour responding taste nerves, it's tricking the sweet taste cells and the sweet-responding taste nerves to say there's something sweet out there.</s>JOE PALCA, host: Very strange experience. And it really - I've tried it, and you taste a piece of lemon, and it's like you're eating a sugar candy. And it's with lemon before - for sure, lemon, because you can test yourself beforehand. Very odd.</s>JOE PALCA, host: Other animals - I mean, do we all have sweet tooths? Are there some people who are born without the ability to taste sweetness, or animals that are born without that ability?</s>Dr. MAGOLSKEE: Well, that's a very interesting question, and, to my knowledge, all people can taste sweet, although there are wide ranges in the preference for sweet. But certainly, not all animals can taste sweet, and one prime example is the cat, the domestic cat.</s>Dr. MAGOLSKEE: Other scientists at Monell - Joe Brand and Gary Beauchamp and Peihua Jiang -have looked at the sweet receptor protein gene in the cat, and they found that it is a pseudogene. That means it's a non-functional, mutated gene. So the cat cannot make the functional sweet taste receptor protein and can't respond to sweet.</s>Dr. MAGOLSKEE: Now, a related protein is for this umami amino acid protein glutamate taste, and cats have a very good umami receptor. And, in fact, they probably devoted what humans would respond to sweet more towards umami amino acids and proteins.</s>JOE PALCA, host: They don't need to worry so much about leaving your chocolate cake out if the cat's around, as much as you do with the dog around.</s>Dr. MAGOLSKEE: That's right.</s>Dr. MAGOLSKEE: That's exactly right and...</s>JOE PALCA, host: We're talking - I'm sorry. We're talking about sweet-taste detectors with Dr. Robert Magolskee. I'm Joe Palca, and this is SCIENCE FRIDAY from NPR.</s>JOE PALCA, host: I'm sorry. We were - I interrupted you there. You were starting to say about dogs.</s>Dr. MAGOLSKEE: I - well, I was actually going to talk about a different animal: giant panda bears.</s>Dr. MAGOLSKEE: And they're kind of the flipside of cats. They have a mutated umami receptor, so they don't respond to the amino acids and the proteins. But they have a very good functioning sweet receptor, and they have almost as much of a sweet tooth as humans. So a lot of sweet compounds that humans like, giant pandas also like.</s>JOE PALCA, host: There you go. And they're easy - they're fun to work with, I guess.</s>JOE PALCA, host: Anyway, we've run out of time. Thanks for taking the time to talk with me today, Dr. Magolskee.</s>Dr. MAGOLSKEE: My pleasure.</s>JOE PALCA, host: He's a molecular micro - neurobiologist at the Monell Chemical Senses Center in Philadelphia, Pennsylvania.