Figure 1: Schematic illustration of the biosynthesis and
catabolism of heme. Rectangles indicate the enzymes involved in
heme metabolism. Heme molecules are synthesized from glycine and
succinyl Co-A via eight-stepped enzymatic reactions. ALA:
-aminolevulinic acid; PBG: porphobilinogen. Heme, thus formed,
is catabolized to biliverdin by the microsomal enzyme heme
oxygenase 1. Biliverdin is subsequently metabolized to bilirubin
by biliverdin reductase. ABC transporter ABCB6 is considered to
be responsible for the import of coproporphyrinogen III into
mitochondria, whereas ABCG2 transports porphyrins across the
plasma membrane to maintain intracellular porphyrin homeostasis.
ABCG2-mediated porphyrin transport can be inhibited by drugs,
such as protein kinase inhibitors, as shown in Figure 5.