Unconjugated
bilirubin (UCB), the principal mammalian
bile pigment, is the end product of
heme catabolism. Both belong to the superfamily of tetrapyrrolic compounds that serve multiple biological functions in animals and plants. Its six internal hydrogen bonds give UCB a unique structure responsible for its physico-chemical properties and biological effects. Like many weakly-polar, poorly-soluble compounds, UCB is transported in blood tightly bound to
albumin, with less than 0.01% of total
bilirubin circulating in an unbound form (free
bilirubin, Bf). This fraction governs the diffusion of UCB into tissues, and therefore Bf is responsible for both its beneficial and toxic effects on cells. Although, UCB was long thought to be a non-functional
waste product, recent studies have shown that the
antioxidant effects of mildly elevated serum
bilirubin levels, as well as activation of
heme oxygenase, may protect against diseases associated with oxidative stress, such as
atherosclerosis. By contrast, markedly elevated serum UCB levels may cause severe neurological damage, especially in neonates. The regulation of cellular UCB content, by its conjugation, oxidation, and export, are, therefore of paramount importance to cellular health.