ABSTRACT
This chapter outlines the present state of knowledge of heme catabolism and bilirubin formation, particularly from a mechanistic standpoint. It is concerned primarily with the mechanism of formation of bilirubin both in vivo and in vitro. However, it would be wrong to imply thereby that bilirubin is the only bile pigment of importance in biological systems. In mammalian systems, heme carries out a wide range of vital reactions. A great deal of work both structural and metabolic has indicated that, in mammalian systems, all of the bilirubin produced is derived from degradation of protoheme. Sometimes this versatility leads to quite different, almost opposite, functions. The determination of the nature of the biliverdin isomers produced during coupled oxidation reactions has proved of primary importance in the understanding of the mechanism of heme degradation and in relating model systems to biological heme cleavage. The cleavage selectivity is determined at this stage, probably by steric effects of amino acid residues on the apoprotein.
