Biliverdin reductase of guinea pig liver.

The biosynthesis of the heme portion of hemoglobin by animal tissues has been studied extensively (1). In contrast, relatively little is known about the enzymes participating in the initial steps of the pathway for heme catabolism. Thus, the reaction in which heme and globin are separated remains essentially obscure, although it is known that heme undergoes ring cleavage with liberation of carbon monoxide (2, 3) and an unidentified product. The latter is converted to biliverdin (3) which in turn is reduced to bilirubin. This reduction of the central methene bridge of biliverdin is illustrated in Fig. 1. In 1936, Lemberg and Wyndham (4) studied the enzymatic reduction of biliverdin by washings of guinea pig liver mince. They observed a gradual change in the color of the incubation medium from green to yellow. By means of a semiquantitative assay of reaction rate they found that “cozymase” stimulated the reaction and could be replaced by several intermediary metabolites of carbohydrate metabolism. The compounds producing greatest stimulation included lactate, ethanol, succinate, citrate, and acetaldehyde. The authors suggested that biliverdin was a nonspecific acceptor of electrons, similar to methylene blue, and that several hepatic dehydrogenases could catalyze its reduction. The present paper provides a detailed examination of the enzymatic reduction of biliverdin in mammalian tissues.l The enzyme, biliverdin reductase, has been partially purified from guinea pig liver and an investigation of its properties is reported. Contrary to the earlier studies (4), the present work indicates the reaction to be relatively specific.