Degradation of endogenous hepatic heme by pathways not yielding carbon monoxide. Studies in normal rat liver and in primary hepatocyte culture

Abstract

The conversion of endogenous hepatic heme to bilirubin and CO is established. However, it is unknown whether this process is quantitative or whether heme may be degraded to other products as well. To study this question, we administered the heme precursor, delta-amino-[5-14C]levulinic acid to rats in vivo. In liver, [14C]heme was predominately associated with microsomal cytochromes, and its degradation was examined over a period of 12--14 h; concurrently, excretion of labeled carbon monoxide 14CO by the animal was measured. After correction for 14CO derived from the breakdown of renal [14C]heme, the rate of heme degradation calculated from the 14CO excreted was substantially less than the rate of disappearance of hepatic [14C]heme measured directly. The discrepancy between actual loss of labeled heme from the liver and generation of labeled CO was confirmed by direct study of endogenous [14C]heme degradation in primary hepatocyte culture, in which only 25% of the labeled heme disappearing during the incubation was converted to 14CO. By contrast, cultured cells converted exogenous [14C]heme nearly quantitatively to 14CO. We conclude that heme associated with microsomal cytochromes in normal rat liver is degraded substantially by non-CO forming processes.