Isotopic studies of the conversion of oxophlorins and their ferrihaems into bile pigments in the rat

Abstract

1. Tritiated oxymesoporphyrins and their ferrihaems were tested as possible intermediates in the catabolism of haemoglobin. The tritiated compounds were injected into rats with biliary fistulae and the incorporation of the isotope into bile, bile pigment, urine, faeces, liver, kidney and spleen was measured. 2. alpha-Oxymesoferrihaem was extensively converted into bile pigment and specifically to the expected mesobilirubin. 3. beta-Oxymesoferrihaem was poorly converted into bile pigment and was not converted into mesobiliverdin IXbeta. The latter was independently shown to be excreted rapidly in bile. 4. The free oxyporphyrins were also poor precursors of bile pigment, and alpha-oxymesoporphyrin competed with bilirubin for excretion by the liver. 5. By analogy with the results obtained with alpha-oxymesoferrihaem it is concluded that alpha-oxyprotoferrihaem is an intermediate in the catabolism of haemoglobin, undergoing further oxidation to bile pigment under the catalysis of an enzyme of definite specificity.

Biosynthesis of phycobilins

“…Oxygenated ferrous heme, a-meso-hydroxyheme, and a species absorbing at 688 nm that has been tentatively identified as a-verdoheme have been detected as intermediate reaction products (Figure 3). [47][48][49][50] Figures 4-6 show proposed reaction mechanisms for each of the three oxygenation steps catalyzed by heme oxygenase. Initially, Fe(III)-protoheme binds to heme oxygenase, where it is reduced to Fe(II)-protoheme by an electron provided by NADPH via NADPH-cytochrome c reductase.…”

Hemes, Chlorophylls, and Related Compounds: Biosynthesis and Metabolic Regulation

“…In the animal heme degradative pathway, the first identified intermediate is a-oxyheme ( Fig. 13) (201). We do not know the precise enzymatic nature of this reaction nor of the subsequent formation of biliverdin.…”

On the mechanism of the chemical and enzymic oxygenations of alpha-oxyprotohemin IX to Fe.biliverdin IX alpha.

“…The enzymic reaction has been studied in several laboratories for the past 17 years, and the main biocatabolic pathway has been elucidated (1)(2)(3). The first step is assumed to be hydroxylation at the meso position to form an a-oxy derivative (4), which is further converted to biliverdin IXa by two molecules of oxygen (2,(5)(6)(7). The chemical mechanisms of oxyheme cleavage by molecular oxygen, however, are still undetermined, particularly with respect to the electronic and oxidation states of the intermediates.…”