In heme catabolism C2 and C4 vinyl groups reduction of cobalt protoporphyrin forms cobalt mesoporphyrin and alters the nature of action of the metalloporphyrin in vivo.
Heme is a tetrapyrrolic ring with iron as the central metal atom and acts as a prosthetic group for a number of enzymes, e.g. cytochromes and globins. It also plays an important role in the regulation of transcription, translation, protein translocation and erythroid differentiation. Thus, heme regulation is under strict control in the body. Our studies on the regulatory enzymes of heme anabolism, aminolevulinic acid synthetase (ALA-S), and of catabolism, heme oxygenase (HMOX), in the spleen has revealed that cobalt protoporphyrin acts as an inducer of HMOX. It is revealed that by alteration of side groups at C2 and C4 changes the nature of action of Co-protoporphyrin from an inducer to a strong inhibitor of HMOX activity. All the three analogues Co-protoporphyrin, Co-mesoporphyrin and Co-hematoporphyrin have been shown to induce the ALA-S activity to the similar extent. NADPH-cytochrome c reductase, a microsomal membrane bound enzyme, is required by HMOX for the enzymatic conversion of heme into biliverdin IXc and is also required for NADPH-dependent lipid peroxidation in the microsomes. It has been observed that Co-mesoporphyrin causes an inhibition of HMOX activity and consequently leads to an induced level of microsomal NADPH-dependent lipid peroxidation.
Chandra
R
R
B.R. Ambedkar Center for Biomedical Research, University of Delhi, India.
Malhotra
R
R
Dhawan
M
M
Kumaria
N
N
D000624:5-Aminolevulinate Synthetase / Q000096:biosynthesis; D000818:Animals; D004790:Enzyme Induction; D006418:Heme / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008652:Mesoporphyrins / Q000494:pharmacology*; D008665:Metalloporphyrins / Q000494:pharmacology*; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D011524:Protoporphyrins / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000187:drug effects* / Q000201:enzymology
D008652:Mesoporphyrins; D008665:Metalloporphyrins; D011524:Protoporphyrins; C104863:cobalt hematoporphyrin; C084061:cobalt mesoporphyrin; D006418:Heme; C007095:cobaltiprotoporphyrin; D006419:Heme Oxygenase (Decyclizing); D009251:NADPH-Ferrihemoprotein Reductase; D000624:5-Aminolevulinate Synthetase