Heme Metabohsm

High levels of lead can affect heme metabohsm by combining with SH groups in enzymes such as fer-rochelatase and ALA dehydratase. This affects porphyrin metabolism. Elevated levels of protoporphyrin are found in red blood cells, and elevated levels of ALA and of coproporphyrin are found in urine. 

Cytochromes P450 (P450) form a large family of heme enzymes that catalyze a diversity of transformations including epoxidation, hydroxylation and heteroatom oxidation. The enzymes are involved in the metabohsm of many... 

Iron deficiency is the most common nutritional cause of anemia in humans. It can result from inadequate iron intake, malabsorption, blood loss, or an increased requirement, as with pregnancy. When severe, it results in a characteristic microcytic, hypochromic anemia. Iron is an essential component of myoglobin heme enzymes such as the cytochromes, catalase, and peroxidase and the metalloflavoprotein enzymes, including xanthine oxidase and the mitochondrial enzyme a-glycerophosphate oxidase. Iron deficiency can affect metabohsm in muscle independent of the effect of anemia on delivery, possibly due to a reduction in the activity of iron-dependent mitochondrial enzymes. Iron deficiency also has been associated with behavioral and learning problems in children, abnormahties in catecholamine metabolism, and impaired heat production. 

Quasi-irreversible inhibition is observed when CYP metabohsm produces an intermediate that can form a stable metabolite-intermediate MI) complex. This is another example of mechanism-based inhibition. Erythromycin is one such quasi-irreversible CYP3A4 inhibitor. Upon didemethylation of its tertiary amine group and subsequent oxidation, the resulting nitroso species forms a tight complex with the Fe(II) atom of the CYP s heme unit. Unhke truly irreversible adducts, such complexes can be broken up, say by oxidation with potassium ferricyanide, but under normal physiological conditions this obviously doesn t happen. 

Baradat, M., 1. Jonanin, S. DaUeau, S. Tache, M. Gieules et al. 2011.4-Hydroxy-2(E)-nonenal metabohsm differs in Apc(4-/+) cells and in Apc(Min/+) cells It may explain colon cancer promotion by heme iron. ChanResJj i ol 24 1984—1993. 

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