Porphyrin and heme metabolism

This four-volume set has good chapters on disorders of amino acid, porphyrin, and heme metabolism. See also the chapters on inborn errors of purine and pyrimidine metabolism. 

See also Chlorophyll a. Chlorophyll b, Light-Harvesting Complexes, Reaction Center, Chloroplast Anatomy, Phytanic Acid, Porphyrin and Heme Metabolism... 

See also Serum Albumin, Porphyrin and Heme Metabolism... 

See also Light Gathering Structures, Energy of Light, The Chloroplast, Photosystem II, Photosystem I, Thylakoid Membranes, Porphyrin and Heme Metabolism (from Chapter 21)... 

Bonkowsky, H.L., 1982. Porphyrin and heme metabolism and the pmphyrias. In Zakim, D., Boyer, T.D. (Eds.), Hepatology A Textbook of Liver Disease. Saunders, Hiiladelphia, PA,... 

Woods JS (1988b) Regulation of porphyrin and heme metabolism in the kidney. Semin Hematol 25 336-348... 

All mammalian cells are virtually capable of producing CO with heme as the main substrate (Fig. 1) [5]. Enzymatic heme metabolism in vivo is mainly catalyzed by heme oxygenase (HO). In the presence of HO, the porphyrin ring of heme is broken and oxidized at the a-methene bridge, producing equimolar amounts of CO, ferrous iron, and biliverdin. Three isoforms of HO have been identified. Inducible HO-1 (32 kDa) is mostly recognized for its upregulation in response... 

The simple porphyrin category includes macrocycles that are accessible synthetically in one or few steps and are often available commercially. In such metallopor-phyrins, one or both axial coordinahon sites of the metal are occupied by ligands whose identity is often unknown and cannot be controlled, which complicates mechanistic interpretation of the electrocatalytic results. Metal complexes of simple porphyrins and porphyrinoids (phthalocyanines, corroles, etc.) have been studied extensively as electrocatalysts for the ORR since the inihal report by Jasinsky on catalysis of O2 reduction in 25% KOH by Co phthalocyanine [Jasinsky, 1964]. Complexes of all hrst-row transition metals and many from the second and third rows have been examined for ORR catalysis. Of aU simple metalloporphyrins, Ir(OEP) (OEP = octaethylporphyrin Fig. 18.9) appears to be the best catalyst, but it has been little studied and its catalytic behavior appears to be quite distinct from that other metaUoporphyrins [CoUman et al., 1994]. Among the first-row transition metals, Fe and Co porphyrins appear to be most active, followed by Mn [Deronzier and Moutet, 2003] and Cr. Because of the importance of hemes in aerobic metabolism, the mechanism of ORR catalysis by Fe porphyrins is probably understood best among all metalloporphyrin catalysts. 

Within the past few years, there has been considerable progress in understanding the role played by the mitochondria in the cellular homeostasis of iron. Thus, erythroid cells devoid of mitochondria do not accumulate iron (7, 8), and inhibitors of the mitochondrial respiratory chain completely inhibit iron uptake (8) and heme biosynthesis (9) by reticulocytes. Furthermore, the enzyme ferrochelatase (protoheme ferro-lyase, EC 4.99.1.1) which catalyzes the insertion of Fe(II) into porphyrins, appears to be mainly a mitochondrial enzyme (10,11,12,13, 14) confined to the inner membrane (15, 16, 17). Finally, the importance of mitochondria in the intracellular metabolism of iron is also evident from the fact that in disorders with deranged heme biosynthesis, the mitochondria are heavily loaded with iron (see Mitochondrial Iron Pool, below). It would therefore be expected that mitochondria, of all mammalian cells, should be able to accumulate iron from the cytosol. From the permeability characteristics of the mitochondrial inner membrane (18) a specialized transport system analogous to that of the other multivalent cations (for review, see Ref. 19) may be expected. The relatively slow development of this field of study, however, mainly reflects the difficulties in studying the chemistry of iron. 

Metals may impair the metabolism of porphyrins and other heme precursors by direct or indirect compromise of heme pathway enzymes or by reducing the availability of substrates and/or cofactors required for enzyme function. 

Much remains to be accomplished with respect to the characterization and validation of porphyrins and other heme pathway parameters as biomarkers of metal exposures and effects in human subjects. Continued advances in the development of porphyrin assessment techniques and in the understanding of the mechanistic relationship of metal-induced porphyrinurias to the biological effects of metal exposures stimulate considerable interest and research in this area. Additional aspects of metal effects on heme and porphyrin metabolism have been described in previous reviews (Maines 1984 Marks 1985 Woods 1988b, 1989). 

The biosynthetic chain of chlorophyll begins with the small building blocks, acetate and glycine molecules, which are part of the basic metabolic milieu. These small molecules are condensed in a series of n steps to form the complex molecule protoporphyrin. From protoporphyrin two classes of compounds are formed namely, the iron porphyrins or hemes and the magnesium porphyrins which give rise eventually to chlorophyll. According to this scheme, heme and chlorophyll are related to each other biochemically, since both arise from the same precursor molecule, protoporphyrin. 

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