Protoporphyrin iron, formation

Fig. 5.1 The structure of iron protoporphyrin IX, the prosthetic heme group of the peroxidases except where it is modified by the formation of covalent bonds to the methyl or vinyl groups. The a, (3-, y-, and 5-meso-carbon atoms, defined with respect to the pattern of the ring substituents, are labeled...

Catalase itself has been shown by Agner and Theorell (19) to have a hydroxyl group attached to the iron protoporphyrin group with a pK of 3.8. The evidence for this rests on changes in light absorption on addition of different anions such as phosphate, acetate, and formate and the inhibition of catalase activity by these anions increasing as the hydroxyl ion concentration is decreased. 

Recent discovery of nitric oxide ( NO), which controls and influences a number of critical physiological processes, as a mammalian metabolic intermediate has stimulated rapid progress of studies on nitric oxide synthase (NOS) [267-269]. The formation of NO from L-arginine in mammalian cells is catalyzed by NOS. The inducible NOS has now been known to contain a cytochrome P-450 type iron-protoporphyrin IX prosthetic group and 1 equiv each of FAD and FMN per subunit [270, 271]. Further, NOS requires NADPH to proceed the reactions. Interestingly, P-450 itself has been demonstrated to catalyze NO synthesis [272, 273]. While the detail of the reaction mechanism is still obscure. Scheme 17 summarizes proposed reaction sequences [269]. 

Formation of Heme Involves Incorporation of Iron Into Protoporphyrin... 

Figure 9-8. Pathway for metabolism of heme and excretion as bilirubin. Heme degradation begins with heme oxygenase, which catalyzes a complex set of reactions that simultaneously open the protoporphyrin ring structure and release iron in the ferric (Fe ) state. This is the only physiologic reaction that makes endogenous CO in the body a portion of the small amounts made is expired via the lungs. The structure of the main form of bilirubin is shown. Symbols for the side groups indicate M, methyl V, vinyl P, propyl. Formation of the diglucuronide is catalyzed by bilirubin uridine diphosphate (UDP) glucuronyltransferase. RE, reticuloendothelial.

Killday etal. (1988) also provided evidence for internal autoreduction of ferric nitrosyl heme complexes, as previously proposed by Giddings (1977). Heating of chlorohemin( iron-III) dimethyl ester in dimethyl sulfoxide solution with imidazole and NO produced a product with an infrared spectra identical to that of nitrosyl iron(ll) protoporphyrin dimethyl ester prepared by dithionite reduction. Both spectra clearly showed the characteristic nitrosyl stretch at 1663 and 1665 cm. They thus proposed a mechanism for formation of cured meat pigment which includes internal autoreduction of NOMMb via globin imidazole residues. A second mole of nitrite is proposed to bind to the heat-denatured protein, possibly at a charged histidine residue generated in the previous autoreduction step. 

In the early 1970s it was discovered that P-450 cytochromes are irreversibly inhibited during the metabolism of xenobiotics (1). The formation of a modified heme prosthetic group is associated with enzyme inhibition and subsequent studies have identified these modified complexes as N-alkylated protoporphyrin-IX (2). The chemistry of N-sub-stituted porphyrins was comprehensively reviewed by Lavallee in 1987 (3). Since that time, there have been many significant contributions to this field by several groups. The goal of this chapter is to summarize some of this work as it relates to the mechanism of formation and reactivity of iron N-alkyl porphyrins. Biomimetic model complexes have played an important role in elucidating the chemistry of N-alkyl hemes in much the same way that synthetic iron tetraarylporphyrins have aided... 

Biological systems overcome the inherent unreactive character of 02 by means of metalloproteins (enzymes) that activate dioxygen for selective reaction with organic substrates. For example, the cytochrome P-450 proteins (thiolated protoporphyrin IX catalytic centers) facihtate the epoxidation of alkenes, the demethylation of Al-methylamines (via formation of formaldehyde), the oxidative cleavage of a-diols to aldehydes and ketones, and the monooxygenation of aliphatic and aromatic hydrocarbons (RH) (equation 104). The methane monooxygenase proteins (MMO, dinuclear nonheme iron centers) catalyze similar oxygenation of saturated hydrocarbons (equation 105). ... 

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