Animal metabolism oxidative processes

In animal metabolism, oxomolybdoenzymes catalyse a number of oxidation processes. These oxidases contain Mo coordinated to terminal O and S atoms, and their action appears to involve loss of an O or S atom along with reduction to Mo or Mo". It is, however, the role of molybdenum in nitrogen fixation which has received most attention. 

Metals are extremely important not only for chemical reactions but also for the health and welfare of plants and animals. Some examples of metals required for good nutrition, even in trace amounts, are iron, copper, cobalt, potassium, sodium, and zinc. Other metals—for example, mercury, lead, cadmium, barium, beryllium, radium, and uranium—are very toxic. Some metals at the atomic and ionic levels are crucial for the oxidation process that metabolizes carbohydrates for all living cells. 

There is evidence that quinone methides form as intermediates in the metabolic oxidation of catechol derivatives, a key step in a variety of biosynthetic processes such as melanization and sclerotization of animal cells. Tyrosinase from mushrooms catalyzes the oxidation of a-methyldopa methyl ester 54a. It has been proposed that this reaction observed in vitro is part of a metabolic pathway for the metabolism of 54a. This reaction proceeds by oxidation of ct-methyl dopa methyl ester 54a to give 54b, which cyclizes and is further oxidized to quinone methide 54c (Scheme 26).101 This quinone methide was identified by comparison to authentic 54c, which was prepared by chemical oxidation of 54a to 54c.102... 

Heroin is rapidly hydrolyzed in vivo to 6-monoacetylmorphine (257) and thence to morphine (1) (see also p. 26). N-Demethylation and O-demethyla-tion are significant metabolic routes in animals, with the former oxidative process leading to normorphine (258) from 1, and norcodeine (259) from 2, which may in turn be eliminated as their 3- and 6-glucuronides, respectively. 

Copper and Zinc in Aerobic Metabolism. Cytochrome oxidase, the terminal oxidase in the electron transport chain contains an atom of copper. On this enzyme the protons and electrons generated during oxidative metabolism combine with elemental oxygen to form water. During copper deficiency the tissue concentration of cytochrome oxidase is reduced. While the effects of lower cytochrome oxidase activity on exercise has not been described, it is likely that aerobic energy metabolism will be diminished. This effect of copper deficiency was first described in animals with myelin aplasls — the degeneration myelin (86). The oxidative process of phospholipid synthesis, a primary component of myelin, was depressed. Liver mitochondria had impaired respiratory activity (87). Cytochrome oxidase activity was also depressed in brain, heart and liver. 

The most important metabolic processes in warm-blooded animals are oxidation of the thiol group, O-dealkylation, and reduction and hydrolysis of the nitro group. Accordingly, the most important metabolites are paraoxon (15), deethyl paraoxon... 

Oxidative processes are well-known in animal metabolism and they include pocesses that abstract hydrogen atoms from the substrate as well as those that add oxygen atoms to the substrate. For alkaloid molecules, though, oxygenation is more usual than dehydrogenation. This may be because the dehydrogenase enzymes are closely matched with the structures of their usual substrates, while oxygenases are less specific. 

FIGURE 21.18 A portion of an animal cell, showing the sites of various aspects of fatty-acid metabolism. The cytosol is the site of fatty-acid anabolism. It is also the site of formation of acyl-CoA, which is transported to the mitochondrion for catabolism by the P-oxidation process. Some chainlengthening reactions (beyond Cjg) take place in the mitochondria. Other chain-lengthening reactions take place in the endoplasmic reticulum (ER), as do reactions that introduce double bonds. 

In man, the metabolic pathways of mepirizole were distinct from those in experimental animals, since hydroxylation on each of the aromatic rings did not occur in man. Compound (752) was obtained by oxidation of the 3-methyl group to the carboxylic acid (a similar process occurs with 5-methylpyrazole-3-carboxylic acid, an active metabolite of 3,5-dimethylpyrazole). However, the carboxylic acid metabolite of mepirizole had no analgesic activity and did not decrease blood glucose. 

Mechanistic studies have shown that TBT and certain other forms of trialkyltin have two distinct modes of toxic action in vertebrates. On the one hand they act as inhibitors of oxidative phosphorylation in mitochondria (Aldridge and Street 1964). Inhibition is associated with repression of ATP synthesis, disturbance of ion transport across the mitochondrial membrane, and swelling of the membrane. Oxidative phosphorylation is a vital process in animals and plants, and so trialkyltin compounds act as wide-ranging biocides. Another mode of action involves the inhibition of forms of cytochrome P450, which was referred to earlier in connection with metabolism. This has been demonstrated in mammals, aquatic invertebrates and fish (Morcillo et al. 2004, Oberdorster 2002). TBTO has been shown to inhibit P450 activity in cells from various tissues of mammals, including liver, kidney, and small intestine mucosa, both in vivo and in vitro (Rosenberg and Drummond 1983, Environmental Health Criteria 116). 

---