Oxidative coupling pathways, enzymes

From L-tyrosine, or alternatively from L-phenylalanine, there is one further alkaloid biosynthesis pathway. This is the galanthamine pathway (Figure 38). Galanthamine synthesizes with tyramine, norbelladine, lycorine, crinine, N-demethylnarwedine and Al-demethylgalanthamine. Schiff base and reduction reaction, oxidative coupling and enzyme NADPH and SAM activity occur in this pathway. Schiff base is a reaction for the ehmination of water in formation with the C—N bonds process. 

Oxidative Reactions. The majority of pesticides, or pesticide products, are susceptible to some form of attack by oxidative enzymes. For more persistent pesticides, oxidation is frequently the primary mode of metaboHsm, although there are important exceptions, eg, DDT. For less persistent pesticides, oxidation may play a relatively minor role, or be the first reaction ia a metaboHc pathway. Oxidation generally results ia degradation of the parent molecule. However, attack by certain oxidative enzymes (phenol oxidases) can result ia the condensation or polymerization of the parent molecules this phenomenon is referred to as oxidative coupling (16). Examples of some important oxidative reactions are ether cleavage, alkyl-hydroxylation, aryl-hydroxylation, AJ-dealkylation, and sulfoxidation. 

Oxidative polymerization of phenol derivatives is also important pathway in vivo, and one example is the formation of melanin from tyrosine catalyzed by the Cu enzyme, tyrosinase. The pathway from tyrosine to melanin is described by Raper (7) and Mason (8) as Scheme 8 the oxygenation of tyrosine to 4-(3,4-dihydro-xyphenyl)-L-alanin (dopa), its subsequent oxidation to dopaqui-none, its oxidative cyclization to dopachrome and succeeding decarboxylation to 5,6-dihydroxyindole, and the oxidative coupling of the products leads to the melanin polymer. The oxidation of dopa to melanin was attempted here by using Cu as the catalyst. 

Figure 6.3 (Right) Schematic depiction of anammox cell showing the anammoxozome and nucleoid. (Left) Postulated pathway of anaerobic ammonium oxidation coupled to the ana-mmoxosome membrane resulting in a proton motive force and ATP synthesis via membrane-bound ATPases. HH, hydrazine hydrolase HZO, hydrazine oxidizing enzyme NIR, nitrite reductase. (Redrawn from van Niftrik etal., 2004 and Kuypers et al., 2006).

Numerous L-tyrosine containing peptides and proteins may be utilised to synthesise thyroxine (80) by iodination and without enzymic mediation . Iodine reacts with the L-tyrosine residues in the peptide to form mono- and di-iodo-L-tyrosine residues. An oxidative coupling of two, appropriately placed, di-iodo-L-tyrosyl residues then occurs to give thyroxine (80). Considerable evidence has been accumulated to surest that thyroxine biosynthesis follows the same pathway in vivo, but other mechanisms have been suggested and examined . The exact role of the protein thyroglobulin in thyroxine biosynthesis is, however, not clear for although L-tyrosine residues of other proteins may be readily iodinated in vitro only thyroglobulin is known to make thyroxine in vivo. 

The importance of having adequate supplies of NADPH for the regeneration of these various enzymes cannot be over emphasized. In normal situations this cofactor can be adequately provided by the reductive pentose phosphate pathway. Monitoring the activity of the pentose phosphate pathway has been proposed as a unique way to study the metabolic response to oxidative stress, since the glutathione peroxidase activity is coupled via glutathione reductase to the enzyme glucose-6-phosphate dehydrogenase (Ben Yoseph et ah, 1994). 

Another important example of catalytic oxidation of inorganic compounds by peroxidases is the catalysis of iodide oxidation by TPO. TPO is involved in the biosynthesis of thyroid hormone and catalyzes the reactions of iodination and coupling in the thyroid gland. Magnusson et al. [215] considered two possible pathways of iodination the formation of enzyme-bound hypoiodite and the formation of free hypoiodide (Reactions (17) and (18)) ... 

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