Aromatic Intermediary metabolism

S-adenosyl-L-methionine (SAM)-dependent methyl-ation was briefly discussed under Thiomethylation (see Figure 14). Other functional groups that are methylated by this mechanism include aliphatic and aromatic amines, N-heterocyclics, monophenols, and polyphenols. The most important enzymes involved in these methylation reactions with xenobiotics are catechol O-methyltransferase, histamine N-methylt-ransferase, and indolethylamine N-methyltransferase - each catalyzes the transfer of a methyl group from SAM to phenolic or amine substrates (O- and N-methyltransferases, respectively). Methylation is not a quantitatively important metabolic pathway for xenobiotics, but it is an important pathway in the intermediary metabolism of both N- and O-contain-ing catechol and amine endobiotics. 

Goodwin, Brian L. Handbook of Intermediary Metabolism of Aromatic Compounds. New York Wiley, 1976 distributed in U.S. by Halsted Press. 

Goodwin, B.L. "Handbook of Intermediary Metabolism of Aromatic Compounds Chapman and Hall, London 1976. 

Despite the relatively few steps in intermediary metabolism of the aromatic amino acids, a large number of metabolic errors have been reported. Some, like phenylketonuria, lead to dramatic clinical situations, whereas others, like alkaptonuria, are less clinically important, and still others, like tyrosinosis, have no clinical significance. The reasons for many errors in a given pathway are not understood. Metabolic errors may be as common in other metabolic pathways, but they are not observed either because they do not lead to clinical alterations or because they are lethal. However, the genes concerned with the appearance of each enzyme involved in a specific metabolic pathway may be located on adjacent loci in the chromosome, and these loci are perhaps more prone to spontaneous mutation. 

Fig. 3-20. Pathology of the intermediary metabolism of the aromatic amino acids...

In the next metabolic steps the aromatic ring is cleaved and the compounds are converted via meta or ortho fission to pyruvate or succinate and acetyl-Co-A (Fig. 5.6). There are the key elements of intermediary metabolic pathways, necessary for the synthesis of cell building blocks or energy production. 

Specific aliphatic and aromatic hydrocarbons found in petroleum products are known to be metabolized via cytochrome P-450 pathways to reactive metabolic intermediates that are thought to cause non-cancer and cancer effects from chronic exposure (e.g., peripheral neuropathy from 2,5-hexadione, a metabolite of hexane, and cancer effects from various intermediary metabolites of benzene and carcinogenic PAHs). There are no known clinical methods to interfere with these mechanisms of action. However, current research programs are studying the basis of how the consumption of cruciferous vegetables may protect... 

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