S-Adenosylmethionine biosynthesis

Phosphatidylethanolamine synthesis begins with phosphorylation of ethanol-amine to form phosphoethanolamine (Figure 25.19). The next reaction involves transfer of a cytidylyl group from CTP to form CDP-ethanolamine and pyrophosphate. As always, PP, hydrolysis drives this reaction forward. A specific phosphoethanolamine transferase then links phosphoethanolamine to the diacylglycerol backbone. Biosynthesis of phosphatidylcholine is entirely analogous because animals synthesize it directly. All of the choline utilized in this pathway must be acquired from the diet. Yeast, certain bacteria, and animal livers, however, can convert phosphatidylethanolamine to phosphatidylcholine by methylation reactions involving S-adenosylmethionine (see Chapter 26). 

Adenosine triphosphate, coupled reactions and. 1128-1129 function of, 157, 1127-1128 reaction with glucose, 1129 structure of, 157, 1044 S-Adenosylmethionine, from methionine, 669 function of, 382-383 stereochemistry of, 315 structure of, 1045 Adipic acid, structure of, 753 ADP, sec Adenosine diphosphate Adrenaline, biosynthesis of, 382-383 molecular model of, 323 slructure of, 24... 

S-adenosylmethionine 406 biosynthesis of epoxide 349 bis(trimethylsilyl) peroxide (BTSP) 448, 450 bis(trimethylsilyl)urea 449 bis-oxepane ring 281... 

Despite our earlier failure in formate feeding experiments, [3- C]serine, [1,2- CJglycine, and [Me- C]methionine were found to enrich C-13 in neosaxitoxin effectively (7). The best incorporation was observed with methionine, indicating it is the direct precursor via S-adenosylmethionine. Glycine C-2 and serine C-3 must have been incorporated through tetrahydrofolate system as methyl donors in methionine biosynthesis. 

One of the most compelling targets in the polyamine biosynthesis pathway has been S-adenosylmethionine decarboxylase (SAM-DC). This target was chemically validated with the discovery of trypanocidal activity of MDL-73811 nearly two decades ago. Work to understand the unique kinetics for inhibition of this enzyme in T. brucei has shown that a catalytically... 

This type of alkylation also occurs in nature. For example, S-adenosylmethionine (SAM), an important biological methylation reagent, is involved in the biosynthesis of the antibiotic indolmycin and is responsible for the enantioselective C-methylation of an a-oxocarboxylic acid arising from tryptophan3. 

Yu and Wang431 considered that indole-3-acetic acid exerts its stimulating effect on expansion growth by inducing the synthesis of the enzyme catalyzing the conversion of S-adenosylmethionine into ACC, a conclusion at variance with the suggestion of Vioque and coworkers432 that indoleacetic acid oxidase and its substrate (IAA) participate in the last reaction in the ethylene biosynthesis pathway, namely, the formation of ethylene from ACC. 

Scheme 27 Hypothetical scheme for corronoid biosynthesis (SAM = S-adenosylmethionine)...

Harper DB, McRoberts WC, Kennedy JT (1996) Comparison of the Efficacies of Chloro-methane, Methionine, and S-Adenosylmethionine as Methyl Precursors in the Biosynthesis of Veratryl Alcohol and Related Compounds in Phanerochaete chrysosporium. Appl Environ Microbiol 62 3366... 

Carnitine biosynthesis utilizes the essential amino acid lysine, with terminal methyl groups donated by S-adenosylmethionine. Only lysine incorporated into proteins is a substrate for the methylation reaction. In humans, the final reaction in the biosynthetic pathway, catalyzed by a cytosolic hydroxylase, occurs in liver and kidney but not in cardiac or skeletal muscle. The carnitine requirement of these tissues is met by carnitine transported to them via the plasma... 

Histamine, serotonin and the catecholamines (dopamine, epinephrine and norepinephrine) are synthesized from the aromatic amino acids histidine, tryptophan and phenylalanine, respectively. The biosynthesis of catecholamines in adrenal medulla cells and catecholamine-secreting neurons can be simply summarized as follows [the enzyme catalysing the reaction and the key additional reagents are in square brackets] phenylalanine — tyrosine [via liver phenylalanine hydroxylase + tetrahydrobiopterin] —> i.-dopa (l.-dihydroxyphenylalanine) [via tyrosine hydroxylase + tetrahydrobiopterin] —> dopamine (dihydroxyphenylethylamine) [via dopa decarboxylase + pyridoxal phosphate] — norepinephrine (2-hydroxydopamine) [via dopamine [J-hydroxylasc + ascorbate] —> epinephrine (jV-methyl norepinephrine) [via phenylethanolamine jV-methyltransferase + S-adenosylmethionine]. 

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