5-Adenosyl-3-methionine, decarboxylation

Transfer of a phosphocholine residue to the free OH group gives rise to phosphatidylcholine (lecithin enzyme l-alkyl-2-acetyl-glycerolcholine phosphotransferase 2.7.8.16). The phosphocholine residue is derived from the precursor CDP-choline (see p. 110). Phos-phatidylethanolamine is similarly formed from CDP-ethanolamine and DAG. By contrast, phosphatidylserine is derived from phosphatidylethanolamine by an exchange of the amino alcohol. Further reactions serve to interconvert the phospholipids—e.g., phosphatidylserine can be converted into phosphatidylethanolamine by decarboxylation, and the latter can then be converted into phosphatidylcholine by methylation with S-adenosyl methionine (not shown see also p. 409). The biosynthesis of phosphatidylino-sitol starts from phosphatidate rather than DAG. 

Phosphatidylserine arises by an exchange of the ethanolamine residue of phosphatidylethanolamine for a seryl group. Decarboxylation of the serine of phosphatidylserine reforms phosphatidylethanolamine. Three successive methylation reactions convert phosphatidylethanolamine to phosphatidylcholine. 5-Adenosyl-methionine is the methyl-group donor (Chap. 15) (see Fig. 13-14). 

Putrescine is the precursor for synthesis of spermine and spermidine by reaction with decarboxylated S-adenosyl-methionine. 

Tyrosine is converted to dopa by the rate-limiting enzyme, tyrosine hydroxylase, which reqnires tetrahydro-biopterin and is inhibited by alpha-methyltyrosine. Dopa is decarboxylated to dopamine by L-aromatic amino acid decarboxylase, which reqnires pyridoxal phosphate (vitamin Bg) as a coenzyme. Carbidopa, which is used with l-dopa in the treatment of parkinsonism, inhibits this enzyme (see Figure 37). Dopamine is converted to norepinephrine by dopamine beta-hydroxylase, which requires ascorbic acid (vitamin C), and is inhibited by diethyldithiocarbamate. Norepinephrine is converted to epinephrine by phenyletha-nolamineN-melhyltransferase (PNMT), requiring S-adenosyl-methionine. The activity of PNMT is stimulated by corticosteroids. 

An early key intermediate in benzylisoquinoline biosynthesis is (57), which by decarboxylation affords (59) this in turn leads to (61) and on to alkaloids (Scheme 2). Confirmation of this pathway has come from a study using cell-free preparations of P. somniferum stems and seed capsules. It was found that this preparation catalysed the formation of (57), (59), and (61) from dopamine (54) plus 3,4-dihydroxyphenylpyruvic acid (55) without the addition of 5-adenosyl-methionine, NADPH, and pyridoxal phosphate, the reaction stopped at (57). The formation of the alkaloids reticuline, thebaine, codeine, and morphine, produced by whole plants, could not be detected with this cell-free system. The results confirm not only the intermediacy of (57) and (59) in benzylisoquinoline biosynthesis, but also the involvement of (54) and (55). 

Blue green algae (Nostoc, Anacystis) species form n-heptadecane from stearate by decarboxylation rather than by decarbonylation " and branched hydrocarbons with methyl at C-7 or C-8 were formed by group transfer from S-adenosyl methionine ... 

Methyl transfer is not the only kind of alkylation that can be effected by the sulphonium centre. The best studied example is the synthe s of the polyamines spermine and spermidine, important counter ions for nucleic acids. S-Adenosyl methionine undergoes a decarboxylation of the homocysteine side chain producing a thiopropyl amine derivative. The propyl amine residue then is transferred, first to one and then to the other amino group of putrescine yielding in turn spermine and spermidine . 

Now let us consider the simple phenols. In the case we were studying /7-hydroxybenzoic acid is decarboxylated to hydroquinone and can be glucosylated to arbutin by means of UDPG. For the formation of the methyl ethers of hydroquinone and arbutin, S -adenosyl methionine, active methionine, serves as the methyl group donor. 

All excess at C-3, C-4, none at C-2, thus excluding azetldlne as an Intermediate In the reaction between putresclne and decarboxylated 5-adenosyl-methionine). It has also been shown that putresclne reacts with the decarboxylated 5-adenosyl-methionine with inversion, i.e., a typical S 2 reaction ). 

Polyamine biosynthesis is associated with regulation of a number of metabolic functions including growth of cells in most of the living organisms. In mammals, ornithine is the precursor of aliphatic polyamines. Putrescine, formed by decarboxylation of the former by ornithine decarboxylase, is the first amine formed in polyamine biosynthesis. Putrescine gives rise to the other two polyamines, spermine and spermidine by successive addition of 3-aminopropyl residues derived from S-adenosyl-L-methionine (SAM) in the presence of different enzymes [44] (Chart 7). 

Methionine is converted into succinyl CoA in nine steps (Figure 23.28). The first step is the adenylation of methionine to form -adenosylmethionine (SAM ), a common methyl donor in the cell (p. 601). Loss of the methyl and adenosyl groups yields homocysteine, which is eventually processed to a-ketobutyrate. This ot-ketoacid is oxidatively decarboxylated by the a-ketoacid dehydrogenase complex to propionyl CoA, which is processed to succinyl CoA, as described on page 627. 

Mamont, P. S., Danzin, C., Wagner, J., Siat, M., Joder-Ohlenbusch, A. M. and Claverie, N. (1982) Accumulation of decarboxylated S-adenosyl-L-methionine in mammalian cells as a consequence of the inhibition of putrescine biosynthesis. Eur. J. Biochem. 123 499-504. 

Here we limit ourselves to an example of a 4Fe-4S center from the radical 5 -adenosyl-L-methionine (SAM) enzyme oxygen-independent coproporphyrinogen III oxidase HemN. This enzyme catalyzes the oxidative decarboxylation of coproporphyrinogen III to protoporphyrinogen IX during bacterial heme biosynthesis. The crystal structure of Escherichia coT/HemN revealed the presence of an unusually coordinated Iron-sulfur cluster and two molecules of SAM. 

Spermidine 4 was biosynthesized from putrescine 2 (NC4N), obtained by ornithine 1, and adenosyl-L-methionine (activated C3 unit). S -Adenosyl-L-methioninamine (decarboxylated 5-adenosyl-L-methionine) donates an aminopropyl group to putrescine 2 to form spermidine 4 in a reaction catalyzed by spermidine synthase. Homospermidine 3 is formed from two moles of putrescine 2 in an NAD" -dependent reaction catalyzed by HSS. Moreover, HSS catalyzes the NADI-dependent transfer of an aminobutyl group of spermidine 4 to putrescine 2 to form homospermidine 3. 

Putrescine, which is produced by decarboxylation of ornithine, and also arises from agmatine with catalysis by agmatinase, becomes the starting compound for the biosynthesis of spermidine and spermine. These reactions are catalysed by spermidine synthase and spermine synthase, respectively, involving S-adenosyl-L-methionine (for short AdoMet or SAM), and take place from bacteria to mammals (Figure 10.16). S-Adenosyl-L-methionine amide (dSAM) formed by decarboxylation of SAM provides trimethylene amine residue for this biosynthesis, which yields S-methyl-5 -thioadenosine (MTA). 

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