5- Adenosylmethionine

Metabolic interrelations between 5-adenosylmethionine, folates, and vitamin Bl2 96CLY165. 

Divalent sulfur compounds are achiral, but trivalent sulfur compounds called sulfonium stilts (R3S+) can be chiral. Like phosphines, sulfonium salts undergo relatively slow inversion, so chiral sulfonium salts are configurationally stable and can be isolated. The best known example is the coenzyme 5-adenosylmethionine, the so-called biological methyl donor, which is involved in many metabolic pathways as a source of CH3 groups. (The S" in the name S-adenosylmethionine stands for sulfur and means that the adeno-syl group is attached to the sulfur atom of methionine.) The molecule has S stereochemistry at sulfur ana is configurationally stable for several days at room temperature. Jts R enantiomer is also known but has no biological activity. 

Methionine. Methionine reacts with ATP forming 5-adenosylmethionine, active methionine (Figure 30-17). Subsequent reactions form propionyl-CoA (Figure 30-18) and ultimately succinyl-CoA (see Figure 19-2). 

Adenosylmethionine, the principal source of methyl groups in the body, also contributes its carbon skeleton for the biosynthesis of the 3-diaminopropane portions of the polyamines spermine and spermidine (Figure 31-4). 

Adenosylmethionine, the methyl group donor for many biosynthetic processes, also participates direcdy in spermine and spermidine biosynthesis. 

When acting as a methyl donor, 5-adenosylmethionine forms homocysteine, which may be remethylated by methyltetrahydrofolate catalyzed by methionine synthase, a vitamin Bj2-dependent enzyme (Figure 45-14). The reduction of methylene-tetrahydrofolate to methyltetrahydrofolate is irreversible, and since the major source of tetrahydrofolate for tissues is methyl-tetrahydrofolate, the role of methionine synthase is vital and provides a link between the functions of folate and vitamin B,2. Impairment of methionine synthase in Bj2 deficiency results in the accumulation of methyl-tetrahydrofolate—the folate trap. There is therefore functional deficiency of folate secondary to the deficiency of vitamin B,2. 

Anton DL, R Kutny (1987) Escherichia coli 5-adenosylmethionine decarboxylase. Subunit structure, reductive amination, and NHj-terminal sequences. J Biol Chem 262 2817-2822. 

Cacciapuoti G, M Porcelli, M de Rosa, A Gambacorta, C Bertoldo, V Zappia (1991) 5 -adenosylmethionine decarboxylase from the thermophilic archaebacterium Sulfolobus solfataricus. Putification, molecular properties and studies on the covalently bound pyruvate. Eur J Biochem 199 395-400. 

Lu ZJ, GD Markham (2004) Catalytic properties of the archaeal 5-adenosylmethionine decarboxylase from Methanococcus jannaschii. J Biol Chem 279 265-273. 

Toms AV, C Kinsland, DE McCloskey, AE Pegg, SE Ealick (2004) Evolutiouary liuks as revealed hy the structure of Thermotoga maritima 5-adenosylmethionine decarboxylase. J Biol Chem 279 33837-33846. 

Tomato Agritrope/1996 5-Adenosylmethionine hydrolase Escherichia coli bacteriophage T3 Delayed fruit ripening due to reduced ethylene synthesis... 

As would be expected, the chemistry is complex. Unpleasant, off flavor odors usually derive from sulfur compounds, such as MT, DMS, DMDS, and DMTS, formed either enzymatically or non-enzymatically from sulfur-containing amino acids.35 Enzymatic routes to MT are essentially those previously considered (Section 11.1.2.4.5). Some DMS may derive by methylation of MT (Equation 8) with the donor, 5-adenosylmethionine, AdoMet ... 

The compounds that are the immediate methyl gronp donors are methyltetra hydrofate (CH3-FH4) and S-adenosyl methionine (SAM) (see Figure 15.2). These are involved in, at least, five key reactions or processes which are summarised in Figure 15.4. Complexity arises in the topic of methyl group transfer in formation and reformation of the methylating compounds 5-adenosylmethione and methyl tetrahydrofolate. There are four important reactions in the formation utilisation and then the reformation of 5-adenosylmethionine as follows ... 

This enzyme [EC 2.1.1.6] catalyzes the reaction of catechol with 5-adenosylmethionine to produce. S-adenosyl-homocysteine and guaiacol (or, o-methoxyphenol). 

The synthesis of alkaloids from L-ornithine starts with decarboxylation by the Pyridoxal Phosphate (PLP) to putrescine (Figure 33) and putrescine metylation by 5 -Adenosylmethionine (SAMe) to A-methylputrescine. The SAM is a naturally occurring reaction, when the departing groups convert... 

Adenosylmethionine (SAM) is a donor of a methyl group in numerous biological methylations. It is first transformed into 5-adenosylhomocysteine (SAH), then into adenosine and homocysteine by SAH hydrolase. 

The pyruvate carboxylase reaction requires the vitamin biotin (Fig. 16-16), which is the prosthetic group of the enzyme. Biotin plays a key role in many carboxyla-tion reactions. It is a specialized carrier of one-carbon groups in their most oxidized form C02. (The transfer of one-carbon groups in more reduced forms is mediated by other cofactors, notably tetrahydrofolate and 5-adenosylmethionine, as described in Chapter 18.)... 

After removal of their amino groups, the carbon skeletons of amino acids undergo oxidation to compounds that can enter the citric acid cycle for oxidation to C02 and H20. The reactions of these pathways require a number of cofactors, including tetrahydrofolate and 5-adenosylmethionine in one-carbon transfer reactions and tetrahydrobiopterin in the oxidation of phenylalanine by phenylalanine hydroxylase. 

FIGURE 21-27 The "salvage" pathway from phosphatidylserine to phosphatidylethanolamine and phosphatidylcholine in yeast. Phos-phatidylserine and phosphatidylethanolamine are interconverted by a reversible head-group exchange reaction. In mammals, phosphatidylserine is derived from phosphatidylethanolamine by a reversal of this reaction adoMet is 5-adenosylmethionine adoHcy, 5-adenosy I homocysteine. 

Plants and bacteria produce the reduced sulfur required for the synthesis of cysteine (and methionine, described later) from environmental sulfates the pathway is shown on the right side of Figure 22-13. Sulfate is activated in two steps to produce 3-phosphoadeno-sine 5 -phosphosulfate (PAPS), which undergoes an eight-electron reduction to sulfide. The sulfide is then used in formation of cysteine from serine in a two-step pathway. Mammals synthesize cysteine from two amino acids methionine furnishes the sulfur atom and serine furnishes the carbon skeleton. Methionine is first converted to 5-adenosylmethionine (see Fig. 18-18), which can lose its methyl group to any of a number of acceptors to form A-adenosylhomocysteine (adoHcy). This demethylated product is hydrolyzed to free homocys-... 

An analogy is found in biological systems in which 5-adenosylmethionine is a universal donor of methyl groups. 

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