5-Adenosyl-L-homocysteine

DNA (cytosine-5-)-methyltransferase [EC 2.1.1.37] catalyzes the reaction of 5-adenosyl-L-methionine with DNA to produce 5-adenosyl-L-homocysteine and DNA containing a 5-methylcytosine residue. Site-specific DNA methyltransferase (cytosine-specific) [EC 2.1.1.73] catalyzes the reaction of 5-adenosyl-L-methionine with DNA containing a cytosine to produce 5-adenosyl-L-homocys-teine and DNA containing a 5-methylcytosine. 

This enzyme [EC 2.1.1.8] catalyzes the reaction of 5-adenosyl-L-methionine with histamine to produce 5-adenosyl-L-homocysteine and A -methylhistamine. 

This enzyme [EC 2.1.1.28], also known as phenylethanol-amine A -methyltransferase, catalyzes the reaction of S-adenosyl-L-methionine with phenylethanolamine to produce 5-adenosyl-L-homocysteine and A -methylphenyl-ethanolamine. The enzyme will act on a number of phe-nylethanolamines and will catalyze the conversion of noradrenalin (or norepinephrine) into adrenalin (or epinephrine). 

Kinetics of O-Methylaiion. The steady state kinetic analysis of these enzymes (41,42) was consistent with a sequential ordered reaction mechanism, in which 5-adenosyl-L-methionine and 5-adenosyl-L-homocysteine were leading reaction partners and included an abortive EQB complex. Furthermore, all the methyltransferases studied exhibited competitive patterns between 5-adenosyl-L-methionine and its product, whereas the other patterns were either noncompetitive or uncompetitive. Whereas the 6-methylating enzyme was severely inhibited by its respective flavonoid substrate at concentrations close to Km, the other enzymes were less affected. The low inhibition constants of 5-adenosyl-L-homocysteine (Table I) suggests that earlier enzymes of the pathway may regulate the rate of synthesis of the final products. 

The catalytic mechanism of Icmt is proposed to be an ordered bi-bi kinetic reaction [38,39]. In this mechanism, the methyl donor, SAM, binds to the active site first, followed by binding of the prenylcysteine substrate. Once the transfer reaction is complete, the methylated product is released followed by dissociation of 5-adenosyl-L-homocysteine (AdoHcy, SAH). Further biochemical and biophysical experiments are underway to further elucidate the mechanism of methyl donor and acceptor binding and catalysis of these unique enzymes. 

Figure 2.17 Biosynthesis of theobromine and caffeine in Coffea arabica. SAM, 5-adenosyl-L-methionine SAH, 5-adenosyl-L-homocysteine.

Stolowitz ML, Minch MJ. S-Adenosyl-L-methionine and 5 -Adenosyl-L-homocysteine, an NMR Study. J. Am. Chem. Soc. 1981 103 6015-6019. 

Fig. 7. Biosynthesis of choline plasmalogens (plasmenylcholines) via modification of the sn-3 polar head group of ethanolamine plasmalogens (plasmenylethanolamines). These reactions are proposed to be catalyzed directly by (1) a base exchange enzyme or (II) At-methyltransferase. A combination of other enzymatic reactions could also result in replacement of the ethanolamine moiety of plasmenylethanolamine to produce plasmenylcholines the enzymes responsible include (IB) phospholipase C, (IV) the reverse reaction of ethanolamine phosphotransferase, (V) phospholipase D, (VI) phosphohydtolase, and (VII) cholinephosphotransferase. AdoMet, 5-adenosyl-L-methionine AdoHcy, 5-adenosyl-L-homocysteine Etn, ethanolamine GPE, sn-glycero-...

S-methyl group to one of the two hydroxyl groups of a catechol to give a methylated catechol and 5-adenosyl-L-homocysteine, Figure 8. Catechol 0-methyltransferase is a monomeric enzyme that catalyzes the O-methylation of a variety of catecholamine neurotransmitters such as dopamine. It requires magnesium ions [42], and the rate-determining step appears to be transfer of the methyl group [43, 44],... 

Affinity chromatographic purification of 5-adenosyl-L-homocysteine hydrolase from rat liver... 

The natural form is the L-(+)-isomer. Due to the asymmetry of the sulfonium group, there are 4 stereoisomers. SAM is unstable at room temperature, both as a solid and in aqueous solution. It is synthesized in the cell by transfer of the adenosine residue of ATP to L-methionine Met + ATP -> SAM + PPi + P. When SAM donates a methyl group it is converted into 5-adenosyl-L-homocysteine, which is then cleaved to adenosine and L-homocysteine. The latter is remethylated to L-Methionine (see). [F. Takusagawa et al. Crystal Structure of S-Adenosylmethionine Synthetase J. Biol. Chem. 271 (1996) 13 147]... 

Transmethylation reactions are widely used in modification of a variety of biomolecules such as nucleic acids, proteins, phospholipids, and bioamines. In these reactions, SAM serves as the universal methyl donor (Mato et al. 1997). Methylation reactions yield the common product 5-adenosyl-L-homocysteine (SAH), and most SAM-dependent methylations are strongly inhibited by accumulation of SAH (Mato... 

Scheme 1. Mechanism proposed for 5-adenosyl-L-homocysteine hydrolase...

Sunkara, and P. Bey, 4, 5 -Unsaturated 5 -halogenated nucleosides. Mechanism-based and competitive inhibitors of 5-adenosyl-L-homocysteine hydrolase, /. Med. Chem. 34 647 (1991). 

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