S’-adenosyl-L-homocysteine

S-adenosyl-L-homocysteine S-adenosyl-L-methionine Su(var)3-9 (suppressor of variegation 3-9), E(z) (enhancer of zeste), and trithorax domain... 

Three-dimensional X-ray crystal structures of the SET domains of >10 PMTs and the catalytic domain of DOT1L have been reported to date [25-27]. These structures, either in the apo-state or when bound to the cofactor product S-adenosyl-L-homocysteine (SAH), a histone peptide, or an inhibitor, yield key structural insights into enzyme/substrate/cofactor/inhibitor interactions and inform approaches to further inhibitor design. 

This enzyme [EC 2.1.1.72] catalyzes the reaction of S-adenosyl-L-methionine with an adenine residue in DNA to produce S-adenosyl-L-homocysteine and a 6-methyl-aminopurine residue in DNA. 

Methyltransferases that utilize S-adenosyl-L-methionine as the methyl donor (and thus generating S-adenosyl-L-homocysteine) catalyze (a) A-methylation (e.g., norepinephrine methyltransferase, histamine methyltransferase, glycine methyltransferase, and DNA-(adenine-A ) methyltransferase), (b) O-methylation (e.g., acetylsero-tonin methyltransferase, catechol methyltransferase, and tRNA-(guanosine-0 ) methyltransferase), (c) S-methyl-ation (e.g., thiopurine methyltransferase and methionine S-methyltransferase), (d) C-methylation (eg., DNA-(cy-tosine-5) methyltransferase and indolepyruvate methyltransferase), and even (e) Co(II)-methylation during the course of the reaction catalyzed by methionine syn-thase. ... 

Enzymatic O-methylation of flavonoids, which is catalyzed by O-methyltransferases (E.C. 2.1.1.6-) involves the transfer of the methyl group of an activated methyl donor, S -adenosyl-L-methionine, to the hydroxyl group of a flavonoid acceptor with the formation of the corresponding methylether and S -adenosyl-L-homocysteine. The latter product is, in... 

The reaction of [Pt(dien)Cl]Cl with S-adenosyl-L-homocysteine (SAH, a biologically relevant molecule, as it is the coproduct of the methyl transfer reaction by S-adenosyl-L-methionine see Fig. 15) results in a mixture of complexes (193), i.e., the mononuclear complex (1) [Pt(dien)(SAH-S)]2+, with platination of SAH at the sulfur atom, the mononuclear complex (2) [Pt(dien)(SAH-ADJ+, which has a Pt(dien)2+ unit coordinated to the amino group of the homocysteine unit, and the dinuclear complex (3) [ Pt(dien) 2(SAH-S,AD]3+, which has a Pt(dien)2+ unit coordinated to the sulfur atom as well as a Pt(dien)2+... 

Hanessian, S. et al. Design and Synthesis of Mimics of S-Adenosyl-L-Homocysteine as Potential Inhibitors of Erythromycin Methyltransferases. 3.1 2000 [123]... 

The 5 -alkynyl(cyano) derivatives of adenosine 274 and its carbocyclic analog derivatives 231 and 232 were examined as inhibitors of S-adenosyl-L-homocysteine and S-adenosyl-L-methionine hydrolase (89EUP334361). 

A-methylation is an important reaction by which primary, secondary, and tertiary amines are substrates of methylation. Most tissues catalyze the methylation of a large variety of amines. The source of the methyl group that is transferred in each instance is SAM, and the products are secondary, tertiary or quaternary N-methylamines as well as. S -adenosyl-L-homocysteine (SAH). The reaction shown below is with a primary amine as substrate and is catalyzed by an amine N- m e I h y I transferas e. 

The enzyme converts erythromycin C into erythromycin A in the presence of AdoMet. Evidence was obtained that the enzyme is associated with the microsomal fraction. The enzyme showed a very high degree of substrate specificity. Aside from erythromycin C, it failed to catalyze the methylation of any other L-mycarosyl moiety tested. Erythromycin A and S-adenosyl-L-homocysteine (AdoHcy) were potent inhibitors of the enzyme, and it was assumed that the Ado-Met AdoHcy ratio could be a major regulatory factor of the final step in the formation of erythromycin A. 

The reactants and products were separated on an MOS Hypersil column (4.6 millimeters x 200 mm, 5 /urn). The mobile phase was composed of a 90 10 mixture of solvent A, consisting of 0.1 M sodium acetate, 0.02 M citric acid, 0.93 mM sodium octanesulfonate, and 0.12 mM disodium EDTA (pH 4.6), and solvent B, methanol UV detection was used, with the optimal wavelength being 258 nm for the adenoxyl derivatives and 279 nm for adrenaline and noradrenaline. Quantitation was normally based on the S-adenosyl-L-homocysteine formed. 

Figure 2.16 Biosynthesis of rutacridone in Ruta graveolens. SAM, S-adenosyl-L-methionine SAH, S-adenosyl-L-homocysteine.

S-Adenosyl-L-homocysteine (10) (Fig. 17.12), the product of the reaction, and 2-(2,5-dichlorophenyDcyclopropylamine (1 l)are analogs of S-adenosyl-L-methionine and norepinephrine, respectively. Using these inhibitors it was possible to ascertain the binding order of the two substrates (75). Kinetic analyses showed that SAH was a competitive inhibitor of SAM and a noncompetitive inhibitor of norepinephrine, whereas (1 l)was a competitive inhibitor of norepinephrine and an uncompetitive inhibitor of SAM. This indicates that the binding of substrates is ordered, with SAM binding first. If norepinephrine bound first, it would be expected that SAH would be an uncompetitive inhibitor and (1 l)would be noncompetitive with respect to SAM. If a random... 

Robins, M. J., Wnuk, S. F., Mullah, K. B. and Dailey, N. K. (1994) Nucleic Acid related compounds. 80. Synthesis of 5 -5-(alkyl and aryl )-5 -(l uoro-5 -thioadenosi ncs with xenon difluoride or (diethylamido)sulfur trifluoride, hydrolysis in aqueous buffer, and inhibition of S-adenosyl-L-homocysteine hydrolase by derived adenosine 5 -aldehyde species. J. Org. Chem., 59, 544-555. 

Elevated concentrations of plasma homocysteine (HCY) are related to an increased risk of cardiovascular disease, which exists in numerous forms in plasma, with the main form existing as a disulfide with itself, cysteine, or albumin. Therefore, the first step in the measurement involves treatment with a reducing agent, in this case dithiothreitol (DTT), to obtain HCY in its free form (Eq. 16.34). Some amino acids (e.g., L-cysteine and L-methionine) are present in human plasma at higher molar concentrations than HCY and may interfere with this assay. To avoid this possible interference, the highly selective enzymatic conversion of HCY to S-adenosyl-L-homocysteine (SAH), as shown in Eq. 16.34, is used. Both reactions (reduction and conjugation) are accomplished in 30 min at 34 °C. 

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