L-Homocysteine

The antiviral activity of (5)-DHPA in vivo was assessed in mice inoculated intranasaHy with vesicular stomatitis vims ( 5)-DHPA significantly increased survival from the infection. (5)-DHPA did not significantly reduce DNA, RNA, or protein synthesis and is not a substrate for adenosine deaminase of either bacterial or mammalian origin. However, (5)-DHPA strongly inhibits deamination of adenosine and ara-A by adenosine deaminase. Its mode of action may be inhibition of Vadenosyl-L-homocysteine hydrolase (61). Inhibition of SAH hydrolase results in the accumulation of SAH, which is a product inhibitor of Vadenosylmethionine-dependent methylation reactions. Such methylations are required for the maturation of vital mRNA, and hence inhibitors of SAH hydrolase may be expected to block vims repHcation by interference with viral mRNA methylation. 

Relatively few reports have been published subsequently on the use of these reagents. Hope and coworkers99 have used sodium in liquid ammonia to cleave the benzyl sulphonyl derivatives of cysteamine, L-cysteine and L-homocysteine to prepare the corresponding sulphinic acids, as in equation (42). 

There are numerous abnormalities of cysteine metabolism. Cystine, lysine, arginine, and ornithine are excreted in cystine-lysinuria (cystinuria), a defect in renal reabsorption. Apart from cystine calculi, cystinuria is benign. The mixed disulfide of L-cysteine and L-homocysteine (Figure 30-9) excreted by cystinuric patients is more soluble than cystine and reduces formation of cystine calculi. Several metabolic defects result in vitamin Bg-responsive or -unresponsive ho-mocystinurias. Defective carrier-mediated transport of cystine results in cystinosis (cystine storage disease) with deposition of cystine crystals in tissues and early mortality from acute renal failure. Despite... 

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. 

Intramolecular replacement of sulfur by nitrogen has been reported in the complex of [Pt(dien)]2+ with S-guanosyl-L-homocysteine (sgh) according to reaction 2,... 

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. 

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 cobalamin-dependent enzyme [EC 2.1.1.13], also known as methionine synthase and tetrahydropteroyl-glutamate methyltransferase, catalyzes the reaction of 5-methyltetrahydrofolate with L-homocysteine to produce tetrahydrofolate and L-methionine. Interestingly, the bacterial enzyme is reported to require 5-adenosyl-L-methionine and FADH2. See also Tetrahydropteroyl-triglutamate Methyltransferase... 

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... 

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. 

Difluorocysteine, like 3,3-difluoroserine, is unstable. However, a protected derivative has been described. Conversely, 3,3-difluoro-L-homocysteine and 3, 3-difluoro-L-methionine are much more stable. They are prepared from difluoro-homoserine. This latter is prepared through a multistep synthesis starting from isoascorbic acid (Figure 5.24). ... 

Figure 5.24 Synthesis of difluoro-L-homocysteine and difluoro-L-methionine. ...

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