5-Adenosyl-L-homocysteine hydrolase

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

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). 

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. 

S-Adenosyl-L-methionine is the important methyl donor in biological transmethylation to form S-adenosyl-L-homocysteine, which is hydrolyzed to adenosine and homocysteine by S-adenosyl-L-homocysteine hydrolase (E.C. 3.3.1.1) in vivo. However, equilibrium of the S-adenosyl-L-homocysteine hydrolase reaction favors the direction toward synthesis of S-adenosyl-L-homocysteine. Shimizu et al. developed a simple and efficient method for the high yield preparation of S-adenosyl-L-homocysteine with S-adenosyl-L-homocysteine hydrolase of Alcaligenes faecalis, in which the cellular content of S-adenosyl-L-homocysteine hydrolase was about 2.5% of the total soluble protein. S-Adenosyl-r-homocysteine was produced at a concentration of about 80 g I. 1 with a yield of nearly 100% 661. However, when racemic... 

Figure 17-7. Structures of adenosine and related nucleosides which serve as substrates for S-adenosyl-L-homocysteine hydrolase. 1, Adenosine 2, formycin A 3, neburalin 4, adenosine Af-oxide 5, 2-chloroadenosine 6, tubercidine 7, N6-methyladenosine 8, inosine 9, 1-methyladenosine.

The antiviral activity of (5)-DHPA in vivo was assessed in mice inoculated intranasally with vesicular stomatitis virus ( 5)-DHPA significandy increased survival from the infection. (3)-DHPA did not significandy 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 X-adenosyl-L-homocysteine hydrolase (61). Inhibition of SAH hydrolase results in the accumulation of SAH, which is a product inhibitor of 5-adenosyhnethionine-dependent methylation reactions. Such methylations are required for the maturation of vital mRNA, and hence inhibitors of SAH hydrolase may be expected to block virus replication by interference with viral mRNA methylation. 

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). 

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