S-adenosylhomocysteine hydrolase, S-adenosylmethionine, S-adenosylhomocysteine: correlations with ribavirin induced anemia.
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| Abstract |
Objective is to speculate on the ribavirin induced anemia by inhibiting S-adenosylhomocysteine (SAH)-hydrolase activity. The major toxicity associated with the use of ribavirin is hemolytic anemia. This adverse effect has been ascribed to the accumulation of ribavirin triphosphate in the erythrocyte, which interferes with erythrocyte function. Ribavirin has been found to inhibit SAH-hydrolase activity in erythrocyte. SAH is further hydrolyzed to adenosine and homocysteine by SAH-hydrolase. The formation of S-adenosylmethionine (SAM) is then demethylated to SAH. SAH, the metabolite of SAM, on the other hand is a powerful inhibitor of methyltransferase enzymes, competing for the SAM binding site. A concurrent decrease in SAM and an increase in SAH levels would inhibit methylation of many tissue components including proteins, DNA, RNA, phospholipids and other small molecules. The enzyme protein carboxyl methyltransferase type II has been recently shown to play a crucial role in the repair of damaged proteins. SAM is the methyl donor of the reaction, and its demethylated product, SAH is the natural inhibitor of this reaction, as well as of most SAM-dependent methylations. The biological function of this transmethylation reaction is related to the repair or degradation of age-damaged proteins. Methyl ester formation in erythrocyte membrane proteins has been used as a marker reaction to tag these abnormal residues and to monitor their increase associated with erythrocyte ageing diseases. Liver disease is complicated by cholesterol deposition in hepatic and extrahepatic membranes. Erythrocyte membrane fluidity has been improved with the administration of SAM and correlated with the cholesterol/phospholipid ratio of the membranes. The levels of SAH-hydrolase activity were also found to undergo a sharp decrease with red cell ageing. The similarity of these alterations with certain morphofunctional characteristics of erythrocyte in some conditions as chronic renal failure, liver disease and hereditary spherocytosis makes it possible to hypothesize that the inhibition of SAH-hydrolase could constitute at least a part of ribavirin induced hemolytic anemia.
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| Authors | Engin Altintas, Orhan Sezgin |
| Journal | Medical hypotheses (Med Hypotheses) Vol. 63 Issue 5 Pg. 834-7 ( 2004) ISSN: 0306-9877 [Print] United States |
| PMID | 15488656 (Publication Type: Journal Article) |
| Chemical References |
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