S-adenosyl-L-methionine (SAM) acts as a methyl donor for methylation reactions and participates in the synthesis of glutathione. SAM is also a key metabolite that regulates hepatocyte growth, differentiation and death...S-adenosyl-L-methionine (SAM) acts as a methyl donor for methylation reactions and participates in the synthesis of glutathione. SAM is also a key metabolite that regulates hepatocyte growth, differentiation and death. Hepatic SAM levels are decreased in animal models of alcohol liver injury and in patients with alcohol liver disease or viral cirrhosis. This review describes the protection by SAM against alcohol and cytochrome P450 2E1-dependent cytotoxicity both in vitro and in vivo and evaluates mechanisms for this protection.展开更多
S-Adenosyl-L-methionine(SAM) is a cofactor serving as a methyl donor in numerous enzymatic reactions. It has been reported that SAM has the potential to modify antioxidant-enzymes, glutathione-biosynthesis and methion...S-Adenosyl-L-methionine(SAM) is a cofactor serving as a methyl donor in numerous enzymatic reactions. It has been reported that SAM has the potential to modify antioxidant-enzymes, glutathione-biosynthesis and methionine adenosyltransferases-1/2 in hepatitis C virus-expressing cells at millimolar concentrations. The efficacy of SAM at micromolar concentrations and the underlying mechanisms remain to be demonstrated.展开更多
Chemically modified cellular co-factors that provide function,such as immobilization or incorporation of fluorescent dyes,are valuable probes of biological activity.A convenient route to obtain S-adenosyl methionine（...Chemically modified cellular co-factors that provide function,such as immobilization or incorporation of fluorescent dyes,are valuable probes of biological activity.A convenient route to obtain S-adenosyl methionine（AdoMet） analogues modified at N-6 adenosine to feature a linker terminating in azide functionality is described herein.Subsequent decoration of such AdoMet analogues with guanidinium terminated linkers leads to novel potential bisubstrate inhibitors for protein arginine methyltrans-ferases, PRMTs.展开更多
基金Supported by NIH/NIAAA Grants No. AA017425Supported by NIH/NIAAA Grants No. AA018790
文摘S-adenosyl-L-methionine (SAM) acts as a methyl donor for methylation reactions and participates in the synthesis of glutathione. SAM is also a key metabolite that regulates hepatocyte growth, differentiation and death. Hepatic SAM levels are decreased in animal models of alcohol liver injury and in patients with alcohol liver disease or viral cirrhosis. This review describes the protection by SAM against alcohol and cytochrome P450 2E1-dependent cytotoxicity both in vitro and in vivo and evaluates mechanisms for this protection.
文摘S-Adenosyl-L-methionine(SAM) is a cofactor serving as a methyl donor in numerous enzymatic reactions. It has been reported that SAM has the potential to modify antioxidant-enzymes, glutathione-biosynthesis and methionine adenosyltransferases-1/2 in hepatitis C virus-expressing cells at millimolar concentrations. The efficacy of SAM at micromolar concentrations and the underlying mechanisms remain to be demonstrated.
基金financially supported by the Medical Research Council Grant(No.G0700840)
文摘Chemically modified cellular co-factors that provide function,such as immobilization or incorporation of fluorescent dyes,are valuable probes of biological activity.A convenient route to obtain S-adenosyl methionine（AdoMet） analogues modified at N-6 adenosine to feature a linker terminating in azide functionality is described herein.Subsequent decoration of such AdoMet analogues with guanidinium terminated linkers leads to novel potential bisubstrate inhibitors for protein arginine methyltrans-ferases, PRMTs.
