Alcoholic liver disease is a major health care problem worldwide. Findings from many laboratories, including ours, have demonstrated that ethanol feeding impairs several of the many steps involved in methionine metabo...Alcoholic liver disease is a major health care problem worldwide. Findings from many laboratories, including ours, have demonstrated that ethanol feeding impairs several of the many steps involved in methionine metabolism. Ethanol consumption predominantly results in a decrease in the hepatocyte level of S-adenosylmethionine and the increases in two toxic metabolites, homocysteine and S-adenosylhomocysteine. These changes, in turn, result in serious functional consequences which include decreases in essential methylation reactions v/a inhibition of various methyltransferases. Of particular interest to our laboratory is the inhibition of three important enzymes, phosphatidylethanolamine methyltransferase, isoprenylcysteine carboxyl methyltransferase and protein L-isoaspartate methyltransferase. Decreased activity of these enzymes results in increased fat deposition, increased apoptosis and increased accumulation of damaged proteins- all of which are hallmark features of alcoholic liver injury. Of all the therapeutic modalities available, betaine has been shown to be the safest, least expensive and most effective in attenuating ethanol-induced liver injury. Betaine, by virtue of aiding in the remethylation of homocysteine, removes both toxic metabolites （homocysteine and S-adenosylhomocysteine）, restores S-adenosylmethionine level, and reverses steatosis, apoptosis and damaged proteins accumulation. In conclusion, betaine appears to be a promising therapeutic agent in relieving the methylation and other defects associated with alcoholic abuse.展开更多
Many strategies have been proposed to produce arenes from lignin as liquid fuel additives.However,the development of these methods is limited by the low yield of products,low atom utilization,and inefficient lignin de...Many strategies have been proposed to produce arenes from lignin as liquid fuel additives.However,the development of these methods is limited by the low yield of products,low atom utilization,and inefficient lignin depolymerization.Herein,we develop an energy-efficient synthetic method for the production of high-carbon-number arenes from sustainable lignin with a total yield of 23.1 wt%.Particularly,high carbon number arenes are obtained by fully utilizing the formaldehyde stabilizing additive and the methoxy group in lignin.The process begins with the reductive depolymerization of formaldehyde-stabilized lignin,followed by transmethylation between lignin monomers over Au/Nb_(2)O_(5) catalyst,and the Ru/Nb2O5-catalyzed hydrodeoxygenation.This work demonstrates the potential of value-added arenes production directly from lignin.展开更多
Numerous transmethylation reactions are required for normal plant growth and development. S-adenosylhomocysteine hydrolase （SAHH） and adenosine kinase （ADK） act coordinately to recycle the by-product of these reac...Numerous transmethylation reactions are required for normal plant growth and development. S-adenosylhomocysteine hydrolase （SAHH） and adenosine kinase （ADK） act coordinately to recycle the by-product of these reactions, S-adenosylhomocysteine （SAH） that would otherwise competitively inhibit methyltransferase （MT） activities. Here, we report on investigations to understand how the SAH produced in the nucleus is metabolized by SAHH and ADK. Localization analyses using green fluorescent fusion proteins demonstrated that both enzymes are capable of localizing to the cytoplasm and the nucleus, although no obvious nuclear localization signal was found in their sequences. Deletion analysis revealed that a 41-amino-acid segment of SAHH （GlylS^-Lys19~） is required for nuclear targeting of this enzyme. This segment is surface exposed, shows unique sequence conservation patterns in plant SAHHs, and possesses additional features of protein-protein interaction motifs. ADK and SAHH interact in Arabidopsb via this segment and also interact with an mRNA cap MT. We propose that the targeting of this complex is directed by the nuclear localization signal of the MT; other MTs may similarly target SAHH/ADK to other subcellular compartments to ensure uninterrupted transmethylation.展开更多
基金Supported by the VA Merit Review from the Department of Veterans Affairs
文摘Alcoholic liver disease is a major health care problem worldwide. Findings from many laboratories, including ours, have demonstrated that ethanol feeding impairs several of the many steps involved in methionine metabolism. Ethanol consumption predominantly results in a decrease in the hepatocyte level of S-adenosylmethionine and the increases in two toxic metabolites, homocysteine and S-adenosylhomocysteine. These changes, in turn, result in serious functional consequences which include decreases in essential methylation reactions v/a inhibition of various methyltransferases. Of particular interest to our laboratory is the inhibition of three important enzymes, phosphatidylethanolamine methyltransferase, isoprenylcysteine carboxyl methyltransferase and protein L-isoaspartate methyltransferase. Decreased activity of these enzymes results in increased fat deposition, increased apoptosis and increased accumulation of damaged proteins- all of which are hallmark features of alcoholic liver injury. Of all the therapeutic modalities available, betaine has been shown to be the safest, least expensive and most effective in attenuating ethanol-induced liver injury. Betaine, by virtue of aiding in the remethylation of homocysteine, removes both toxic metabolites （homocysteine and S-adenosylhomocysteine）, restores S-adenosylmethionine level, and reverses steatosis, apoptosis and damaged proteins accumulation. In conclusion, betaine appears to be a promising therapeutic agent in relieving the methylation and other defects associated with alcoholic abuse.
文摘Many strategies have been proposed to produce arenes from lignin as liquid fuel additives.However,the development of these methods is limited by the low yield of products,low atom utilization,and inefficient lignin depolymerization.Herein,we develop an energy-efficient synthetic method for the production of high-carbon-number arenes from sustainable lignin with a total yield of 23.1 wt%.Particularly,high carbon number arenes are obtained by fully utilizing the formaldehyde stabilizing additive and the methoxy group in lignin.The process begins with the reductive depolymerization of formaldehyde-stabilized lignin,followed by transmethylation between lignin monomers over Au/Nb_(2)O_(5) catalyst,and the Ru/Nb2O5-catalyzed hydrodeoxygenation.This work demonstrates the potential of value-added arenes production directly from lignin.
文摘Numerous transmethylation reactions are required for normal plant growth and development. S-adenosylhomocysteine hydrolase （SAHH） and adenosine kinase （ADK） act coordinately to recycle the by-product of these reactions, S-adenosylhomocysteine （SAH） that would otherwise competitively inhibit methyltransferase （MT） activities. Here, we report on investigations to understand how the SAH produced in the nucleus is metabolized by SAHH and ADK. Localization analyses using green fluorescent fusion proteins demonstrated that both enzymes are capable of localizing to the cytoplasm and the nucleus, although no obvious nuclear localization signal was found in their sequences. Deletion analysis revealed that a 41-amino-acid segment of SAHH （GlylS^-Lys19~） is required for nuclear targeting of this enzyme. This segment is surface exposed, shows unique sequence conservation patterns in plant SAHHs, and possesses additional features of protein-protein interaction motifs. ADK and SAHH interact in Arabidopsb via this segment and also interact with an mRNA cap MT. We propose that the targeting of this complex is directed by the nuclear localization signal of the MT; other MTs may similarly target SAHH/ADK to other subcellular compartments to ensure uninterrupted transmethylation.
