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Alanine and aspartate aminotransferase and glutamine-cycling pathway:Their roles in pathogenesis of metabolic syndrome

查看全文 作　　者：Silvia [1]Sookoian;Carlos J [2]Pirola 高影响力作者 机构地区：[1]Department of Clinical and Molecular Hepatology,Institute of Medical Research A Lanari-IDIM,University of Buenos Aires-National Council of Scientific and Technological Research(CONICET),Ciudad Autónoma de Buenos Aires 1427,Argentina;[2]Department of Molecular Genetics and Biology of Complex Diseases,Institute of Medical Research A Lanari-IDIM,University of Buenos Aires-National Council of Scientific and Technological Research(CONICET),Ciudad Autónoma de Buenos Aires 1427,Argentina高影响力机构 出　　处：《World Journal of Gastroenterology》索引2012年第18卷第29期,共7页高影响力期刊 基　　金：Supported by Grants PICT 2008-1521 and 2010-0441,from Agencia Nacional de Promoción Científica y Tecnológica;UBACYT CM04,from Universidad de Buenos Aires 摘　　要：Although new research technologies are constantly used to look either for genes or biomarkers in the prediction of metabolic syndrome(MS),the pathogenesis and pathophysiology of this complex disease remains a major challenge.Interestingly,Cheng et al recently investigated possible pathways underlying MS by high-throughput metabolite profiling in two large and well characterized community-based cohorts.The authors explored by liquid chromatography and mass spectrometry the plasma concentrations of 45 distinct metabolites and examined their relation to cardiometabolic risk,and observed that metabolic risk factors such as obesity,insulin resistance(IR),high blood pressure,and dyslipidemia were associated with several metabolites,including branched-chain amino acids,other hydrophobic amino acids,tryptophan breakdown products,and nucleotide metabolites.In addition,the authors found a significant association of IR traits with glutamine,glutamate and the glutamineto-glutamate ratio.These data provide new insight into the pathogenesis of MS-associated phenotypes and introduce a crucial role of glutamine-cycling pathway as prominently involved in the development of metabolic risk.We consider that the hypothesis about the role of abnormal glutamate metabolism in the pathogenesis of the MS is certainly challenging and suggests the critical role of the liver in the global metabolic modulation as glutamate metabolism is linked with aminotransferase reactions.We discuss here the critical role of the 'liver metabolism' in the pathogenesis of the MS and IR,and postulate that before fatty liver develops,abnormal levels of liver enzymes,such as alanine and aspartate aminotransferases might reflect high levels of hepatic transamination of amino acids in the liver. 关 键 词：氨基转移酶 代谢综合征 发病机制 天门冬氨酸 谷氨酰胺 丙氨酸 循环 支链氨基酸
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