tailieunhanh - Báo cáo y học: "The 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductases"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học quốc tế cung cấp cho các bạn kiến thức về ngành y đề tài: The 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductases. | Protein family review The 3-hydroxy-3-methylglutaryl coenzyme-A HMG-CoA reductases Jon A Friesen and Victor W Rodweir Addresses Department of Chemistry Illinois State University Normal IL 61790-4160 USA. Department of Biochemistry Purdue University 175 South University Street West Lafayette IN 47907-2063 USA. Correspondence Jon A Friesen. E-mail jfriese@ Published I November 2004 Genome Biology 2004 5 248 The electronic version of this article is the complete one and can be found online at http 2004 5 11 248 2004 BioMed Central Ltd Summary The enzyme 3-hydroxy-3-methylglutaryl coenzyme A HMG-CoA reductase catalyzes the conversion of HMG-CoA to mevalonate a four-electron oxidoreduction that is the rate-limiting step in the synthesis of cholesterol and other isoprenoids. The enzyme is found in eukaryotes and prokaryotes and phylogenetic analysis has revealed two classes of HMG-CoA reductase the Class I enzymes of eukaryotes and some archaea and the Class II enzymes of eubacteria and certain other archaea. Three-dimensional structures of the catalytic domain of HMG-CoA reductases from humans and from the bacterium Pseudomonas mevalonii in conjunction with site-directed mutagenesis studies have revealed details of the mechanism of catalysis. The reaction catalyzed by human HMG-CoA reductase is a target for anti-hypercholesterolemic drugs statins which are intended to lower cholesterol levels in serum. Eukaryotic forms of the enzyme are anchored to the endoplasmic reticulum whereas the prokaryotic enzymes are soluble. Probably because of its critical role in cellular cholesterol homeostasis mammalian HMG-CoA reductase is extensively regulated at the transcriptional translational and post-translational levels. Gene organization and evolutionary history The human hmgr gene that encodes the single human HMG-CoA reductase is located on chromosome 5 map location and is over kilobases kb long. The 20 exons of the 4 475-nucleotide .