ヒト胆汁酸-CoA：アミノ酸N-アシルトランスフェラーゼは、脂肪酸のグリシンへの共役に機能します

胆汁酸-CoA：アミノ酸N-アシルトランスフェラーゼ（Bacat）は、胆汁酸とタウリンへの胆汁酸と胆汁への排泄の結合を触媒します。By use of site-directed mutagenesis and sequence comparisons, we have identified Cys-235, Asp-328, and His-362 as constituting a catalytic triad in human BACAT (hBACAT) and identifying BACAT as a member of the type I acyl-CoAチオエステラーゼ遺伝子ファミリー。したがって、HBACATは脂肪アシルコアおよび/または脂肪酸をグリシンに加水分解する可能性があると仮定しました。We show here that recombinant hBACAT also can hydrolyze long- and very long-chain saturated acyl-CoAs (mainly C16:0-C26:0) and by mass spectrometry verified that hBACAT also conjugates fatty acids to glycine.組織の発現研究では、肝臓、胆嚢、および近位および遠位腸におけるバカトの強い発現が示されました。However, BACAT is also expressed in a variety of tissues unrelated to bile acid formation and transport, suggesting important functions also in the regulation of intracellular levels of very long-chain fatty acids.ヒト皮膚線維芽細胞における緑色蛍光タンパク質局在実験により、HbACAT酵素は主にサイトゾルであることが示されました。したがって、サイトゾルバカト酵素は、非共役胆汁酸と非エステル化非常に長鎖脂肪酸の蓄積により、毒性に対する保護に重要な役割を果たす可能性があります。

Bile acid-CoA:amino acid N-acyltransferase (BACAT) catalyzes the conjugation of bile acids to glycine and taurine for excretion into bile. By use of site-directed mutagenesis and sequence comparisons, we have identified Cys-235, Asp-328, and His-362 as constituting a catalytic triad in human BACAT (hBACAT) and identifying BACAT as a member of the type I acyl-CoA thioesterase gene family. We therefore hypothesized that hBACAT may also hydrolyze fatty acyl-CoAs and/or conjugate fatty acids to glycine. We show here that recombinant hBACAT also can hydrolyze long- and very long-chain saturated acyl-CoAs (mainly C16:0-C26:0) and by mass spectrometry verified that hBACAT also conjugates fatty acids to glycine. Tissue expression studies showed strong expression of BACAT in liver, gallbladder, and the proximal and distal intestine. However, BACAT is also expressed in a variety of tissues unrelated to bile acid formation and transport, suggesting important functions also in the regulation of intracellular levels of very long-chain fatty acids. Green fluorescent protein localization experiments in human skin fibroblasts showed that the hBACAT enzyme is mainly cytosolic. Therefore, the cytosolic BACAT enzyme may play important roles in protection against toxicity by accumulation of unconjugated bile acids and non-esterified very long-chain fatty acids.