清华大学生物化学,三羧酸循环技术分析.pptx

Chapter 16 The Citric Acid Cycle The common pathway leading to the complete oxidation of carbohydrates, fatty acids, and amino acids to CO2 A pathway providing many precursors for biosynthetic reactions Fates of pyruvate Citric Acid Cycle (三羧酸循环) Also called the tricarboxylic acid cycle (TCA) or the Krebs cycle Pyruvate completely oxidized to CO2 and H2O in the presence of O2---cellular respiration Occurs in eight steps in mitochondria Energy efficiently conserved A hub in metabolism, serving in both catabolic and anabolic processes 1. The cellular respiration (complete oxidation of fuels) can be divided into three stages Stage I All the fuel molecules are oxidized to generate a common two-carbon unit, acetyl-CoA. Stage II Acetyl-CoA is completely oxidized to CO2, with electrons collected by NAD and FAD via the citric acid cycle. Stage III Electrons of NADH and FADH2 are transferred to O2 via a series of carriers, producing H2O and a H+ gradient, which will promote ATP formation. 2. Pyruvate is oxidized to acetyl-CoA by the pyruvate dehydrogenase complex Pyruvate is first transported into mitochondria via a specific transporter on the inner membrane. Pyruvate is converted to acetyl-CoA and CO2 by oxidative decarboxylation. The pyruvate dehydrogenase (PDH) complex is a huge multimeric assembly of three kinds of enzymes, having 60 subunits in bacteria and more in mammals. Production of acetyl-CoA Oxidative decarboxylation Critical to its role as an acyl carrier in a number of metabolic reactions (thioester) Lipoate can act as a carrier of both hydrogen and an acetyl group Production of acetyl-CoA Oxidative decarboxylation Thiamine pyrophosphate (TPP, 硫胺焦磷酸, derived from vitamin B1) acts as the coenzyme of the decarboxylase. Pyruvate Dehydrogenase Complex (PDH) Three-enzyme complex E1: pyruvate dehydrogenase (TPP) E2: dihydrolipoyl transacetylase (lipoate)--core E3: dihydrolipoyl dehydrogenase (FAD) Plus 2 regulatory prot