三羧酸循环柠檬酸循环.pptxVIP

第1页/共53页三羧酸循环柠檬酸循环TCA背景知识第2页/共53页1、为什么称为柠檬酸循环、三羧酸循环（Tricarboxylic acid cycle, TCA） 、Krebs循环？ 在有氧的情况下，葡萄糖酵解产生的丙酮酸氧化脱羧形成乙酰CoA。乙酰CoA经一系列氧化、脱羧，最终生成C2O和H2O并产生能量的过程，称为柠檬酸循环，亦称为三羧酸循环(tricarboxylic acid cycle), 简称TCA循环。由于它是由H.A.Krebs（德国）正式提出的，所以又称Krebs循环。第3页/共53页“It is convenient to use a brief term for the kind of scheme. Its essential feature is the periodic formation of a number of di- and tricarboxylic acids. As there is no term which would serve as a common denominator for all the various acids, it seemed reasonable to name the cycleKrebs, 1901-1981after one, or some, of its characteristic and specific acids. It was from such considerations that the term citric acid cycle was proposed in 1937.” （Hans A. Krebs, The citric acid cycle, Nobel Lecture, December 11, 1953）第4页/共53页Brief history of TCAThe first major investigation into the intermediary metabolism of oxidation was that of Thunberg, who examined systematically the oxidizability of organic substances in isolated animal tissues. Between 1906 and 1920 he tested the oxidation of over 60 organic substances, chiefly in muscle tissue. He discovered the rapid oxidation of the salts of a number of acids, such as lactate(乳酸盐), succinate(琥珀酸盐), fumarate(延胡索酸盐), malate(苹果酸盐), citrate(柠檬酸盐), and glutamate(谷氨酸盐).第5页/共53页In 1932, Krebs was studying the rates of oxidation of small organic acids by kidney and liver tissue. Only a few of substances were active in these experiments---notably succinate, fumarate, acetate, malate, and citrate.第6页/共53页An important development came from the laboratory of Szent-Gyorgyi of Szegedin 1935, who confirmed on pigeon breast muscle the rapid oxidation of the C4-dicarboxylic acids - succinic, fumaric, malic, and oxaloacetic acids - and arrived at the new conclusion that those dicarboxylic acids were linked by an enzymatic pathway that was important for aerobic metabolism. 第7页/共53页A decisive contribution to the field was made in March 1937 by Martius and Knoop, who discovered α-ketoglutarate( α-