Lecture 20: Tricarboxylic Acid Cycle (PDF)

Lippincott’s illustrated reviews Chapter 9 – Page 109 Lecture 20 Tricarboxylic Acid Cycle (TAC) 1  Specific Objectives By the end of this lecture students can be able to: Discuss the alternate fates of pyruvate. Understand the importance of TCA...

Lippincott’s illustrated reviews Chapter 9 – Page 109 Lecture 20 Tricarboxylic Acid Cycle (TAC) 1  Specific Objectives By the end of this lecture students can be able to: Discuss the alternate fates of pyruvate. Understand the importance of TCA in the major nutrients metabolism. Know the molecules of energy released from TAC. 2 Integration of Major Metabolic Pathways by Aeropic Citric acid cycle Carbohydrates are metabolized through glycolytic pathway to pyruvate, then converted to acetyl CoA, which enters the citric acid cycle. Fatty acids through beta oxidation, are broken down to acetyl CoA and then enters this cycle. Amino acids after transamination enter into some or other points in this cycle. Citric acid cycle plays a critical role in the integration of metabolic pathways. 3 4  I if 5  ALTERNATE FATES OF PYRUVATE A. Oxidative decarboxylation of pyruvate Is an important pathway in tissues with a high oxidative capacity, such as cardiac muscle. Acetyl- CoA, is a major fuel for the TCA cycle and the building block for fatty acid synthesis. 6 B. Carboxylation of pyruvate to oxaloacetate This reaction is important because it only from carbohydrate replenishes the citric cycle (TCA cycle) intermediates, and provides substrate for gluconeogenesis. if this enzyme Actey CoA is not there there will be acanniation of pyruvate sourse will turn to Lactate then cactateacido 7  Metabolic defects of oxidative metabolism Enzyme Reaction Abnormalities catalyzed Pyruvate Pyruvate to acetyl CoA Lactic acidosis dehydrogenase Neurological disorders Pyruvate carboxylase C Pyruvate to oxaloacetate Oxaloacetate needed for sparking TCA cycle is deficient. Lactic acidosis, hyperammonemia and hyperalaninemia 8  Citric acid cycle (CAC) or Tricarboxylic Acid Cycle (TCA) or Krebs Cycle 9  Overview of TAC The tricarboxylic acid cycle (TAC) called Krebs cycle or citric acid cycle (CAC). It plays several roles in metabolism. The cycle occurs totally in the mitochondria. Anabolism and catablosion It is amphibolic pathway. 10  Fu the Et only understand 11  Influx of TCA cycle intermediates 12  Efflux of TCA cycle intermediates 13  It is the final pathway where the oxidative metabolism of carbohydrates, amino acids, and fatty acids converge, their carbon skeletons being converted to CO2. This oxidation provides energy for the production of the majority of ATP in most animals, including humans. The TCA cycle is an aerobic pathway, because O2 is required as the final electron acceptor. 14  The citric acid cycle also supplies intermediates for a number of important synthetic reactions. For example, the cycle functions in the formation of glucose from the carbon skeletons of some amino acids, and it provides building blocks for the synthesis of some amino acids and heme. 15  Energy Production by the TCA Cycle O Total energy yield from TCA is 12 ATP/acetyl CoA molecule oxidation. Regulation of the TCA cycle The TCA cycle is controlled by the regulation of several enzyme activities. The most important of these enzymes are: Citrate synthase, Isocitrate dehydrogenase, α- ketoglutarate dehydrogenase complex. 16 Excess Carbohydrates are Converted to Fat Excess calories are deposited as neutral fat in adipose tissue. The pathway is glucose to pyruvate to acetyl CoA to fatty acid which bind glycerol to form triacylglycerol (neutral fat) that stored in adipose tissues. 17 No Net Synthesis of Carbohydrates from Fatty acids Fatty acids through beta oxidation, are broken down to acetyl CoA and then enters CAC. Acetyl CoA entering the cycle is completely oxidized to CO2 by the time circle reaches succinyl CoA. So, acetyl CoA is completely broken down in the cycle. Thus, acetyl CoA cannot go for gluconeogenesis. Because convert to co and irrevisble Therefore, there is no net synthesis of carbohydrates from 18 fatty acids. Reference Book: Champe, P. C., Harvey, R. A. and Ferrier, D. R., 2005. Biochemistry “Lippincott’s Illustrated Reviews”, 5th or 6th Edition 19