بسم الله الرحمن الرحيم Kreb’s Cycle ( Tricarboxylic acid cycle (TCA) (Citric Acid Cycle By Ust / Rawda Ali Obeid
Objectives of the presentation Definition of citric acid cycle. Biomedical importance. Oxidation of pyruvate. Reaction of citric acid cycle. Sources of oxaloacetate. CO2 Produced is used in the following
The Citric acid cycle It is called the Krebs cycle or the tricarboxylic . The citric acid cycle is the final common pathway for the oxidation of fuel molecules: amino acids, fatty acids, & carbohydrates to produce ATP, CO2 and H2O. Occur in mitochondrial matrix
BIOMEDICAL IMPORTANCE The Citric acid cycle It also has a central role in gluconeogenesis, lipogenesis , and interconversion of amino acids ( Amphibolic pathways. Many of these processes occur in most tissues, but the liver is the only tissue in which all occur to a significant extent.
The repercussions are therefore profound when, for example, large numbers of hepatic cells are damaged as in acute hepatitis or replaced by connective tissue ( as in cirrhosis ). Very few, if any, genetic abnormalities of citric acid cycle enzymes have been reported; such abnormalities would be incompatible with life or normal development .
The citric acid cycle enzymes are found in the matrix of the mitochondria In the presence of O₂ pyruvate (the end product of glycolysis ) passes by special transporter into Mitochondria which proceeds as follows: Oxidative decarboxylation of pyruvate to acetyl CoA
EOC Problem 5: NAD + in oxidation and reduction reactions (a through f should be easy). Oxidation of pyruvate NADH:2X3= 6ATP
Energy production: Oxidative decarboxylation of pyruvate to acetyle CoA produces one molecule of NADH-H ⁺. This produces 3 ATP molecules through respiratory chain phosphorylation .
Reactions of Citric Acid Cycle 1-Citrate synthase :
2. Aconitase :
3. Isocitrate dehydrogenase :
4. a - Ketoglutarate dehydrogenase :
5. Succinyl CoA synthatse :
6. Succinate Dehydrogenase :
7. Fumarase :
8. L- Malate dehydrogenase :
Sources of oxaloacetate Oxidation of malate Transamination of aspartate Carboxylation of pyruvate Cleavage of citrate
CO2 Produced is used in the following Pyruvate + CO2 to form oxaloacetate which enter in gluconeogenesis . Acetyl CoA + CO2 to form malonyl CoA which enter in fatty acids synthesis. Ammonia +ATP+ CO2 to form carbamoyl phosphate which enter in the formation urea & pyrimidine . Formation of C6 of purine .
Energy production of TCA: Enzyme Isocitrate dehydrogenase NADH+H 3 ATP Ketoglutrate dehydrogenase NADH+H 3 ATP Succinyl CoA thiokinase GTP 1 ATP Sucssnate dehydrogenase FADH 2 ATP Malate dehydrogenase NADH+H 3 ATP total 12 ATP
ATP FROM GLYCOLYSIS Activation of glucose = - 2ATP Oxidation of 2NADH+H = 6ATP ADP phosphorylation (2 triose ) = 4ATP net of ATP from aerobic glycolysis = 8ATP
ATP FROM GLUCOSE One glucose molecule undergoing complete oxidation provides: From glycolysis = 8 ATP From 2 Pyruvate = 6 ATP From 2 Acetyl CoA = 24 ATP Net of ATP = 38 ATP
Functions of TCA : Catabolism Energy production from carbohydrates, lipids, amino acids Anabolism CAC intermediates are important in synthesis of Fatty acids Ketone bodies Cholesterol Amino acids Gluconeogenesis