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Chapter 16 Citric acid cycle

Chapter 16 Citric acid cycle. (read entire chapter). Learn to draw the TCA cycle, including the names and structures of intermediates and the names of the enzymes. Citric acid cycle also known as the tricarboxylic acid (TCA) cycle or the Krebs cycle. After Glycolysis. What next …….

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Chapter 16 Citric acid cycle

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  1. Chapter 16 Citric acid cycle (read entire chapter) Learn to draw the TCA cycle, including the names and structures of intermediates and the names of the enzymes.

  2. Citric acid cycle also known as the tricarboxylic acid (TCA) cycle or the Krebs cycle

  3. After Glycolysis What next …… Glucose + 2 ADP + 2 Pi + 2 NAD+ Glycolysis 2 Pyruvate + 2 ATP + 2 NADH + 2 H+ + 2 H2O • Cell must regenerate the NAD+ that was utilized in glycolysis. • NAD+ regeneration can be accomplished by aerobic or anaerobic metabolism

  4. Three possible fates of pyruvate Aerobic Metabolism Pyruvate NADH + H+ Anaerobic metabolism Lactate dehydrogenase Acetaldehyde NAD+ Acetyl CoA NADH + H+ Alcohol dehydrogenase L-lactate NAD+ Homolactic fermentation TCA cycle Ethanol Alcoholic fermentation Electron transport Adapted from Chemistry 153A UCLA Course Compendium by M. A. Bates

  5. Aerobic Metabolism Pyruvate dehydrogenase complex A cluster of 3 enzymes located in the mitochondria of eukaryotic cells and cytosol of prokaryotes A classic well studied example of a multienzyme complex Non-covalent stable aggregate of enzymes From Lehninger Principles of Biochemistry

  6. Overall reaction catalyzed by the pyruvate dehydrogenase complex Oxidative decarboxylation Irreversible reaction Requires sequential action of - 3 different enzymes & 5 different coenzymes From Lehninger Principles of Biochemistry

  7. Different Coenzymes or Prosthetic Groups Required for Pyruvate Dehydrogenase Complex are: • Thiamine pyrophosphate (TPP) • Flavin adenine dinucleotide (FAD) • Coenzyme A (CoA) • Nicotinamide adenine dinucleotide (NAD+) • Lipoate Four different vitamins required in human nutrition are vital components of this system Thiamine (in TPP) Riboflavin (in FAD) Niacin (in NAD) Pantothenate (in CoA)

  8. Thiamine pyrophosphate (TPP) From Lehninger Principles of Biochemistry

  9. Ethanol fermentation in yeast and other microorganisms From Lehninger Principles of Biochemistry

  10. 2. Flavin adenine dinucleotide (FAD) From Lehninger Principles of Biochemistry

  11. 3. Coenzyme A (CoA) Critical to its role as an acyl carrier (vitamin B5) Hydroxyl group of pantothenic acid is joined to ADP moeity Modified ADP Carboxylic group attached to b-mercaptoethylamine From Lehninger Principles of Biochemistry

  12. 4. Nicotinamide adenine dinucleotide (NAD+) From Lehninger Principles of Biochemistry

  13. 5. Lipoate Lipoate has 2 thiol groups Lipoyllysyl moiety is the prosthetic group of dihydrolipoyl transacetylase (E2) From Lehninger Principles of Biochemistry

  14. Pyruvate Dehydrogenase Complex • Consists of 3 distinct enzymes: 1) Pyruvate dehydrogenase (E1) 2) Dihydrolipoyl transacetylase (E2) 3) Dihydrolipoyl dehydrogenase (E3) • The 3 enzymes are bound together in stable, non-covalent aggregates. • Each enzyme is present in multiple copies within each aggregate. • The # of copies of each enzyme & the actual size of the complex varies among organisms.

  15. Pyruvate Dehydrogenase Complex from E. coli • E2 forms the core of the cluster to which • other enzymes are attached • E2 24 copies Contains bound lipoate • E1 24 copies Contains bound TPP • E3 12 copies Contains bound FAD

  16. Overall reaction catalyzed by the pyruvate dehydrogenase complex Oxidative decarboxylation Irreversible reaction Requires sequential action of - 3 different enzymes & 5 different coenzymes From Lehninger Principles of Biochemistry

  17. Mechanism of Pyruvate Decarboxylase

  18. Aerobic oxidation of glucose that includes • the oxidation of pyruvate provides • energy in the brain • Thiamine (vitamin B1) deficiency • - Unable to oxidize pyruvate normally • Beriberi, a disease that is characterized by • loss of neural function is due to thiamine • deficiency Habitual consumption of large amounts of alcohol can lead to thiamine deficiency

  19. Beriberi - caused by a deficiency of thiamine (vitamin B1) - affects the muscles, heart, nerves, and digestive system - literally means "I can't, I can't" in Singhalese, which reflects the crippling effect it has on its victims - common in parts of the developing world, where white rice is the main food www.nlm.nih.gov/medlineplus

  20. Catabolism of proteins, fats, and carbohydrates in the three stages of cellular respiration • Glycolysis - cytosol • Fatty Acid Oxidation: Inner matrix of mitochondria • Citric Acid Cycle: Inner matrix of mitochondria • Oxidative Phosphorylation: Inner membrane of mitochondria From Lehninger Principles of Biochemistry

  21. The Citric Acid Cycle has Eight Steps From Lehninger Principles of Biochemistry

  22. Reactions of the citric acid cycle Steps 1, 3, & 4 irreversible 4 out of 8 steps are oxidations Energy is conserved by electron transfer to FAD or NAD+, forming FADH2 or NADH + H+ All of these reactions take place in mitochondria From Lehninger Principles of Biochemistry

  23. The TCA Cycle aka Citric Acid Cycle, Krebs Cycle • Pyruvate (actually acetate) from glycolysis is degraded to CO2 • Some ATP is produced • More NADH is made • NADH goes on to make more ATP in electron transport and oxidative phosphorylation

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