Krebs Cycle Biochemistry Notes PDF

BIOCHEMISTRY KREB’S CYCLE Prepared by: Zen and ++ Lecturer: Farr Krizha I. Tangkusan, RN, MD SEPTEMBER 25, 2024 Which step is rate-limiting? CITRIC ACID CYCL...

BIOCHEMISTRY KREB’S CYCLE Prepared by: Zen and ++ Lecturer: Farr Krizha I. Tangkusan, RN, MD SEPTEMBER 25, 2024 Which step is rate-limiting? CITRIC ACID CYCLE Isocitrate → α-ketoglutarate Kreb’s cycle or tricarboxylic acid cycle ENZYME: isocitrate dehydrogenase Final common pathway for the aerobic oxidation of carbohydrates, lipids, and proteins Citrate Synthase Recall that, Kreb’s cycle is AMPHIBOLIC Kreb’s Cycle What is it for? ✓ Major pathway for formation of ATP ✓ Also provides substrates for gluconeogenesis, amino acid synthesis, and fatty acid synthesis Condensation of Acetyl-CoA with OAA Where does it occur? Citrate: also used as transporter of Acetyl-CoA ✓ In all cells with mitochondria ◦ Fatty acid and cholesterol synthesis ✓ Mitochondrial matrix Citrate: inhibits PFK-1 ▪ Except: succinate dehydrogenase (inner mitochondrial membrane) What is the substrate? ✓ Acetyl CoA What are the end-products? ✓ 2 CO2, 1 GTP, 3 NADH, 1 FADH2 Biochemistry Prepared by: Zen and ++ September 25, 2024 BIOCHEMISTRY KREB’S CYCLE Prepared by: Zen and ++ Lecturer: Farr Krizha I. Tangkusan, RN, MD SEPTEMBER 25, 2024 ◦ (+): Isocitrate, ADP Aconitase ◦ (-): NADH, ATP Yields CO2 and NADH Requires: Mg2+ or Mn2+ α-ketoglutarate Important metabolite of TCA Non-heme iron protein ◦ Anaplerotic metabolite that links TCA to ◦ Contains inorg. Fe and S → iron-sulfur centers amino acid metabolism (complexed with Cys) ◦ Important part of malate-aspartate shuttle Isomerization of Citrate to Isocitrate system Inhibited by Isocitrate and fluoroacetate (pesticides) Isocitrate Dehydrogenase α-ketoglutarate Dehydrogenase Complex Oxidative decarboxylation of α-ketoglutarate Oxidative decarboxylation of Isocitrate to α- to Succinyl-CoA ketoglutarate Yields CO2 and NADH Rate-limiting step of TCA Biochemistry Prepared by: Zen and ++ September 25, 2024 BIOCHEMISTRY KREB’S CYCLE Prepared by: Zen and ++ Lecturer: Farr Krizha I. Tangkusan, RN, MD SEPTEMBER 25, 2024 Similar to pyruvate dehydrogenase complex Bound to the inner surface of inner mitochondrial Inhibited: increase NH3 and Arsenite membrane Contains FAD and Fe-S protein Succinyl-CoA Synthetase Oxidation of Succinate to Fumarate Yields FADH2 Fumarase “Succinyl-CoA ligase”, “Succinate thiokinase” Yields 1 GTP (or ATP) → substrate level phosphorylation ◦ Depending on isoenzyme “Fumarate hydratase” Hydration of Fumarate to Malate (L-malate) Succinate dehydrogenase Malate dehydrogenase Oxidation of Malate to Oxaloacetate Yields NADH Highly endergonic reaction ◦ Coupled with condensation of OAA to Acetyl-coA Biochemistry Prepared by: Zen and ++ September 25, 2024 BIOCHEMISTRY KREB’S CYCLE Prepared by: Zen and ++ Lecturer: Farr Krizha I. Tangkusan, RN, MD SEPTEMBER 25, 2024 Steps that produce CO2 Steps that produce GTP ATP yields in Kreb’s Cycle Steps that produce NADH dehydrogenase Complete Oxidation of Glucose Steps that produce FADH2 Biochemistry Prepared by: Zen and ++ September 25, 2024 BIOCHEMISTRY KREB’S CYCLE Prepared by: Zen and ++ Lecturer: Farr Krizha I. Tangkusan, RN, MD SEPTEMBER 25, 2024 2. Transamination and deamination- these reactions produce pyruvate from Ala, oxaloacetate from Asp, and alpha-ketoglutarate from glutamic acid 3. Fatty acid synthesis- acetyl coA is the major building block for long chain fatty acid synthesis in nonruminants SUMMARY 1. Krebs cycle is amphibolic. It is both anabolic and catabolic 2. Acetyl coA is called as the central Regulations of Kreb cycle molecule of biochemistry. In well-fed 1. The rate of Kreb cycle depends upon two state, acetyl coA will come from factors glycolysis (pyruvate to acetyl coA by 1. Energy requirement of the cell pyruvate dehydrogenase). In fasting 2. Requirement of the cell for carbon state, acetyl coA will come from fatty precursors acids so beta oxidation of fatty acids which are converted to acetyl CoA Inhibitors of Kreb cycle 3. When Acetyl CoA enters kreb’s cycle, it 1. Arsenite a-Retighatanate - ->sucey/coA produces NADH, FADH and GTP. Its a 2. Fluoroacetate Acetul->WA iscitate high number of ATP molecules 3. Malonate succinate -> fumarate -> 4. Remember the names of enzymes where it came from The citric acid cycle plays a key role in the 5. Other functions of kreb’s cycle: following metabolic pathways gluconeogenesis (malate from kreb’s cycle will enter gluconeogenesis), citrate 1. Gluconeogenesis- all major members of the used for fatty acids synthesis, and kreb’s cycle, from citrate to oxaloacetate are succinyl CoA is used for heme synthesis potentially glucogenic (succinyl CoA will combine in glycine) Biochemistry Prepared by: Zen and ++ September 25, 2024 BIOCHEMISTRY KREB’S CYCLE Prepared by: Zen and ++ Lecturer: Farr Krizha I. Tangkusan, RN, MD SEPTEMBER 25, 2024 6. Remember the ATP yield. For every acetyl CoA molecule, 10 ATP’s are produced. So if you complete oxidize glucose, you get 30 to 32 ATP’s depending on the shuttle used 7. Finally, remember that kreb’s cycle takes place in the mitochondrial matrix except for succinate dehydrogenase step found in the inner mitochondrial membrane. Biochemistry Prepared by: Zen and ++ September 25, 2024