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بسم الله الرحمن الرحيم

بسم الله الرحمن الرحيم. Glucose Metabolism: Glycolysis. By. Reem M. Sallam, M.D.; Ph.D. Assistant Prof., Clinical Chemistry Unit, Pathology Dept. College of Medicine, KSU sallam@ksu.edu.sa. Glycolysis: Revision. Major oxidative pathway of glucose

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بسم الله الرحمن الرحيم

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  1. بسم الله الرحمن الرحيم

  2. Glucose Metabolism: Glycolysis By Reem M. Sallam, M.D.; Ph.D. Assistant Prof., Clinical Chemistry Unit, Pathology Dept. College of Medicine, KSU sallam@ksu.edu.sa

  3. Glycolysis: Revision • Major oxidative pathway of glucose • The main reactions of glycolytic pathway • The rate-limiting enzymes/Regulation • ATP production (aerobic/anaerobic) • Pyruvatekinase deficiency hemolytic anemia

  4. Long-Term Regulation of Glycolysis • Hormones can regulate glycolysis in a slow but long-term manner. • Insulin  induction of glucokinase, PFK-1, & PK in liver  increase gene transcription  increase enzyme synthesis. • High glucagon  decreased gene expression rate of glucokinase, PFK-1 & PK

  5. Anaerobic Glycolysis • Lactate is the final product of anaerobic glycolysis. • It is the result of reduction of pyruvate to lactate by lactate dehydrogenase (LDL). It is reversible reaction, so not regulated. • Why is Lactate an obligatory end product under anaerobic conditions? (because if this step did not happen the cellular content of NAD+ will be all used up) • During Anaerobic glycolysis: NADH produced cannot be used by ETC for ATP production (due to either decrease in O2 and/or lack of mitochondria) • NADH is reoxidized to NAD+ by the conversion of pyruvate to lactate) • Less ATP production, as compared to aerobic glycolysis

  6. Anaerobic Glycolysis: ATP Production ATP Consumed: 2 ATP ATP Produced: Substrate-level 2 X 2 = 4 ATP Oxidative-level 2 X 3 = 6 ATP Total 4 ATP Net:4 – 2=2 ATP

  7. Glycolysis in RBCs: ATP Production ATP Consumed: 2 ATP ATP Produced: Substrate-level 2 X 2 = 4 ATP 1 X 2 = 2 ATP Oxidative-level 2 X 3 = 6 ATP Total 4 OR 2 ATP Net:4 – 2=2 ATP 2 – 2 = 0 ATP OR OR

  8. Glycolysis in RBCs: Summary End product: Lactate No net production or consumption of NADH Energy yield: If no 2,3-BPG is formed: 2 ATP If 2,3-BPG shunt occurs: 0 ATP PK Deficiency hemolytic anemia depends on: Degree of PK Deficiency Compensation by 2,3-BPG

  9. Take Home Message • Glycolysis is the major oxidative pathway for • glucose • Glycolysis is employed by all tissues • Glycolysis is a tightly-regulated pathway • PFK-1 is the rate-limiting regulatory enzyme

  10. Take Home Message • Glycolysis is mainly a catabolic pathwayfor ATP production, But it has some anabolic features (amphibolic) • Pyruvatekinase deficiency in RBCs results in hemolytic anemia

  11. Take Home Message • Net energy produced in: • Aerobic glycolysis: 8 ATP • Anaerobic glycolysis: 2 ATP • Net energy produced in glycolysis in RBCs: • Without 2,3 BPG synthesis: 2 ATP • With 2,3 BPG synthesis: 0 ATP

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