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Overview of Gluconeogenesis: Key Pathways and Regulation in Glucose Metabolism

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This document provides a comprehensive overview of gluconeogenesis, highlighting its critical role in glucose production, particularly in the liver and kidneys. It outlines the main reactions and rate-limiting enzymes involved, insisting on the energy-consuming nature of this anabolic pathway. Important gluconeogenic substrates such as glycerol, lactate, and glucogenic amino acids are discussed, alongside the regulatory mechanisms that govern the balance between gluconeogenesis and glycolysis. Its significance in metabolic processes offers insights essential for medical biochemistry and pathology.

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Overview of Gluconeogenesis: Key Pathways and Regulation in Glucose Metabolism

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  1. بسم الله الرحمن الرحيم

  2. Glucose Metabolism: Gluconeogenesis By Amr S. Moustafa, MD, PhD Assistant Prof. & Consultant, Medical Biochemistry Unit, Pathology Dept., College of Medicine, KSU amrsm@ksu.edu.sa

  3. Objectives • The importance of gluconeogenesis as an important pathway for glucose production • The main reactions of gluconeogenesis • The rate-limiting enzymes of gluconeogenesis • Gluconeogensisis an energy-consuming, anabolic pathway

  4. Gluconeogenesis: An Overview • Liver (mainly) and Kidneys • Both mitochondria and Cytosol • Exception: Glycerol, only cytosol • Gluconeogenic substrates: • Glycerol • Lactate and Pyruvate • Glucogenic amino acids

  5. GluconeogenicPathway Dephosphorylation of G-6-P Dephosphorylation of F 1,6-P Transport of OAA Carboxylation of pyruvate

  6. GluconeogenicSubstrates: Glycerol *GK Glycerol Glycerol 3-phosphate ATP ADP NAD+ Glycerol 3-phosphate dehydrogenase NADH Glucose Dihydroxyacetone phosphate *GK: Glycerol kinase only in liver & kidneys

  7. Glucogenic Amino Acids Asp Asn Amino acids Glu, Gln Phe Tyr Met Val

  8. Lactate Gluconeogenic Substrates Gly, Ala Amino acids Pyruvate Asp Asn Amino acids Glu, Gln Phe Tyr Met Val

  9. GluconeogenicSubstrates: Lactate(Cori Cycle)

  10. GluconeogenicPathway Dephosphorylation of G-6-P Dephosphorylation of F 1,6-P Transport of OAA Carboxylation of pyruvate

  11. Pruvate Carboxylase and PEP-CK Fasting: Acetyl CoA (FAO) OAA (Gluconeogensis) Pyruvate carboxylase + PEP-CK = Pyruvate kinase

  12. Fructose 1,6-Bisphosphatase Fructose 1,6-bisphosphatase = PFK-1

  13. Glucose 6-Phosphatase Glucose 6-phosphatase = Glucokinase

  14. Gluconeogensis:E- Consumed Six High-Energy Phosphate Bonds From Pyruvate to Glucose 2 ADP 2 ATP

  15. Gluconeogenesis: Regulation • Reciprocal control • Gluconeogenesis & Glycolysis • Allosteric: • Acetyl CoA(Pyruvate carboxylase) • AMP or ATP • F 2,6-Bisphosphate • Glucagon ( I/G ratio) • Allosteric ( F 2,6-Bisphosphate) • Induction (PEP-CK) F 1,6-bisphosphatase

  16. Take Home Message • Gluconeogenesis: • Synthesis of glucose from noncarbohydrates • Anabolic • Energy-consuming • 4 Unique enzymes are required for • reversal of the 3 irreversible reactions • of glycolysis • Both gluconeogenesis & glycolysis are • reciprocally-regulated

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