2- Glycolysis.pdf

CARBOHYDRATE METABOLISM Glycolysis Fate of dietary Sugars Provides Other Storage Glucose Oxidation Compounds Glycogen CHO, Lipid & A.A TAG  OXIDATION OF GLUCOSE Major pathway...

CARBOHYDRATE METABOLISM Glycolysis Fate of dietary Sugars Provides Other Storage Glucose Oxidation Compounds Glycogen CHO, Lipid & A.A TAG  OXIDATION OF GLUCOSE Major pathway Minor pathway Glycolysis Krebs’ cycle HMP Uronic acid pathway ETC  Reactions of Glycolysis Definition: oxidation of glucose to pyruvic acid (in presence of O2, Aerobic) or to lactic acid (in absence of O2, anaerobic) Site: cytosol of all cells Catabolism of 1 mol glc (6 C) produces 2 moles of pyruvate or lactate (3 C) Conversion of glucose to pyruvate occurs in 2 stages: energy investment phase (first five reactions) energy generation phase Lactate is produced only in: RBC  there is no mitochondria Exercising muscles  lack of O2  1. Phosphorylation of glucose Phosphorylated sugar molecules do not readily penetrate cell membranes (no carriers, too polar to cross) Irreversible phosphorylation of glucose Trapping traps it as cytosolic glc-6-P Activation Energy investment phase phosphorylation of glucose. Aldose-ketose isomerization of glc 6-P to fructose 6-P. Conversion of fructose 6-P to triose phosphates.  2X Energy generating phase: conversion of glyceraldehyde 3-phosphate to pyruvate. Energy gain in aerobic glcolysis Step 1 Glucokinase (GK) - 1 ATP Step 3 Phosphofructokinase - 1 ATP (PFK) Step 7 Phosphoglycerate kinase + 2 ATP Step 10 Pyruvate kinase (PK) + 2 ATP Step 6 2 NADH + 5 ATP Net gain + 7 ATP  Energy gain in anaerobic glycolysis Step 1 Glucokinase (GK) - 1 ATP Step 3 Phosphofructokinase (PFK) - 1 ATP Step 7 Phosphoglycerate kinase + 2 ATP Step 10 Pyruvate kinase (PK) + 2 ATP Net gain + 2 ATP Glycolysis Importance of Glycolysis I- Energy production A- Under aerobic state: 2 NADH (5 ATP) + 4 ATP - 2 ATP 7 ATP Glyceraldehyde 3-P Phosphoglycerate kinase dehydrogenase Pyruvate kinase B- Under anaerobic state: 4 ATP - 2 ATP 2 ATP Phosphoglycerate kinase Pyruvate kinase Glycolysis Importance of Glycolysis II- In Erythrocytes - Glycolysis is the only source of ATP - Source of 2,3 BPG (phosphoglycerate shunt) III- Important 1 Intermediates: TAG 3 DHAP G3-P 2 3-Phosphoglycerate Serine Phospholipids Glycolysis Clinical applications of Glycolysis 1. Glyceraldehyde-3-phosphate dehydrogenase: Arsenite (arsenic poisoning) and iodoacetate SH group 2. Enolase: Fluoride Inhibits glycolysis by Mg2+ chelation Glucose estimation 3. Pyruvate Kinase: The most common (95%) deficient E in inherited enzymopathies of RBCs Glycolysis Regulation of Glycolysis Key Enzymes Glucokinase (GK) or hexokinase (HK) Phosphofructokinase-1 (PFK-1) Pyruvate kinase (PK) Allosteric Hormonal Regulation of Glycolysis 1- Glucokinase & Hexokinase Glucokinase Hexokinase (Hexokinase IV) Site Most tissues Liver and pancreatic β cells Glucose mainly and Glucose mainly and Substrate other hexoses other hexoses Has a low Km i.e. high affinity Has a high Km i.e. low affinity Affinity to glucose for glucose and low Vmax. for glucose and high Vmax. Effect of : - Insulin No Effect Inducer - Glucagon No Effect Repressor - Fasting No Effect Decreases the activity - Feeding of glucose No Effect Increases the activity Glycolysis Regulation of Glycolysis Allosteric 1- Glucokinase (GK ) Hexokinase (HK) Q Liver & Pancreas contain Glucokinase (HK-D) isoenzyme  Allosteric 2- Phosphofructokinase-1 (PFK-1) The most important control site (1st irreversible R unique to glycolysis)  PFK  rate limiting enzyme (+) 3- Pyruvate kinase (PK) Short Term ( P / De P ) (min-hrs) Glycolysis Regulation of Glycolysis Hormonal Insulin / Glucagon Long Term (Synthesis ) Glycolysis Regulation of Glycolysis Effect of Fatty Acid Oxidation  F.A oxidation rate of glycolysis Minimize Glc oxidation during fasting or CHO deprivation, which allows more glucose for the brain.  F.A oxidation ATP PFK-1 and pyruvate kinase  F.A oxidation Acetyl CoA citrate PFK-1  MATCH (a) [ATP] < [AMP] ______ 1. Inhibits phosphofructokinase in the liver (b) Citrate ______ 2. Glucokinase (c) Insulin ______ 3. GLUT2 (d) Has a high Km for glucose…… 4. Inhibits phosphofructokinase (e) Transporter specific to liver and 5. Causes the insertion of GLUT4 into cell pancreas…… membranes (f) [ATP] > [AMP] 6. Stimulates phosphofructokinase