Glycolysis Definition Fx Fate Site Intracellular location Rate limiting steps Regulation Consume ATP Subs level phosphoryla tion Key reactions control points Nb Oxidation of glucose to give pyruvate ( in the presence of oxygen ) or lactate ( in the absence of oxygen ) To produce pyruvate for energy production Anaerobically : lactate Aerobically: acetyl Coa à enter Kreb s Cycle All tissue cell, but it is physiological importance in: a) Tissues with no mitochondria: RBC b) Tissues with few mitochondria: testes and leukocytes c) Tissues undergo frequent oxygen lack: skeletal muscle especially during exercise Cytosol Hormonal control 1. Insulin : secreted after CHO feeding & in response to blood glucose. - Inducer for glycolytic key enzyme 2. Glucagon : secreted during CHO deficiency & in response to blood glucose - Repressor of glycolytic key enzyme 1. G G 6 P 2. F 6 P F 1,6 BP 1. 1 3 PG 3 PG 2. PEP Pyruvate Hexokinase/glucokinase : G G,6 P Phosphofructokinase: F 1,6 B F 6 - P Pyruvate kinase : PEP Pyruvate Oxidation 1. Add CO2 2. Remove H 3. Add +ve 4. Remove ve Overall rxn Glucose + 2ADP + 2Pi + 2 ATP + 2NAD 2 Pyuravate + 2NADH + H+ + 4ATP +2H20 PHASES PHASE 2 PHASE 1 Energy production ATP PRODUCED (++) ATP UTILIZED ( - - ) NET ENERGY Anaerobic 4ATP 2ATP from 1-3 GP 2ATP from PEP 2ATP G G6P F6P F1,6P 2 ATP - 2 + 4 = 2ATP Aerobic 4ATP 2ATP from 1-3 GP 2ATP from PEP 4ATP or 6ATP NADHH = 3 ATP MAS FADH2 = 2 ATP GPS 2ATP G G6P F6P F1,6 6P 6 ATP or 8 ATP - 2 + 4 + 4 = 6ATP, MAS - 2 + 4 + 6 = 8ATP, GPS
Aerobic glycolysis Anaerobic glycolysis Site Cytoplasm of all tissues RBCs, Medulla of kidney, Lens, Cornea, testes and skeletal muscle during muscular exercise End product Pyruvic acid + NADHH+ Lactic acid + NAD+ Energy production 6 or 8 ATP 2 ATP Lactate dehydrogenase Not needed Needed HEXOKINASE Most tissue High affinity to glucose Low Km, Vmax 0.1 mm For all hexose ( glucose, galactose, fructose ) by ve feedback ( G6P ) GLUCOKINASE Liver parenchymal, B cells of pancreas Low affinity to glucose High Km, Vmax 10mm As a glucose sensor by enhancing insulin secretion from pancreatic B cells and glucose metabolism in liver For glucose only No effect by ve feedback Isomerase Epimerase Mutase Change aldehyde ketone Change aldehyde aldehyde or ketone ketone Change the number Energy signals regulate glycolytic pathway Stimulate Inhibit AMP, ADP, NAD ATP, NADH Glycolysis Glucokinase Phosphofructokin ase 1 Pyruvate kinase Gluconeogenesis Glucose 6 phosphatase Fructose 1,6 bisphosphotase Pyruvate carboxylase Phosphoenol pyruvate carboxykinase
Gluconeogenesis Definition Synthesis of new glucose from non CHO source ( day fasting ) Site Cytoplasm and mitochondria of liver and kidney Source Glycerol Pyruvate, propionic acid Amino acid ( glutamic, aspartic, alanine ) Lactate Intermediate of TCA Regulation Importance Hormonal 1. Insulin : repressor of gluconeogenesis key enzymes, inducer of glycolytic key enzyme 2. Anti insulin ( glucagon, epinephrine, glucocorticoids ) : increase in activity of gluconeogenesis key enzyme. Glucocorticoids acts as inducer for gluconeogenesis key enzyme Acetyl CoA and ATP 1. ++ gluconeogenesis, - - glycolysis 2. ++ pyruvate carboxylase, - - - pyruvate dehydrogenase 1. Maintenance of blood glucose, when CHO are not available, in sufficient amount in fasting, starvation, stress, prolonged exercise, and dietary CHO deficiency. Brain, RBCs, lens of eye, cornea, kidney medulla, exercising muscles and testes require a continuous supply of glucose 2. Removal of lactic acid produced by red cells and contracting muscles 3. Removal of glycerol produced by lipolysis and adipose tissue Key enzyme ü Carboxylase : +1c Carboxykinase: - 1c, +1p ü Phosphatase: - 1p Glucose 6 phosphatase: - 1p Require energy Reciprocal control with glycolysis From pyruvate Pyruvate OAA (- 2ATP) OAA PEP (- 2GTP) 3PG 1,3 BPG (- 2ATP) From glycerol Glycerol enters the gluconeogenic pathway at the DHAP level. Conversion of glycerol to glycerol 3- phosphate, which is oxidized to DHAP. (- 1ATP) Glycolysis on, gluconeogenesis off Energy status high, glycolysis off à pyruvate use for synthesis and storage of glucose Energy status low, glycolysis on à glucose rapidly degrade to provide energy