Glucose Metabolism Lecture 2 PDF

Introduction of Glucose Metabolism Lecture-2 Glycolysis  Glycolysis Glycolysis is the breakdown of glucose to: 1- Provide energy in the form of ATP (main function) 2- Provide intermediates for other metabolic pathways. It occurs in cytosols of all tissue...

Introduction of Glucose Metabolism Lecture-2 Glycolysis  Glycolysis Glycolysis is the breakdown of glucose to: 1- Provide energy in the form of ATP (main function) 2- Provide intermediates for other metabolic pathways. It occurs in cytosols of all tissues All sugars can be converted to glucose & thus can be metabolized by glycolysis.  Overall reactions of glycolysis Thekeyregulatory Regulatory enzyme -Glucose Glucose Fructose Dihydroxy acetone enzyme -6-phosphate (Theratelimiting Fructose-1,6- bisphosphate -6-phosphate (Fructose-1,6-diphosphate) phosphate (DHA P) CH2OH enzyme) Glucokinase CH2O P O H or H Phosphohexose CH2O P CH2OH Phosphofructo- 6 CH O P 1 Aldolase A CH2 O P O 2 CH2O P OH Hexokinase isomerase O kinase (PFK) C O OH O OH Mg2+ HO Mg 2+ 5 HO 2 CH2OH OH OH OH 4 OH ATP ADP 3 OH OH ATP ADP OH OH OH Phosphotrios isomerase High energy From bond inorganic (unstable) phosphate 2 Steps: O  Oxidation: CHO COOH H O (Substrate level phosphorylation) COOH  C  Phosphorylation: COOH  COOP Phosphoglycerate Kinase C O P 2 H C OH 2 H C OH 2 H C OH Glyceraldehyde-3-phosphate dehydrogenase CH2 O P CH2 O P Mg2+ Pi CH2 O P Glyceraldehyde 2 ATP 2 ADP 3-Phospho glyceric acid 1,3- Bisphospho glycerate +H+ 2 NADH 2 NAD -3-phosphate (1,3- diphospho glyceric acid) Mitochondria Phosphoglycerate Aerobic glycolysis Mutase H2O2 (Substrate level phosphorylation) 3 ADP+3 Pi 3 ATP Regulatory enzyme COOH P COOH Pyruvate COOH COOH +H+ 2 NAD 2 NADH 2 P Enolase 2 C O kinase COOH 2 2 H C O C OH C O CH2 OH Mg2+ CH2 Mg2+ CH2 CH3 Lactate 2 CH OH Anaerobic Phospho enolpyruvate CH3 glycolysis 2-Phospho glycerate (PEP) 2 ADP 2 ATP Pyruvate dehydrogenase (LDH) H2O Ketopyruvate Lactate Reduction  End products of glycolysis AEROBIC GLYCOLYSIS Mitochondria & Oxygen NADH ANAEROBIC GLYCOLYSIS is an end product No mitochondria of aerobic glycolysis No Oxygen Or Both Lactate is the end product of anaerobic glycolysis Pyruvate is the end product of aerobic glycolysis  End products of glycolysis 1- In cells with mitochondria & an adequate supply of oxygen (Aerobic glycolysis) - 2 Pyruvate: enters the mitochondria & is converted into acetyl CoA. Acetyl CoA enters citric acid cycle (Krebs cycle) to yield energy in the form of ATP - 2 NADH: utilizes mitochondria & oxygen to yield energy 2- In cells with no mitochondria or adequate oxygen (or Both) (Anaerobic glycolysis) 2 Lactate: formed from pyruvate (by utilizing NADH)  Energy yield from glycolysis 1- Anerobic glycolysis 2 molecule of ATP for each one molecule of glucose converted to 2 molecules of lactate It is a valuable source of energy under the following conditions 1- Oxygen supply is limited as in skeletal muscles during intensive exercise 2- Tissues with no mitochondria RBCs 3- others: Kidney medulla Leukocytes Lens & cornea cells Testes 2-Aerobic glycolysis 2 moles of ATP for each one mol of glucose converted to 2 moles of pyruvate 2 molecules of NADH for each molecule of glucose 3 ATPs for each NADH entering electric transport chain (ETC) in mitochondria.  Energy yield from glycolysis In anaerobic glycolysis: 2 ATP for one glucose molecule In aerobic glycolysis 2 ATP 2NADH 2Pyruvate 2 Acetyl CoA 2 NADH: 2 X 3 = 6 ATP Total= 2+ 6 = 8 ATP Complete aerobic oxidation of glucose: 2 pyruvate convert to 2 acetyl coA= 6ATP 2 Acetyl Co A which enter in citric acid cycle: 2 X 12 = 24 ATP  Energy yield of Energy yield of aerobic GLUCOSEanaerobic glycolysis Netglycolysis = 8 ATP / glucose Net = 2 ATP/ glucose molecule molecule +2NAD ATP 2 2 No Oxygen No Oxygen NADH Mitochondria & X3= 2= OR BOTH Mitochondria 6 ATP 2 Lactate 2 +2NAD PYRUVATE 2 NADH X 3 = 2 = ACETYL CoA 2 6 ATP Energy yield of CITRIC ACID CYCLE aerobic X 12 = 24 ATP 2 = oxidation t = 38 ATP / glucose molecule Regulation of glycolysis Glucokinase By Insulin & Glucagon By Insulin & Glucagon Key enzymes in glycolysis Long-term Regulation of glycolysis Induction & Repression of enzymes synthesis Insulin: Induction Glucagon: Repression  Genetic defects of glycolytic enzymes Pyruvate kinase deficiency - Pyruvate kinase (PK) deficiency leads to a reduced rate of glycolysis with decreased ATP production. - PK deficiency effect is restricted RBCs. As RBCs has no mitochondria & so get ATP only from glycolysis. RBCs needs ATP mainly for maintaining the bio- concave flexible shape of the cell. - PK deficiency leads to severe deficiency of ATP for RBCs. So, RBCs fail to maintain bi-concave shape ending in liability to be lysed (hemolysis). Excessive lysis of RBCs leads to chronic hemolytic anemia.  Importance of glycolysis 1-It is the principle route for glucose metabolism for ATP production. 2-It is the only source of energy for RBCs and contracting muscles. 3-It provides mitochondria with pyruvic acid which gives acetyl CoA needed for Kreb's cycle. 4-In RBCs, it gives 2, 3 DPG -2, 3 DPG lowers O2 affinity by hemoglobin, so it increases dissociation of O2 to the peripheral tissues