Oxidation of Glucose There are two pathways for oxidation of glucose. 1) Major pathways: 1) Glycolysis. 2) Kreb's cycle. 2) Minor pathway: Pentose shunt Glycolysis (anaerobic phase of glucose oxidation) Definition : it is the oxidation of glucose or glycogen in to pyruvic acid in presence of O2 or lactic acid in lack of oxygen (in muscular exercise and RBCs in absence of mitochondria (RBCs,cornea,eye lens),or tissue with few mitochondria, testis, leucocytes, medulla of kidney, retena, skin and GIT) Comment on glycolysis 1) it proud the mitochondria whith pyruvic acid which give oxaloacetate (the beginning of kreb's) 2) the phosphorylation of (G) is catalyzed by hexokinase or glycokinase . Pyruvate dehydrogenase deficiency it produce Anemia. *All reactions are reversable exept: 1) hexokinase 2) phosphofructokinase 3) pyruvate kinase [Biological oxidation ] Glucose oxidation 1- glycolysis: it is the oxidation of glucose to give pyruvat in the presence of oxygen or lactate in absence of O2 site : in cytoplasm of all tissues * Tissues with no or little mitochondria , mature RBC, cornea, lens , retina skeletal muscles depend mainly of glycolysis. Stage of glycolysis: 1- Energy requiring stage. one molecule of glucose is converted into 2 moles of glyceraldehydes 3 - PO4 these steps requires 2 ATP ( energy loss ) 2-energy producing stage: a) the 2 moles of glyceraldehydes – 3 -PO4 are converted into pyruvate (aerobic glycolysis) or lactate ( anaerobic glycolysis). * steps produce ATP Energy ATP production of glycolysis ATP production of glycolysis: ATP production = ATPproduced – ATP ultize ATP production = 4 ATP – 2 ATP = 2 ATP 4 ATP from 2 glyceradehde by sybstrate level phosphorylation Oxidation of extra mitochondrial NADH+ + H+, Cytoplasmic NADH+ + H+ cannot penetrate mitochondria membrane , it can be used to produce energy (4 or , 6ATP) by respiratory chain phosphorylation in the mitochondria. * this can be done by using special carrier . 2ATP + 2NADH+H 8 ATP 2ATP + 2X3 ATP 8ATP In tissue with no or little mitochondria or leak in oxygen ATP=2 only not 8 Tricarboxylic acid cycle (TCA) Citric acid cycle -Aerobic phase of glucose oxidation In presence of oxygen pyruvate from glycolysis enter mitochondria to be oxidized to CO2+H2O+Energy. So citric acid cycle is aseries of reactions in mitochondria aim to catabolism of active acetate,liberating hydrogen equivalent which upon oxidation give most of free energy to tissue (fuel). CH3C-COOH pyruvate dehydrogenase CH3C- SCOA active acetate Complex NAD,FAD,TPP,COASH,LIPOIC acid CH3C-COOH pyruvate CH2-COOH Pyruvic O=C-COOH carboxylase ATP ADP oxaloacetic Comment of TCA: 1)All reactions are reversible exept (citrate synthetase and α ketoglutanate dehydrogenase) 2)α-ketoglutanate dehydrogenase and succinate dehydrogenase are strictly mitochondrial enzymes. Energy yield in kreb's cycle: NDH 3ATP FAD 2ATP So oxidation of 1 mol of acetyle COA through kreb's produced 12 ATPs as 1ATP from succinyle COA 2ATPs from oxidation of FADH2 of (succinate dehydrogenase) 3ATPs from oxidation of NADH of (α-ketoglutanate dehydrogenase) 3ATPs from oxidation of NADH of (malate dehydrogenase) 3ATPs from oxidation of NADH of(isocitrate dehydrogenase) *Total energy yield in aerobic phase oxidation(kreb's) : (12ATP)+(3ATP)from oxidative decarboxylation =(15ATP) Energy yield from glucose oxidation: Oxidation of one mole of glucose under aerobic condition yield 8ATP in anaerobic phase and 30ATP in aerobic phase of oxidation of 2moles of pyruvic acid obtained from glycolysis. 8 ATP + 30 ATP = 38 ATP