Harpers

GLYCOLYSIS & THE OXIDATION OF PYRUVATE / 139S EnzH C OH C OHH C OHNAD +H C OHCH 2 O PCH 2 O PGlyceraldehyde 3-phosphateEnzyme-substrate complexHS EnzNAD +OCOPBoundcoenzymeSubstrateoxidationby boundNAD +H C OHCH 2 O P1,3-BisphosphoglyceratePiSEnzSEnzHC OC OHCH 2 OC ONADH + H +H C OHNADH + H + NAD +CH 2 O PNAD * +*PEnergy-rich intermediateFigure 17–3. Mechanism of oxidation of glyceraldehyde 3-phosphate. (Enz, glyceraldehyde-3-phosphatedehydrogenase.) The enzyme is inhibited by the ⎯SH poisoniodoacetate, which is thus able to inhibit glycolysis. The NADH produced on the enzymeis not as firmly bound to the enzyme as is NAD + . Consequently, NADH is easily displacedby another molecule of NAD + .undergo the reverse reaction. The pyruvate kinase reactionis thus also irreversible under physiologic conditions.The redox state of the tissue now determines whichof two pathways is followed. Under anaerobic conditions,the reoxidation of NADH through the respiratorychain to oxygen is prevented. Pyruvate is reducedby the NADH to lactate, the reaction being catalyzedby lactate dehydrogenase. Several tissue-specific isoenzymesof this enzyme have been described and haveclinical significance (Chapter 7). The reoxidation ofNADH via lactate formation allows glycolysis to proceedin the absence of oxygen by regenerating sufficientNAD + for another cycle of the reaction catalyzed byglyceraldehyde-3-phosphate dehydrogenase. Under aerobicconditions, pyruvate is taken up into mitochondriaand after conversion to acetyl-CoA is oxidized toCO 2 by the citric acid cycle. The reducing equivalentsfrom the NADH + H + formed in glycolysis are takenup into mitochondria for oxidation via one of the twoshuttles described in Chapter 12.Tissues That Function Under HypoxicCircumstances Tend to Produce Lactate(Figure 17–2)This is true of skeletal muscle, particularly the whitefibers, where the rate of work output—and thereforethe need for ATP formation—may exceed the rate atwhich oxygen can be taken up and utilized. Glycolysisin erythrocytes, even under aerobic conditions, alwaysterminates in lactate, because the subsequent reactionsof pyruvate are mitochondrial, and erythrocytes lackmitochondria. Other tissues that normally derive muchof their energy from glycolysis and produce lactate includebrain, gastrointestinal tract, renal medulla, retina,and skin. The liver, kidneys, and heart usually take up