Fates of Lactate, Pyruvate and NADH PDF

Fates of Lactate, Pyruvate and NADH Feeder Pathways of Glycolysis: Metabolism of Monosaccarides and Disaccarides Fates of Pyruvate 1. Oxidative pyruvate decarboxylation of 2. Carboxylation of pyruvate to oxaloacetate 3. Reduction of pyruvate to ethanol (microorganisms) Ethanol Fermentation Fates of...

Fates of Lactate, Pyruvate and NADH Feeder Pathways of Glycolysis: Metabolism of Monosaccarides and Disaccarides Fates of Pyruvate 1. Oxidative pyruvate decarboxylation of 2. Carboxylation of pyruvate to oxaloacetate 3. Reduction of pyruvate to ethanol (microorganisms) Ethanol Fermentation Fates of Pyruvate under Anaerobic Conditions: Fermentation Lactic Acid Fermentation Regenerates NAD+ for further glycolysis under anaerobic conditions Lactic acid fermentation The reaction takes place in a variety of microorganisms and in the cells of higher organisms when the amount of oxygen is limiting, as in muscle cells during intense activity. Reduction of pyruvate to lactate, reversible During strenuous exercise, lactate builds up in the muscle – Generally less than 1 minute The acidification of muscle prevents its continuous strenuous work NAD+ is Regenerated from the Metabolism of Pyruvate Under aerobic conditions: Pyruvate is oxidized to acetate, which enters the citric acid cycle. Under Hypoxic/ unaerobic conditions: NAD is regenerated by lactate or ethanol fermentation TISSUES DEPENDENT ON ANAEROBIC GLYCOLYSIS Tissues, rely on anaerobic glycolysis; including; – red blood cells – the kidney medulla – the tissues of the eye In tissues with mitochondria, both aerobic and anaerobic glycolysis occur simultaneously. – The relative proportion of the two pathways depends on the mitochondrial oxidative capacity of the tissue and its oxygen supply FATE OF LACTATE Lactate released from cells undergoing anaerobic glycolysis is taken up by other tissues (primarily the liver, heart, and skeletal muscle) and oxidized back to pyruvate. In the liver, the pyruvate is used to synthesize glucose, which is returned to the blood. In many other tissues, lactate is oxidized to pyruvate, which is then oxidized to CO2 in the TCA cycle. The Cori Cycle Metabolic cooperation between skeletal muscle and the liver (glucose → lactate → glucose) The lactate can be transported to the liver and converted to glucose there - High amount of oxygen consumption to fuel gluconeogenesis - Restores muscle glycogen stores OTHER FUNCTIONS OF GLYCOLYSIS SHUTTLES INVOLVED IN GLYCOLYSIS Inner mitochondrial membrane is impermeable to NADH and no transport protein exists that can directly translocate NADH across this membrane. 1. Glycerol 3-phosphate shuttle 2. Malate–aspartate shuttle Glycerol 3-phosphate shuttle The major shuttle in most tissues – Important in skeletal muscle and brain The glycolytic intermediate dihydroxyacetone phosphate can be converted to glycerol-3-phosphate by glycerol-3- phosphate dehydrogenase; this process also results in conversion of NADH to NAD. Glycerol 3-phosphate then diffuses through the outer mitochondrial membrane to the inner mitochondrial membrane, where the electrons are donated to a membrane-bound flavin adenive dinucleotide (FAD)containing glycerophosphate dehydrogenase. Malate–aspartate shuttle NADH produced by glycolysis reduces oxaloacetate (OAA) to malate, which crosses the mitochondrial membrane and is reoxidized to OAA. Important in liver, heart, kidney Cytoplasmic NADH oxidized using the malate shuttle produces a mitochondrial NADH and yields approximately 3 ATP (or 2.5 ATP) by oxidative phosphorylation. Cytoplasmic NADH oxidized by the glycerol phosphate shuttle produces a mitochondrial FADH2 and yields approximately 2 (or 1.5 ATP) ATP by oxidative phosphorylation. Feeder Pathways for Glycolysis Glucose molecules are cleaved from glycogen and starch by glycogen phosphorylase – Yielding glucose-1-phosphate Disaccharides are hydrolyzed – Lactose: glucose and galactose – Sucrose: glucose and fructose – Fructose, galactose, and mannose glycolysis at different points enter Feeder Pathways for Glycolysis Entry of dietary glycogen, starch, disaccharides, and hexoses into the preparatory stage of glycolysis