Chapter 14 Glycolysis Gluconeogenesis and the Pentose Phosphate Pathway by storing glucose as a high molecular weight polymer such as starch or glycogen the cell can stockpile large quantities of hexose units while maintaining a relatively low cytosolic osmolarity glucose can also supply a huge array of metabolic intermediates for biosynthetic reactions in animals and vascular plants glucose has four major fates o it may be used in the synthesis of complex polysaccharides destined for the extracellular space o stored in cells o oxidized to a three carbon compound via glycolysis to provide ATP and metabolic intermediates o oxidized via the pentose phosphate pathway to yield ribose 5 phosphate for nucleic acid synthesis and NADPH for reductive biosynthetic processes Organisms that do not have access to glucose have to make it o Photosynthetic organisms make it by reducing atmospheric CO2 to trioses then converting the trioses to glucose o Nonpohotosynthetic cells make glucose from simpler three and four carbon precursors by gluconeogenesis reversing glycolysis 14 1 Glycolysis glycolysis catalyzed reactions to yield two molecules of the three carbon compound pyruvate the splitting of a molecule of glucose in a series of enzyme o Some of the free energy released during these steps is conserved as ATP and NADH The glycolytic breakdown of glucose is the sole source of metabolic energy in some mammalian tissues and cell types o Some plants that are modified to store starch and some aquatic plants derive most of their energy from glycolysis o Many anaerobic microorganisms are completely dependent on glycolysis Fermentation other organic nutrients to obtain energy conserved as ATP a general term for the anaerobic degradation of glucose or o Probably most ancient biological mechanism for obtaining energy from organic fuel molecules An Overview Glycolysis Has Two Phases There are 10 steps total the first 5 of which constitute the preparatory phase The first 5 steps o ATP first phosphorylates glucose at the hydroxyl group on C 6 o The D glucose 6 phosphate thus formed is converted to D fructose 6 phosphate o The D fructose 6 phosphate is phosphorylated by ATP at C 1 to yield D fructose 1 6 bisphosphate o Fructose 1 6 bisphosphate is split to yield two three carbon molecules dihidroxyacetone phosphate and glyceraldehyde 3 phosphate o Dihydroxyacetone phosphate is isomerized to a second molecule of glyceraldehyde 3 phosphate In the preparatory phase the energy of ATP is invested raising the free energy content of the intermediates and the carbon chains of all the metabolized hexoses are converted to glyceraldehyde 3 phosphate The energy gain comes in the payoff phase of glycolysis 5 steps of payoff phase o Each molecule of glyceraldehyde 3 phosphate is oxidized and phosphorylated by inorganic phosphate to form 1 3 bisphosphoglycerate o Energy is released as two molecules of 1 3 bisphosphoglycerate are converted to two molecules of pyruvate steps 7 10 The net yield is two molecules of ATP and 2 NADH per molecule of glucose In the sequential reactions of glycolysis three chemical transformations are noteworthy o Degradation of the carbon skeleton of glucose to yield pyruvate o Phosphorylation of ADP to ATP by compounds with high phosphoryl group transfer potential formed during glycolysis o Transfer of hydride ion to NAD forming NADH Fates of Pyruvate o The pyruvate that is formed during glycolysis is further metabolized via one of three catabolic routes In aerobicorganisms or tissues under aerobic conditions pyruvate is oxidized with loss of its carboxyl group as CO2 to yield the acetyl group of acetyl coenzyme A The acetyl group is oxidized completely to CO2 by the citric acid cycle The electrons from these oxidations are passed to O2 through a chain of carriers in mitochondria to form H2O The energy from the electron transfer reactions drives the synthesis of ATP in mitochondria Pyruvate is reduced to lactate via lactic acid fermentation When vigorously contracting skeletal muscle must function under low oxygen conditions hypoxia In some plant tissues and in certain invertebrates protists and microorganisms pyruvate is converted under hypoxic or anaerobic conditions to ethanol and CO2 ethanol alcohol fermentation o Pyruvate can also be anabolized Can provide carbon skeleton for the synthesis of alanine or fatty acids ATP and NADH Formation Coupled to Glycolysis Energy Remaining in Pyruvate o Glycolysis only releases a small fraction of the total available energy Pyruvate contains most of the chemical potential energy of Importance of Phosphorylated Intermediates o Phosphoryl groups have three functions from glucose glucose cell The phosphorylated glycolytic intermediates cannot leave the Phosphoryl groups are essential components in the enzymatic conservation of metabolic energy Binding energy resulting from the binding of phosphate groups to the active sites of enzymes lowers the activation energy and increases specificity of the enzymatic reactions The Preparatory Phase of Glycolysis Requires ATP Step 1 Phosphorylation of Glucose o Glucose is activated for subsequent reactions by its phosphorylation at C 6 to yield glucose 6 phosphate with ATP as the phosphoryl donor Irreversible Catalyzed by hexokinase o Hexokinase requires Mg2 for its activity Mg2 shields the negative charges of the phosphoryl groups in ATP making the terminal phosphorus atom an easier target for nucleophilic attack by an OH of glucose o Hexokinase undergoes a profound change in shape an induced fit when it binds glucose Brings bound ATP closer to a molecule of glucose also bound to the enzyme and blocks the access of water o Hexokinase is a soluble cytosolic protein and is present in nearly all organisms o Isozymes are encoded by different genes two or more enzymes that catalyze the same reaction but Step 2 Conversion of Glucose 6 Phosphate to Fructose 6 Phosphate o Phosphohexose isomerase phosphoglucose isomerase the enzyme that catalyzes the reversible isomerization of glucose 6 phosphate an aldose to fructose 6 phosphate a ketose o The isomerization proceeds readily in either direction Step 3 Phosphorylation of Fructose 6 Phosphate to Fructose 1 6 Bisphosphate the enzyme that catalyzes the transfer of a phosphoryl group from ATP to fructose 6 phosphate o Phosphofructokinase 1 PFK 1 Forms fructose 1 6 bisphosphate o The reaction is essentially irreversible under cellular conditions o Some bacteria and protists and