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Chapter 13. Chem 341 Suroviec Fall 2013. I. Overview. Glycolysis co n verts to two C 3 units. The free energy released in this process is harvested to synthesize ATP from ADP and P i. I. Overview. Some pathways are irreversible. Catabolic and anabolic pathways MUST differ.
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Chapter 13 Chem 341 Suroviec Fall 2013
I. Overview • Glycolysis converts to two C3 units. The free energy released in this process is harvested to synthesize ATP from ADP and Pi
I. Overview • Some pathways are irreversible • Catabolic and anabolic pathways MUST differ C. Every metabolic pathway has a 1st committed step
II. Glucose A. Glucose • 6 carbon sugar with aldehyde group • form: OH group of the anomeric C is on OPPOSITE side of ring from CH2OH • form: OH group of the anomeric C is on SAME side of ring from CH2OH
II. Glucose C. Glycogenolysis • Only liver can make glucose available to the liver at large
III. Glycolysis • Stage I. Energy investment • Glucose is phosphorylated and cleaved • Uses 2 ATP • Stage II. Energy recovery • 2 molecules of glyceraldehyde-3-phosphate converted to pyruvate • Produces 4 ATP
Hexokinase Metabolically irreversible reaction IV. Reactions of Glycolysis
Conversion of G6P to F6P B. Phosphoglucose Isomerase
PFK phosphorylates FBP Operates similar to hexokinase C. Phosphofrutokinase • Tetrameric enzyme • R and T states in equilibrium • ATP is both a substrate and and allosteric inhibitor
Each PFK has 2 binding site Substrate site Inhibitor site Inhibitor site binds ATP only in T state Shifts equilibrium in favor of T at high ATP concentrations C. PFK
Catalyzes cleavage of FBP to form GAP and DHAP D. Aldolase
GAP continues down the glycolytic pathway DHAP and GAP are ketose-aldose isomers Final reaction Stage I E. Triose Phosphate Isomerase
Exergonic reaction Synthesis of high energy 1,3-BPG F. Glyceraldehyde-3-Phosphate Dehydrogenase
G. Phosphoglycerate Kinase • Bilobal with Mg2+ • 1,3-BPG common intermediate whose consumption pulls reaction forward
3PG is converted to 2PG Phosphorylated His is needed to complete reaction 2,3-BPG allosteric inhibitor of deoxyhemoglobin H. Phosphoglycerate Mutase
2PG dehydrated to PEP Needs Mg2+ F- inhibitor of reaction I. Enolase
PEP is cleaved via PK to form pyruvate Forms ATP Step 1: ADP nucleophilically attacks the PEP, forms ATP Step 2: Enolpyruvate tautomerizes to pyruvate J. Pyruvate Kinase
ATP Investment of 2 ATP per glucose Generation of 4 ATP NADH Glucose oxidized 2 NAD+ reduced to NADH Electron transport Pyruvate 2 molecules are produced Complete oxidation to CO2 done in citric acid cycle 3 products of glycolysis
Pyruvate Aerobic conditions completely oxidized to CO2 and H2O Anaerobic conditions converted to reduced end product to reoxidize NADH III. Fermentation
Demand for ATP high Supply of oxygen is low A. Homolactic Fermentation
Forms CO2, ethanol and NAD+ TPP is essential cofactor of pyruvate decarboxylase B. Alcoholic Fermentation
Glycolysis operates continuously in most tissues Flux must vary to meet needs How do we determine to flux control mechanisms? IV. Control of Glycolysis • One 3 reactions of glycolysis potentially control it: • Hexokinase • Phosphofrucokinase • Pyrivate kinase