1 / 31

Glycolysis Gluconeogenesis

Glycolysis Gluconeogenesis. One of best characterized pathways Characterized in the first half of 20th century Glucose --> 2 pyruvates + energy Strategy add phosphoryl groups to glucose convert phosphorylated intermediates into compounds with high phosphate group-transfer potentials

urit
Download Presentation

Glycolysis Gluconeogenesis

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Glycolysis Gluconeogenesis

  2. One of best characterized pathways Characterized in the first half of 20th century Glucose --> 2 pyruvates + energy Strategy add phosphoryl groups to glucose convert phosphorylated intermediates into compounds with high phosphate group-transfer potentials couple the subsequent hydrolysis of reactive substances to ATP synthesis Glucose + 2NAD+ + 2 ADP + 2Pi --> 2NADH + 2 pyruvates + 2ATP + 2H2O + 4H+ Glycolysis - Overview

  3. Overview of Glycolysis The Embden-Meyerhof (Warburg) Pathway • Essentially all cells carry out glycolysis • Ten reactions - similar in most cells - but rates differ • Two phases: • First phase converts glucose to two G-3-P • Second phase produces two pyruvates • Products are pyruvate, ATP and NADH • NADH must be recycled • Three possible fates for pyruvate

  4. Glycolysis

  5. Glycolysis

  6. Fate of pyruvate Reduction to lactate Decarboxylation to acetaldehyde Reduction to ethanol Mitochondrial oxidation 1 NADH --> ~3 ATP

  7. Enzymes of glycolysisCatalyzed reactions and properties

  8. Enzymes of glycolysisCatalyzed reactions and properties

  9. Glucose Hexokinase, glucokinase Glucose-6-phosphate Phosphoglucoisomerase Fructose-6-phosphate Phosphofructokinase Fructose-1,6-biphosphate Dihydroxyacetone phosphate Aldolase Glyceraldehyde-3-phosphate Triose phosphate isomerase

  10. First Phase of Glycolysis The first reaction - phosphorylation of glucose • Hexokinase or glucokinase • This is a priming reaction - ATP is consumed here in order to get more later • ATP makes the phosphorylation of glucose spontaneous

  11. Hexokinase1st step in glycolysis; G large, negative • Hexokinase (and glucokinase) act to phosphorylate glucose and keep it in the cell • Km for glucose is 0.1 mM; cell has 4 mM glucose • So hexokinase is normally active! • Glucokinase (Kmglucose = 10 mM) only turns on when cell is rich in glucose • Hexokinase is regulated - allosterically inhibited by (product) glucose-6-P -

  12. Hexokinase • First step in glycolysis • Large negative deltaG • Hexokinase is regulated - allosterically inhibited by (product) glucose-6-P • Corresponding reverse reaction (Gluconeogenesis) is catalyzed by a different enzyme (glucose-6-phosphatase) • Is it the committed step in glycolysis ?

  13. Glucose Glucose-6-P dehydrogenase Glycogen Glucose-6-P Ribose-5-P + NADPH Fructose-6-P Reducing power Nucleic acid synthesis Glyceraldehyde-3-P Pyruvate ATP

  14. Rx 2: Phosphoglucoisomerase Glucose-6-P to Fructose-6-P

  15. Rx 3: Phosphofructokinase PFK is the committed step in glycolysis! • The second priming reaction of glycolysis • Committed step and large, neg delta G - means PFK is highly regulated • ATP inhibits, AMP reverses inhibition • Citrate is also an allosteric inhibitor • Fructose-2,6-bisphosphate is allosteric activator • PFK increases activity when energy status is low • PFK decreases activity when energy status is high

  16. Glycolysis - Second Phase Metabolic energy produces 4 ATP • Net ATP yield for glycolysis is two ATP • Second phase involves two very high energy phosphate intermediates • . • 1,3 BPG • Phosphoenolpyruvate

  17. Glyceraldehyde-3-phosphate Glyceraldehyde-3-phosphate dehydrogenase 1,3-biphosphoglycerate Phosphoglycerate kinase 3-phosphoglycerate Phosphoglycerate mutase 2-phosphoglycerate Enolase phosphoenolpyruvate Pyruvate kinase pyruvate

  18. Rx 10: Pyruvate Kinase PEP to Pyruvate makes ATP • These two ATP (from one glucose) can be viewed as the "payoff" of glycolysis • Large, negative G - regulation! • Allosterically activated by AMP, F-1,6-bisP • Allosterically inhibited by ATP and acetyl-CoA

  19. The Fate of NADH and PyruvateAerobic or anaerobic?? • NADH is energy - two possible fates: • If O2 is available, NADH is re-oxidized in the electron transport pathway, making ATP in oxidative phosphorylation • In anaerobic conditions, NADH is re-oxidized by lactate dehydrogenase (LDH), providing additional NAD+ for more glycolysis

  20. The Fate of NADH and PyAerobic or anaerobic?? • Pyruvate is also energy - two possible fates: • aerobic: citric acid cycle • anaerobic: LDH makes lactate

  21. Energetics of Glycolysis The elegant evidence of regulation! • Standard state G values are scattered: + and - • G in cells is revealing: • Most values near zero • 3 of 10 reactions have large, negative  G • Large negative  G reactions are sites of regulation!

  22. Gluconeogenesis Synthesis of "new glucose" from common metabolites • Humans consume 160 g of glucose per day • 75% of that is in the brain • Body fluids contain only 20 g of glucose • Glycogen stores yield 180-200 g of glucose • So the body must be able to make its own glucose

  23. Comparison of glycolysis and gluconeogenesis pathways

  24. Substrates for Gluconeogenesis Pyruvate, lactate, glycerol, amino acids and all TCA intermediates can be utilized • Fatty acids cannot! • Most fatty acids yield only acetyl-CoA • Acetyl-CoA (through TCA cycle) cannot provide for net synthesis of sugars

  25. Gluconeogenesis I • Occurs mainly in liver and kidneys • Not the mere reversal of glycolysis for 2 reasons: • Energetics must change to make gluconeogenesis favorable (delta G of glycolysis = -74 kJ/mol • Reciprocal regulation must turn one on and the other off - this requires something new!

  26. Energetics of Glycolysis The elegant evidence of regulation! • G in cells is revealing: • Most values near zero • 3 of 10 reactions have large, negative  G • Large negative  G reactions are sites of regulation! • Reactions 1, 3 and 10 should be different to go into opposite direction

  27. Gluconeogenesis II Something Borrowed, Something New • Seven steps of glycolysis are retained: • Steps 2 and 4-9 • Three steps are replaced: • Steps 1, 3, and 10 (the regulated steps!) • The new reactions provide for a spontaneous pathway (G negative in the direction of sugar synthesis), and they provide new mechanisms of regulation

More Related