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GLYCOLYSIS Glycolysis: oxidative breakdown of glucose to pyruvate with capture of some energy as ATP, NADH (first step in respiration) Glycolysis glucose pyruvate Subsequent reactions lactate (or) CO2+ethanol (or) O2 absent malate CO2 + H2O -- O2 present Glycolysis can be divided into two phases: priming and payoff Phase 1: five priming reactions 1. glucose + ATP G-6-P + ADP 2. G-6-P F-6-P 3. F-6-P + ATP F-1,6-bisP + ADP 4. F-1,6,bisP DHAP + G-3-P 5. DHAP G-3-P Glycolysis can be divided into two phases: priming and payoff Phase 2: five payoff reactions 6. G-3-P + PI + NAD+ 1,3-bisPGA + NADH 7. 1,3-bisPGA + ADP 3-PGA + ATP 8. 3-PGA 2-PGA 9. 2-PGA PEP 10. PEP + ADP pyruvate + ATP Reaction 6 DGo’ =+6.3 kJ/mol DG’ = -1.29 kJ/mol Near equilibrium: not regulated Note that the C in -C-O-PO3 has been oxidized (from aldehyde to acid) The coupling of acyl-phosphate formation to oxidation avoids an energy hump that would drastically slow the reaction. Summary of glycolysis: glucose + 2 ADP + 2 Pi + 2 NAD + 2 pyruvate + 2 ATP + 2 H2O + 2 NADH + 2 H+ What happens next? It depends on the environment: aerobic or anaerobic. Regeneration of NAD + is essential to keep the process going. including oxidation of NADH In fungi and plants in the absence of O2, pyruvate is decarboxylated to acetaldehyde; acetaldehyde is reduced to ethanol; NADH is oxidized to NAD+. The NAD+ is recycled to oxidize more glyceraldehyde-3-P. In animals and some bacteria, pyruvate is reduced to lactate as NADH is oxidized to NAD+. Control: activity of glycolysis depends on allosteric enzymes and responds to energy requirement. In muscle: Control: activity of glycolysis depends on allosteric enzymes and responds to energy requirement. In liver, fructose-2,6-bisP is a important stimulator of PFK: enhances substrate activation relieves allosteric inhibition Cancer cells produce most of their ATP by glycolysis (Warburg effect) Why do proliferating cells switch to a less efficient metabolism? Probable answer: growth requires more Ccompounds and reduction power (NADPH), than ATP energy. (see Science 324:1029 May 22, 2009) Summary •Glucose is metabolized to pyruvate in a series of 10 reactions. •Glycolysis provides the cell (cytoplasm) with 2 mol ATP/glucose. •Glycolysis also provides cytoplasm with 2 mol NADH/glucose. •In the absence of O2, NADH is oxidized by reduction of pyruvate. •In the presence of O2, NADH is oxidized in the mitochondria. •Rate of glycolysis is controlled at 3 key allosteric enzymes.