Glycolysis

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Glycolysis
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The Fate of Pyruvate
1. Aerobic conditions oxidized to acetyl CoA
which enters the citric acid cycle for further
oxidation 2. Anaerobic conditions
(microorganisms) conversion to ethanol 3.
Anaerobic conditions (muscles, red blood cells)
conversion to lactate
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Fig. 8.8
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Glycolytic pathway (other sugars)

• Monosaccharides
• Galactose (converted to glucose-6-phosphate)
• Fructose (phosphorylated to FBP)
• Mannose (isomerization to F6P)
• Disaccharides
• Maltose (glucose)
• Lactose (galactose and glucose)
• Sucrose (fructose and glucose)

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Regulation of Glycolysis

• When ATP is needed, Glycolysis is activate
• When ATP levels are sufficient, glycolysis
  activity decreases

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Fig. 8.11
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The Pentose Phosphate Pathway

• The primary role
• Generation of NADPH for reductive biosynthesis
• Produce 5 carbon sugars for nucleotide and
  nucleic acid biosynthesis

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Introduction

• Predominant pathway for glucose catabolism is
  Glycolysis
• PPP is Primarily anabolic rather than catabolic
• Comprises two phases
• Oxidative phase
• Non oxidative phase

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Oxidative Phase

• Involves three reactions
• Two oxidations produce NADPH
• Enzymes
• G6P dehydrogenase (Oxidation to Lactone)
• Lactonase (Hydrolysis)
• 6-Phosphogluconate dehydrogenase (Oxidative
  decarboxylation))

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Oxidative Phase Summary

• Net results of Oxidative Phase
• Generation of 2 NADPH
• Oxidation of 1-C (lost) to CO2
• Synthesis of 1 mole of Ribulose-5-phosphate
  (pentose phosphate)

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Non Oxidative Phase

• Ribulose-5-phosphate from oxidative phase has two
  fates
• Epimerization to Xylulose-5-phosphate
• Ribulose-5-phosphate 3-epimerase
• Isomerization to Ribose-5-phosphate
• Ribose-5-phosphate isomerase

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• Small amount of ribose-5-phosphate required for
  nucleotide synthesis
• Remainder of 5-C sugars into glycolytic
  intermediates
• Key glycolytic intermediates G3P and F6P

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Transketolase and Transaldolase

• Catalyze transfer of 2-C and 3-C fragments
  respectively
• Transketolase transfers an aldol moiety
  (glycoaldehyde)
• Transaldolase transfers a ketol moiety
  (dihydroxyacetone)

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Transketolase and Transaldolase

• Catalyze transfer of 2-C and 3-C fragments
  respectively
• Transketolase transfers an aldol moiety
  (glycoaldehyde)
• Transaldolase transfers a ketol moiety
  (dihydroxyacetone)

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Summary

• Depending on cell needs for Ribose-5-phosphate,
  NADPH and ATP
• Pentose Phosphate Pathway can operate in 3 major
  scenarios
• Ribulose-5-phoshate to ribose-5-phosphate
• G3P and F6P converted to G6P re-enter PPP
• G3P and F6P may enter Glycolysis

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Citric acid cycle
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Conversion of Pyruvate to acetyl-CoA

• Catalyzed by pyruvate dehydrogenase complex and
  coenzymes (PDC)
• Loss of pyruvate carboxyl group
• Activation of remaining 2 C unit
• Generation of CO2
• Generation of NADH
• Formation of Acetyl-CoA

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Pyruvate dehydrogenase complex

• Multi-enzyme assembly
• Pyruvate dehydrogenase (E1)
• Dihydrolipoamide acetyl-transferase (E2)
• Dihydrolipoamide dehydrogenase (E3)

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Coenzymes

• Thiamine pyrophosphate (TPP)
• Used for a-ketoacid decarboxylation
• Lipoic acid (lipoamide)
• Internal disulfide, attached covalently to lysine
• Flavin adenine dinucleotide (FAD)
• Electron acceptor
• NAD
• Coenzyme A( CoA)
• Acyl carrier

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Coenzyme A (hydrolysis)

• Less resonance stabilization (larger atomic size
  for S compared to O)
• Thioester is destabilized relative to ester
• ?G of hydrolysis is higher for thioester
• Acyl group is more readily transferred to other
  metabolites (as in Citric acid cycle)

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Thioester hydrolysis
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Citric acid Cycle

• Also known as Tricarboxylic acid or Krebs cycle
• Centre for energy production from sugar, fat and
  protein
• Proceeds in two phases
• Formation of citrate (Oxaloacetate acetyl-CoA)
  Citrate synthase
• Regeneration of Oxaloacetate

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