Glycolysis

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Glycolysis
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Glycolysis

• Represents the second phase of catabolism of
  carbohydrates.
• The sequence of reactions that converts glucose
  to pyruvic acid.
• However, there may be other end-products,
  especially when O2 is absent or limiting
• e.g. Lactate in exercising muscle
• Ethanol in yeast

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• Total oxidation of glucose so as to obtain
  maximal energy would be
• C6H12O6 6 O2 6 CO2 6 H2O
• This is the overall process that occurs in cells-
  glycolysis is the first part of it
• C6H12O6 2 Pyruvic acid
• Cytoplasmic. The pyruvic acid is subsequently
  converted to acetyl CoA and then to CO2.

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Plan to Glycolysis

• (1) All the carbon intermediates are either
  six-carbon units or three-carbon units
• (2) The 6-C units (glucose) is phosphorylated to
  a hexose-bis-phosphate (energy utilizing)
• (3) This hexose-bis-phosphate is cleaved to 2
  molecules of triose phosphate
• (4) These triosephosphates are converted to
  pyruvate with the liberation of energy.

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• i.e.
• Hexose Hexose-bis-phosphate
• Hexose-bis-phosphate 2
  TriosePhosphate
• 2 TriosePhosphate 2 Pyruvic Acid

3 Steps
1 Step
6 Steps
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Metabolic Pathway
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First Reaction

• Glucose Glucose-6-phosphate
• Irreversible
• This reaction is an example of a phosphoryl
  transfer i.e. a phosphoryl group from ATP is
  transferred to the hydroxyl group on C-6 of
  glucose.
• It is catalyzed by an enzyme known as HEXOKINASE.

Mg 2
ATP
ADP H
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• Mg 2 is a required cofactor- as it is for all
  kinases (ATP requiring enzymes).
• Infact ATP is not the true substrate but rather
  an ATP-Mg2 chelate. An ADP-Mg2 chelate is the
  true product.
• Another enzyme GLUCOKINASE is capable of carrying
  out this reaction.
• Found in only in liver and in ß cells of pancreas
  
• hexokinase and glucokinase perform the same
  function in glycolysis.

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Second Reaction

• Reversible
• Catalyzed by phosphohexose isomerase
• Isomerization reaction as can be seen from the
  open-chain formula.

Aldose
Ketose
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Third reaction

• Irreversible
• Catalyzed by phosphofructokinase (PFK)
• A critical regulatory enzyme in determining the
  overall rate of glycolysis
• Another phosphoryl transfer from ATP to the
  hydroxyl on carbon-1 of F-6-P.
• Again Mg 2 is a required cofactor- ATP Mg2 is
  the actual substrate.

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• Aldolase catalyzes an aldol cleavage
• (opposite of an aldol condensation)
• Reversible

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• Reversible
• Isomerization

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• Reversible
• Oxidation-reduction reaction

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• NAD - Nicotinamide Adenine Dinucleotide
• Biological OXIDIZING agent
• NADH Biological REDUCING agent

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• The aldehyde at C-1 is converted to an Acyl
  Phosphate- a mixed anhydride of phosphoric and
  carboxylic acid
• This has the effect of generating a high energy
  phosphate bond which will be harvested to form ATP

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• Reversible
• Phosphoryltransfer
• The high energy phosphate is transferred to
  ADP to produce ATP

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• Reversible
• Intramolecular shift of the phosphor group

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• Reversible
• The phosphoenolpyruvate now contains a
  high-energy phosphate bond
• Why?

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• Irreversible
• Phosphoryl transfer
• Requires Mg2
• The high energy phosphate of PEP is is
  transferred to ADP to form ATP
• Why??

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