Glucose 6-Phosphate Dehydrogenase (G6PD)

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Glucose 6-Phosphate Dehydrogenase(G6PD)

• PDB ID 1QKI
• Yahya Al Hamhoom

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G6PD Discovery

• ? In 1931 German biochemists Warburg and
  Christian discovered G6PD.
• ? They isolated G6PD enzyme from Brewers yeast.
• ? Origin name of G6PD was Zwischenferment
• Zwischen between
• Ferment fermentation

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G6PD Function
? G6PD considered the rate limiting enzyme of the
pentose phosphate pathway. ? It supplies
reducing energy to cells (such as erythrocytes)
by maintaining the level of the NADPH.
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G6PD deficiency

• ? It is an inherited, sex linked metabolic
  disorder caused by mutation in the G6PD gene.
• ? It is the most common enzyme disorder in the
  world
• around 600 million people
• ? Mutations in the gene resulted in the
  production of enzymes with different levels of
  enzymatic activity.
• ? Hemolytic anemia
• Only source for NADPH production in the red blood
  cells

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Structure determination

• ? In 2000 Adams and coworkers determined the
  crystal structure of human G6PD the mutant Canton
  at 3 A resolution.
• ? The most common variant in Chinese population
• contains mutation at position 459 (Arg ? Leu)
• ? The recombinant expression host E coli.

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1-G6PD dimerization

• ? As a homodimer or a homotetramer.
• ? Dimer ? tetramer equilibrium
• Determined by
• 1- pH
• 2- Ionic strength
• ? Individual monomers are inactive.

Identical monomers
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2- Substrate coenzyme binding sites
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3- Coenzyme NADP vs. Structural NADP
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4- The catalytic dyad Mechanism of catalysis