HMP Shunt | Anatomy2Medicine
HMP Shunt Pathway

HMP Shunt

  • Reactions of the pentose phosphate pathway
  • Oxidative reactions
    • Glucose 6-phosphate is converted to 6-phosphogluconolactone
      • NADP+ is reduced to NADPH + H+.
      • Enzyme glucose 6-phosphate dehydrogenase,
    • 6-Phosphogluconolactone is hydrolyzed to 6-phosphogluconate
      • Enzyme gluconolactonase.
    • 6-Phosphogluconate is oxidatively decarboxylated
      • CO2 is released, and a second NADPH + H+ is generated from NADP+.
      • The remaining carbons form ribulose 5-phosphate.
      • Enzyme involved is 6-phosphogluconate dehydrogenase.
  • Non oxidative reactions
    • Ribulose 5-phosphate is isomerized to ribose 5-phosphate or epimerized to xylulose 5-phosphate.
    • Ribose 5-phosphate and xylulose 5 – phosphate undergo reactions , catalyzed by transketolase and transaldolase, that transfer carbon units, ultimately forming fructose 6-phosphate and glyceraldehyde 3-phosphate.
    • Trans ketolase, which requires thiamine pyrophosphate, transfers two-carbon units
    • Trans aldolase transfers three-carbon units.
    • Overall reactions of the pentose phosphate pathway
      • 3 glucose−6−P 6 NADP→3 ribulose−5−P 3 CO2 6 NADPH
      • 3 ribulose−5−P→2 xylulose−5−P + ribose−5−P

 

  • 2 xylulose−5−P ribose−5−P →2 fructose−6−P glyceraldehyde−3−P

 

    • Functions of NADPH
      • The pentose phosphate pathway produces NADPH for fatty acid synthesis. Under these conditions, the fructose 6-phosphate and glyceraldehyde 3-phosphate generated in the pathway reenter glycolysis.
      • NADPH is also used to reduce glutathione (-glutamylcysteinylglycine).
      • Glutathione helps to prevent oxidative damage to cells by reducing hydrogen peroxide (H2O2).
      • Glutathione is also used to transport amino acids across the membranes of certain cells by the -glutamyl cycle.
    • Generation of ribose 5-phosphate
      • When NADPH levels are low, the oxidative reactions of the pathway can be used to generate ribose 5-phosphate for nucleotide biosynthesis.

 

  • When NADPH levels are high, the reversible nonoxidative portion of the pathway can be used to generate ribose 5-phosphate for nucleotide biosynthesis from fructose 6-phosphate and glyceraldehyde 3-phosphate.

 

  • A deficiency of glucose 6-phosphate dehydrogenase
    • causes insufficient amounts of NADPH to be produced
    • when strong oxidizing agents, such as some antimalarial drugs, are present, NADPH is needed for maintaining  reduced glutathione.
    • As a result, glutathione is not adequately reduced and, in turn, is not available to reduce compounds that are produced by the metabolism of these drugs and to protect membranes from oxidative damage.
    • Red blood cells lyse, and a hemolytic anemia can occur.