Pentose phosphate pathway (PPP) or hexose monophosphate (HMP) shunt




Pentose phosphate pathway (PPP) or Hexose mono-phosphate (HMP) shunt

• Pentose phosphate pathway is an alternative pathway to glycolysis and TCA cycle for oxidation of glucose.
• It is a shunt of glycolysis
• It is also known as hexose monophosphate (HMP) shunt or phosphogluconate pathway.
• It occurs in cytoplasm of both prokaryotes and eukaryotes
• Pentose phosphate pathway starts with glucose and it is a multi-steps reaction.


• The sequence of reactions are divided into two types.

I) oxidative reaction phase
II) Non-oxidative reaction phase

 

Oxidative phase:

  • First four reactions are irreversible and oxidative in which glucose molecule is oxidized twice generating two molecules of NADPH and glucose is converted into Ribose-5 phosphate.

1st reaction: conversion of glucose to glucose-6 phosphate.

  • This reaction is catalyzed by the enzyme hexokinase and a molecule of ATP is utilized. This reaction is actually a primary step of glycolysis.

2nd reaction: conversion of glucose-6 phosphate to 6-phosphogluconolactone.

  • This reaction is catalyzed by an enzyme glucose-6 phosphate dehydrogenase (G6PD) in the presence of Mg++ ion.
  • In this reaction a molecule of NADPH is produced.

3rd reaction: conversion of 6-phosphogluconolactone to 6-phosphogluconate

  • This reaction is a hydrolysis reaction catalyzed by hydrolase enzyme

4th reaction: conversion of 6-phosphogluconate to ribose-5 phosphate

  • This reaction is catalyzed by the enzyme 6-phosphogluconate dehydrogenase to produce 3-keto-6-phosphogluconate which undergoes decarboxylation to produce ribulose-5 phosphate.
  • In this reaction a molecule of NADPH is generated.

 

Non oxidative phase:

  • Oxidative reactions is followed by a series reversible sugar phosphate inter-conversion reaction.
  • Ribulose-5-phosphate is epimerized to produce xylulose 5-phosphate in the presence of enzyme phosphor pentose epimerase. Similarly ribulose-5-phosphate is also keto-isomerized into ribose 5-phosphate.
  • Xylulose-5-phsphate transfer two carbon moiety to ribose 5-phospahate in the presence of enzyme transketolase to form sedoheptulose-7-phosphate and glyceraldehyde 3—phosphate.
  • Sedoheptulose -7-phosphate transfer three carbon moiety to glyceraldehyde -3-phosphate to form fructose 6-phopsphate and erythrose 4-phosphate in the presence of enzyme transaldolase.
  • Transketolase enzyme catalyse the transfer of two carbon moiety from Xylulose-5-phsphate to erythrose-4- phosphate to form fructose-6-phosphate and glyceraldehyde-3-phosphate.
  • Fructose-6-phosphate and glyceraldehyde-3-phosphate is later enter into glycolysis and kreb’s cycle.
  • The rate and direction of reversible reaction depends upon the needs of cell.
  • If cell needs only NADPH then fructose-phosphate and glyceraldehyde-3-phosphate are converted back to glucose by reverse glycolysis, otherwise converted to pyruvate and enter TCA cycle generating ATPs.

Significance of Pentose phosphate pathway

  • HMP is only the cytoplasmic pathway that generates NADPH
  • NADPH is produced in this pathway acts as reducing agent during biosynthesis of various molecules eg. fattyacids.
  • This pathway generates 3, 4, 5, 6 and 7 carbon compounds which are precursors for biosynthesis of other molecules. Eg nucleotides are synthesized from ribose-5-phsophate.
  •  Pentose phosphate pathway is very essential for cell lacking mitochondria (eg.RBCs) for generation of NADPH.
  • Triose, tetrose, pentose, hexose and heptose sugar are generated as intermediate products in pentose phosphate pathway.
  • NADPH is also used to reduce (detoxify) Hydrogen peroxide in cell.
  • Resistance to malaria in some Africans are associated with deficiency of glucose-6-phosphate dehydrogenase enzyme because malarial parasites depend upon HMP shunt to reduce glutathione in RBCs.

Pentose phosphate pathway (PPP) or hexose monophosphate (HMP) shunt