Hexose Monophosphate Pathway or Pentose Phosphate Pathway (With Animation)


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Introduction:

Breakdown of carbohydrates (glucose) takes place in the body by glycolysis followed by tricarboxylic acid cycle (Kreb’s cycle) resulting in yield of energy in the form of ATP. Glucose can alternatively also undergo a different pathway to produce other products required by the cells. One of these alternate pathway is the pentose phosphate pathway or also called as hexose monophosphate pathway in which oxidation of glucose 6-phosphate takes place to produce pentoses. The fate of glucose whether to undergo glycolysis or the hexose monophosphate pathway is decided by the relative concentrations of NADP+ and NADPH. Hexose monophosphate shunt is useful in adipose tissue, liver, erythrocytes, testes, adrenal glands and lactating mammary glands.

Hexose Monophosphate Pathway Reactions

This metabolic pathway is fragmented into two phases taking place in the cytosol as all the enzymes required are present there: the oxidative and the non-oxidative phase which are described below with the help of an animation. Click the play button to progress.

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Discussion

Oxidative phase of Hexose Monophosphate Shunt

Oxidative phase of Hexose Monophosphate Shunt

 

Oxidative Phase:

  • This phase starts with the oxidation of  glucose 6-phosphate by the enzyme glucose 6-phosphate dehydrogenase to yield 6-phosphoglucono-δ-lactone. This enzyme is an NADP dependent enzyme, where NADP+accepts an electron to form NADPH + H+.
  • The product 6-phosphoglucono-δ-lactone then gets hydrolyzed to 6-phosphogluconate by a specific enzyme lactonase
  • The product obtained from the previous reaction i.e 6-phosphogluconate gets decarboxylated and oxidized to give D-ribulose 5-phosphate and also NADPH + H+ is produced once more. This reaction was catalyzed by the enzyme 6-phosphogluconate dehydrogenase.
  • The final step of the oxidative phase is the conversion of ribulose 5-phosphate to its isomer ribose 5-phosphate by the enzyme phosphopentose isomerase.

This is the end of HMP pathway for many tissues (read below- the use of pentose sugars for the fate of ribose 5-phosphate), while in the others the pathway continues towards the non-oxidative phase. NADPH and ribose 5-phosphate are the end products formed in this phase which play their respective roles further.

Non-Oxidative Phase:

Non- Oxidative phase of Hexose Monophosphate Shunt

Non- Oxidative phase of Hexose Monophosphate Shunt

  • This phase continues with the isomerisation of ribulose 5-phosphate to xylulose 5-phosphate by the enzyme epimerase and at the same time ribulose 5-phosphate is also converted to ribose 5-phosphate by the enzyme 5-phosphate ketoisomerase.
  • In the next step, 7 carbon moiety sedoheptulose 7-phosphate and 3 carbon compound glyceraldehyde 3-phosphate is formed by the transfer of 2 carbon moiety from xylulose 5-phosphate to ribose 5-phosphate in the presence of the enzyme transketolase. The transketolase enzyme requires coenzyme thiamine pyrophosphate (TPP) and Mg2+ ions.
  • Now, in the presence of the enzyme transaldolase, a 3 carbon fragment is transferred from sedoheptulose 7-phosphate to glyceraldehyde 3-phosphate to give fructose 6-phosphate (6c) and erythrose 4-phosphate (4C).
  • Once again, the enzyme transketo