The Hexose MonoPhosphate Shunt

The Hexose MonoPhosphate Shunt is also known as “Pentose phosphate Pathway” (PPP). This is alternative Glucose oxidation pathway. The hexose monophosphate pathway is used for  production of NADPH from  NADP. The NADPH is required  for  biosynthetic reactions  such  as fatty  acid synthesis, cholesterol  synthesis, drug  reduction, and as a  cofactor for  some  non-synthetic enzymatic reactions. Hexose Monophospahte shunt is the alternative Glucose oxidative pathway.
In addition, it  is used for  the  production of ribose for  nucleotide and nucleic acid synthesis. The hexose monophosphate shunt is also allows the entry  of some carbohydrates  into the glycolytic pathway (especially ribose, but  also some others), and therefore acts as a connection route between different pathways.
Steroidogenic  tissues,  red  blood  cells,  and the  liver  are  the  major sites  of hexose monophosphate  pathway.  Muscle  has  small  amounts  of some of the Hexose MonoPhosphate Shunt enzymes,  because  it  has  little  need for  synthetic  reactions, and therefore,  little  need for  NADPH.
Hexose MonoPhosphate shunt
The muscle, however, like all  tissues, needs to be able to synthesize Ribose  in order to make nucleotides and nucleic acids.

The pentose phosphate pathway (also called “ phosphogluconate pathway” or “Hexose monophosphate Shunt”) occurs in the cytoplasm. It is a source of NADPH and ribose-5-Phosphate for nucleic acid biosynthesis.  It has an oxidative phase (NADPH generation) and a non-oxidative (non-oxidative sugar interconversion).

Phases of Hexose MonoPhaspahate Shunt:

The pentose phosphate pathway occurs in the cytosol and can be divided into two phases:

  • Oxidative phase: it generates NADPH.
  • Non-oxidative phase: synthesize pentose-phosphate and other phosphate monosaccharides.

Oxidative phase:

During oxidative phase, from glucose-6-phosphate obtained by phosphorylation of the free glucose, NADPH finally obtained is formed pentose, ribulose 5-phosphate, why this metabolic process is called “the Pentose Monophosphate Pathway”.

oxidative phase of HMP shunt

  • The first reaction is the oxidation of glucose 6-phosphate, carried out by the enzyme glucose-6-phosphate dehydrogenase. In this first step the C1 group is dehydrogenated to give a group carboxyl, which, next to C5 forms a lactone, i.e. an ester intramolecular.
  • It is here that two free hydrogen ions (proton) and two electrons are transferred to NADP+ which acts as electron acceptor being reduced to form the first molecule of NADPH; the remaining proton is released in the middle.
  • Then, the produced hydrolysis of the lactone by the action of the lactonase, whereby the free acid is obtained 6-phosphogluconate.
  • Then, the latter becomes ribulose 5-phosphate by the action of 6-phosphogluconate dehydrogenase.
  • Here NADPH second molecule is obtained, in addition to the release of a molecule of CO 2 because of the oxidative decarboxylation.
  • Finally, the enzyme pentose-5-phosphate isomerase, by an intermediary enediol, isomerizes the ribulose 5-phosphate and converts ribose-5-phosphate to the transformation of the group ketose in aldose.
  • This latter reaction prepares a central component nucleotide synthesis for the biosynthesis of RNA, DNA and nucleotide cofactors. At the same time, it carries out the transition to non-oxidative metabolic phase of the pentose phosphate pathway.

It ends thus obtaining two NADPH molecules which, besides their use in reductive biosynthesis, is also responsible for maintaining a reducing environment within the cell. This can be seen if there is a deficit of glucose-6-phosphate dehydrogenase, produced by a defect in a gene located on the X chromosome, which may affect more proportion to men.

Non-oxidative phase:

The non-oxidative phase of the pentose phosphate pathway is initiated when the cell needs more NADPH than ribose-5-phosphate. In this second process are a complex sequence of reactions that let you change the C3, C4, C5, C6 and C7 pentose sugars to form finally glyceraldehyde-3-phosphate and fructose 6-phosphate, which can go directly to glycolysis.

non oxidative phase of HMP shunt

  • This phase includes a series of reversible reactions, the direction of which depends on the availability of substrate. Also the isomerization of ribulose-5-phosphate to ribose-5-phosphate is also reversible.
  • This enables us to eliminate excess ribose-5-phosphate to finish transforming it into intermediates of glycolysis.
  • The first reaction is carried out epimerization, regulated by the pentose-5-phosphate epimerase enzyme, which converts the ribulose-5-phosphate, a product of the oxidative phase, xylulose-5-phosphate, thereby generating the necessary substrate for controlled by the following reaction transketolase, which acts together with coenzyme thiamine pyrophosphate (TPP).
  • This will convert xylulose 5-phosphate into ribose-5-phosphate and, by transferring unit C2 of the aldose to ketose, will produce glyceraldehyde-3-phosphate and sedoheptulose-7-phosphate.
  • Finally the transaldolase , with the help of a rest lysine in the active site, transfers a unit C3 sedoheptulose-7-phosphate to glyceraldehyde-3-phosphate, which will form the tetrose erythrose-4-phosphate, in addition of one of the first end products: fructose 6-phosphate, which is directed towards glycolysis.

Then, again transketolase enzyme transferring a C2 unit, from xylulose-5-phosphate to erythrose-4-phosphate, thus form another molecule of fructose 6-phosphate and glyceraldehyde-3-phosphate, both intermediaries glycolysis. Thus, the phase of this non-oxidative metabolic pathway is closed.

Overall Pathway:

This stage of the route will connect the metabolic processes that generate NADPH with originating NADH/ATP. Furthermore, glyceraldehyde-3-phosphate and fructose 6-phosphate may be involved instead of the glycolysis, in gluconeogenesis to form a new glucose synthesis.

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