- Glycolysis – Glucose Catabolic Pathway
- Citric acid cycle : Central metabolic cycle and its Significance
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:
Table of Contents
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.
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”.
- 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.
The general reaction of this first phase is:
Glucose-6-phosphate + 2 NADP + + H 2 O
→ ribulose-5-phophate + 2 NADPH + 2 H + + CO 2
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.
- 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.
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.