Hexose monophosphate pathway

Hexose monophosphate pathway

The pentose phosphate pathway is another catabolic reaction pathway like the glycolytic one, that exists in both prokaryotic and eukaryotic cells. Since Hexose monophosphate pathway involves some reactions of the glycolytic pathway, it has been viewed as a"shunt" of glycolysis;therefore it is also called the hexose monophosphate shunt.Its other synonym is the phosphogluconate pathway.

In pentose phosphate pathway Glucose can be oxidized with the release of electron pairs, the released electron may enter the respiratory chain. However, we can not be considered a major energy-yielding pathway in the most microorganism. It provides reducing power in the form of NADPH+H⁺, which is required in many biosynthetic reactions of a cell, and provides pentose phosphates for use in nucleotide synthesis. Although it can produce energy for the cell as an alternate pathway for the oxidation of glucose,it is also a mechanism for obtaining energy from 5-carbon sugars.

The initial phosphorylation of glucose to form glucose-6-phosphate is involved in pentose phosphate pathway, then it is oxidized to 6-phosphogluconic acid with the continuous production of NADPH. Decarboxylation of 6-phosphogluconic acid, together with a production of NADPH, produces ribulose-6-phosphate. Epimerization reactions yield xylulose-5-phosphate and ribose-5-phosphate. These two compounds are the starting point for a series of transketolase reactions and transaldolase reactions leading subsequently to the initial compound of the pathway, 6-phosphogluconic acid,thus completing the cycle.Note that two intermediates of glycolysis fructose-6-phosphate and glyceraldehyde-3-phosphate are generated. Theoretically,by phosphate to CO₂.Specifically,six molecules of glucose-6-phosphate are oxidized to six molecules each of ribulose-5-phosphate and CO₂;five molecules glucose-6-phosphate are then regenerated from the six molecules of ribulose-5-phosphate. The overall equation is as follows:

6Glucose-6-phosphate+12NADP⁺→5glucose-6-phosphate+6CO₂+12NADPH+12H⁺+P_i

In the real situation, it is more probable that the pentose phosphate pathway feeds into the glycolytic pathway by means of fructose-6-phosphate to glyceraldehyde-3-phosphate.

The pentose phosphate pathwayis also called Hexose monophosphate pathway or HMP shunt . For the oxidation of glucose, it is the another pathway to glycolysis and TCA cycle . However, HMP shunt is more anabolic in nature,and it is concerned with the biosynthesis of NADPH and pentose. This pathway starts with glucose 6-phosphate. It is a unique multifunctional pathway since there are several interconvertible substances produced which may proceed in different directions in the metabolic reactions.

Location of the pathway

The enzymes of HMP shunt are located in the cytosol. The tissues such as liver,adipose tissue, adrenal gland,erythrocytes,testes and lactating mammary gland are highly active In HMP shunt.Most of these tissues are involved in the biosynthesis of fatty acids and steroids which depend on the supply of NADPH.

Reactions of the Hexose monophosphate pathway

The sequence of the reaction of HMP pathway is divided into two phase i.e oxidative and non-oxidative.

Oxidative phase: In oxidative phase glucose 6-phosphate dehydrogenase is a the NADP-dependent enzyme that changes the glucose 6-phosphate to 6- phosphogluconolactone. The latter is then hydrolysed by the gluconolactone hydrolase to 6- phosphogluconate. The next reaction involving the synthesis of NADPH is catalyzed by 6-phosphogluconate dehydrogenase to produce 3 keto 6-phosphogluconate which then undergoes decarboxylation to give ribulose 5-phosphate.

G6PD regulates HMP shunt

In this process the first reaction catalyzed by G6PD is most regulatory in HMP shunt. This enzyme catalyzes an irreversible reaction NADPH competitively inhibits G6PD. It is the ratio of NADPH/NAD⁺ that ultimately determines the flux of this cycle.

Non-oxidative phase : The non-oxidative reactions are related with the interconversion of three, four, five and seven carbon monosaccharides. Ribulose 5-phosphate is acted upon by an epimerase to produce xylulose 5-phosphate while ribose 5-phosphate keto isomerizes converts ribulose 5-phosphate to ribose 5-phosphate.

The enzyme transketolase catalysis the transfer of two carbon from xylulose 5-phosphate to ribose 5-phosphate to give a three carbon glyceraldehyde 3-phosphate and a seven carbon sedoheptulose 7-phosphate. Transketolase depends on the coenzyme thiamine pyrophosphate (TTP) and Mg++ ions. Transaldolase brings about the transfer of a three carbon fragment (active dihydroxyacetone) from sedoheptulose 7- phosphate to glyceraldehyde 3-phosphateto give fructose 6-phosphate four carbon erythrose 4-phosphate. transketolase acts on xylulose 5 phosphate and transfers a two-carbon fragment(glyceraldehyde) from it to erythrose 4 phosphate to generate fructose 6 phosphate and glyceraldehyde 3-phosphate.

Fructose 6-phosphate and glyceraldehyde 3-phosphate can be further catabolized through glycolysis and citric acid cycle. Glucose may also be synthesized by these two compounds. For the complete oxidation of glucose 6 phosphates to 6CO₂, we have to start with six molecules of glucose 6 phosphates of these 6,5 moles are regenerated with the production of 12 NADPH. The overall reactions may be represented as

6 glucose 6-phosphate+12 NADP⁺+6 H₂O→6 CO₂+12 NADPH +12 H⁺+5 glucose 6-phosphate

Significance of Hexose monophosphate pathway (HMP)

HMP shunt is different in generating to important products-pentoses and NADPH needed for the biosynthetic reaction and other functions.

Importance of pentoses

In the HMP shunt hexoses are converted into pentoses, the most important being ribose 5 phosphates. The pentose or its derivatives are useful for the synthesis of nucleic acids (RNA and DNA) and many nucleotides such as ATP, NAD⁺, FAD, and CoA. Skeleton muscles are capable of synthesizing pentoses, although only the first few enzymes of HMP shunt are active. Therefore, appears that the complete pathway of HMP shunt may not be required for the synthesis of pentoses.

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References

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Michael J.Pleczar JR, Chan E.C.S. and Noel R. Krieg. Microbiology. Tata Mc GrawHill, 1993.

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Rangaswami and Bagyaraj D.J. Agricultural Microbiology.