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For HMP Pathway -Lecture-1

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Non Oxidative phase (Reversible phase of HMP pathway)

The pentose phosphate pathway (hexose monophosphate shunt) is a more complex pathway than glycolysis.It is presumed that three molecules of glucose-6-P enter simultaneously to give rise to three molecules of CO2 and three five-carbon sugars. These are rearranged to regenerate two molecules of glucose 6-phosphate and one molecule of the glycolytic intermediate, glyceraldehyde– 3 -phosphate (Figure–1).

Reactions of HMP pathway

Figure-1- 3 molecules of Glucose-6-P enter simultaneously in this pathway to produce 3 molecules of CO2, 6 NADPH, 2 fructose-6-P and one molecule of glyceraldehyde-3-P. 2 molecules of Fructose-6-P are converted to 2 molecules of Glucose-6-P while  Glyceraldehyde-3-P is presumed to be equivalent to half a molecule of Glucose-6-P. Three carbons less are presumed to be lost as CO2. If 6 molecules enter at the same time, then it would represent loss of 6 molecules of CO2 equivalent to complete oxidation of one molecule of glucose.

Details of reactions

Step-1- The reaction is catalyzed by Transketolase (Figure-1 and 2)

The net reaction is-

 Reaction of Transketolase

Transketolase catalyzes the transfer of the two-carbon unit comprising carbons 1 and 2 of a ketose (from Xylulose 5-phosphate) to the aldehyde carbon of an aldose sugar (Ribose 5-phosphate), producing the seven-carbon ketose sedoheptulose 7-phosphate and the aldose glyceraldehyde 3-phosphate. It therefore effects the conversion of a ketose sugar into an aldose with two carbons less and an aldose sugar into a ketose with two carbons more (Figure-2). The reaction requires Mg2+ and thiamine pyrophosphate (vitamin B1) as coenzyme. The two-carbon moiety transferred is probably glycoaldehyde bound to thiamine pyrophosphate.


Figure-2- Two phosphorylated pentoses (Keto and aldo pentoses) rearrange by transfer of two carbon units from Keto pentose (Xylulose-5-P) to Aldopentose (Ribose-5-P) to form phosphorylated aldo triose (Glycerladehyde-3-P) and phosphorylated keto heptose (Sedoheptulose-7-P). The reaction is reversible and is catalyzed by TPPTransketolase dependent enzyme.

Clinical significance- R.B.C Transketolase activity is measured to diagnose underlying thiamine deficiency, since the enzyme is TPP dependent. In thiamine deficiency Transketolase activity is reduced.

Step- 2- The reaction is catalyzed by Transaldolase enzyme (Figure-1 and 3)

The net reaction is represented as follows-

 Reaction of Transaldolase

Transaldolase catalyzes the transfer of a three-carbon Dihydroxyacetone moiety (carbons 1–3) from the ketose sedoheptulose -7-phosphate onto the aldose glyceraldehyde 3-phosphate to form the ketose fructose 6-phosphate and the four-carbon aldose Erythrose 4-phosphate. (Figure-3)


Figure 3-  Transaldolase catalyzed reaction involves the rearrangement of Phosphorylated trio aldose (Glyceraldehyde-3-P) and keto heptose (Sedoheptulose-7-P) by shifting of 3 carbon units to form keto hexose (Fructose-6-P) and aldo tetrose (Erythrose-4-P).

Step-3- The reaction is catalyzed by Transketolase enzyme (Figure-1 and 4)



In this reaction catalyzed by transketolase, Xylulose 5-phosphate again serves as a donor of glycoaldehyde. In this case Erythrose 4-phosphate is the acceptor, and the products of the reaction are fructose 6-phosphate and glyceraldehyde 3-phosphate. (Figure 4)



Figure-4- Transketolase catalyzes the interconversion of  phosphorylated aldotetrose (C4) and ketopentose( C5) to form glycolytic intermediates , fructose-6-P (C6 ) and glyceraldehyde-3-P (C3).

Since the reactions of non oxidative phase are irreversible, the glycolytic intermediates can also rearrange to form pentoses.

The sum of these reactions is

 Net reaction of non oxidative phase

Xylulose 5-phosphate can be formed from ribose 5-phosphate by the sequential action of phosphopentose isomerase and phosphopentose Epimerase, and so the net reaction starting from ribose 5-phosphate is-

 Conversion of ribose-5-P to glycolytic intermediates

Thus, excess ribose 5-phosphate formed by the pentose phosphate pathway can be completely converted into glycolytic intermediates. Moreover, any ribose ingested in the diet can be processed into glycolytic intermediates by this pathway.

It is evident that the carbon skeletons of sugars can be extensively rearranged to meet physiologic needs.

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