Question

is it more energetically expensive to feed monosaccharides other than glucose into the glycolytic pathway? explain.

why is the cell's ability to regenerate NAD+ critical to glycolysis? which glycolytic enzyme requires NAD+?

Answer 1

Ans. #1. No, feeding non-glucose monosaccharides in glycolytic pathways need NOT necessarily energetically more expensive.

Note the following points-

I. In normal glycolytic pathways, glucose is converted to fructose-6-phosphate (F-6-P) on expenditure of 1 ATP, which is committed to go further in glycolysis.

II. Fructose also directly to glycolysis when it’s converted to F-1-P on expenditure of 1 ATP. F-1-P is catalyzed by fructose-1-phosphate aldolase into glyceraldehyde-3-P and dihydroxyacetone phosphate without requiring any ATP consumption.

So, entry of fructose in glycolytic pathway also consumes 1 ATP – equal to ATP consumed by glucose for its conversion into F-6-P.

Therefore, entry of fructose into glycolytic pathway is NOT energetically more expensive than the entry of glucose.

#III. The enzyme hexokinase phosphorylates hexoses. For example, hexose converts mannose into mannose-6-phosphate (M-6-P) on expenditure of 1 ATP. M-6-P is further isomerized into F-6-P by phosphomannose isomerase without any ATP consumption. The resultant F-6-P acts as glycolytic intermediate as usual. C

Therefore, entry of mannose into glycolytic pathway is NOT energetically more expensive than the entry of glucose.

Conclusion: Entry of monosaccharides at any point of glycolysis is most likely NOT to exceed the ATP consumption for conversion of glucose into phosphorylated forms in preparatory phase. Therefore, the energetics of entry of a monosaccharide into glycolysis is most likely to be equal to that of normal preparatory phase till the respective point of entry into glycolytic pathway.

#2. Glycraldehyde-3-phosphate dehydrogenase required NAD⁺ as its cofactor. NAD⁺ acts as electron acceptor in the reaction catalyze by the enzyme.

As cofactors are crucial for the activity of their respective enzyme, unavailability of NAD⁺ would lead to loss of catalytic activity of the enzyme. Inhibition Glycraldehyde-3-phosphate dehydrogenase would further lead to inhibition of the whole glycolytic pathways in feedback loop.

# Therefore, for glycolysis to continue, the cell must be able to regenerate NAD⁺ - be it be ETC or by fermentation pathway.