MBMB 451b

Copyright 2000, E.C. Niederhoffer

Sample Problem

Iodoacetic acid inhibits glycolysis by inactivating glyceraldehyde-3-phosphate dehydrogenase. Fructose-1,6-bisphosphate accumulates under these conditions. Why does this metabolite accumulate rather than glyceraldehyde-3-phosphate and dihydroxyacetone phosphate, the products of the reaction immediately preceding glyceraldehyde-3-phosphate dehydrogenase?

Recall that intracellular concentrations of S and P are important in determining DG!

When glyceraldehyde-3-phosphate dehydrogenase is inactivated, glyceraldehyde-3-phosphate would build up but triose phosphate isomerase (DGo' = +7.9 kJ.mol-1) favors dihydroxyacetone phosphate, which in turn would favor fructose-1,6-bisphosphate because the aldolase has DGo' = +22.8 kJ.mol-1. Both triose phosphate isomerase and aldolase are reversible steps.

Fructose-1,6-bisphosphate accumulates because phosphofructokinase-1 is essentially irreversible with DGo' = -17.2 kJ.mol-1.

 

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