MBMB 451b

Copyright 2000, E.C. Niederhoffer

Sample Problem

A cartoon representation of the active sites and the reactions catalyzed by lactate dehydrogenase (LDH) and glyceraldehyde-3-phosphate dehydrogenase (G3PDH) are shown below. Briefly point out a possible role for His195 in LDH and Cys149 in G3PDH in the mechanism of action of these enzymes.

LDH

For LDH, His195 serves as a general base catalyst by removing a H+ from the C2 hydroxyl group of lactate

G3PDH

For G3PDH, Cys149 serves as a nucleophile (S-) to attack the aldehyde (CHO) group of glyceraldehyde-3-phosphate to form a hemithioacetal. This facilitates the hydride transfer to NAD+ and formation of an energy-rich thioester. This is then attacked by the orthophosphate group.

 

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