Glyceraldehyde 3-phosphate dehydrogenase
- OMIM: 138400
- UniProt: P04406
- MGI: 3646088
The glyceraldehyde -3-phosphate dehydrogenase ( GAPDH ) is an enzyme of glycolysis and therefore essential for all living things. It catalyzes the conversion of glyceraldehyde-3- phosphate to 1,3- bisphosphoglycerate. In this reaction, a high energy phosphate bond is built up which is transmitted in the following step of the glycolysis of ADP, ATP is produced thereby. Further, a NAD to NADH / H is converted in the catalyzed reaction.
The catalytic mechanism
The main problem of the reaction, the elimination of H - ion ( hydride ) of the aldehyde group of glyceraldehyde-3- phosphate dar. This is energetically unfavorable, since the carbon carrying a positive charge in the aldehyde. By the covalent binding of a sulfhydryl group of a cysteine of the enzyme a nucleophilic residue is introduced. This will solve the hydride ion and between enzyme and substrate results in a thioester. These energy -rich compound is used in the subsequent reaction to bind an inorganic phosphate, and convert the intermediate product into the 1,3- bisphosphoglycerate. The hydride now binds to a non- covalently bound NAD so that NADH / H formed. This is released from the binding with the enzyme and is replaced by a NAD in order to restore the original state.
The catalyzed reaction takes energy a high priority. The resulting mixed anhydride of phosphoric acid and carboxylic acid is used in the subsequent reaction for ATP formation. From the NADH / H ATP in turn can be formed in the respiratory chain.
Inhibition
The formation of energy-rich anhydride is inhibited by arsenic. AsO43 - binds analogously to the phosphate to the GAPDH. NADH is further formed .. The bond between the carboxylate, which is formed from the oxidation of the aldehyde and the arsenate is very unstable, so that the mixed anhydride is divided into 3- phosphoglycerate. Characterized a energiefixierender step in glycolysis is skipped, which contributes to the toxicity of arsenic.