Phosphoglyceraldehyde dehydrogenase

Until recently much confusion existed as to the precise nature of the oxidation of phosphoglyceraldehyde, and the following steps were commonly cited to explain the sequence of oxidation  

Since phosphate is required in the system, early workers always assumed the formation of an unstable diphosphoglyceraldehyde complex. Because all attempts to isolate this labile complex have failed, it was concluded that a loose physical addition complex was formed. The possible enzymic synthesis of a dimeric form of 1,3-glyceraldehyde-l,3-diphosphate was discounted, since the synthetic compound of this composition was inert in the oxidative system. 

Recently, the work of Racker, Velick, and Harting has done much to reveal the detailed mechanism of the oxidative process. 

For some time it has been known that the sulfhydryl groups of mammalian PGAD had to be maintained in the fully reduced state for enzyme activity. The oxidized form could be readily transformed to the reduced state by exposure to suitable SH reagents such as glutathione and cysteine. The reduced form of the enzyme, having free SH groups, is irreversibly inhibited by low concentrations of iodoacetic acid. Yeast 

PGAD is, however, less sensitive to inhibition by iodoacetic acid and is also less susceptible to inhibition by oxidation. 

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In the two steps catalyzed by 3-phosphoglyceraldehyde dehydrogenase and 3-phosphoglycerate kinase, the oxidation of glyceraldehyde-3-phosphate to glycerate-3-phosphate is coupled to the regeneration of ATP. 

If an uncoupler somehow caused the breakdown of an intermediate form of an electron carrier, the electron carrier would be set free and electron transport to 02 could continue. However, something evidently is different about oxidative phosphorylation compared with the substrate-level phosphorylation catalyzed by 3-phosphoglyceraldehyde dehydrogenase (see chapter 12), because uncouplers have no effect on the latter reaction. Nor do they affect other soluble enzymes that make or use ATP. On the other hand, a molecule that acts as an uncoupler at any one of the three coupling sites of oxidative phosphorylation invariably has a similar effect at the other two sites. This suggests that uncouplers cause the breakdown of something that is generated at all three sites. 

When ammonium salt (48) is allowed to combine with (47) (eq. 21) a complex (47-48 ) having presumably the indicated structure is formed. In this connection one notes also that (48) (as well structurally related ions) is bound to, for example, (49) to which tiyptojrfiane methyl ester units have been attached. This leads to development of a charge-transfer absorption in the complex (49-48 ). That indole-nicotinamidium interactions can provide a charge-transfer absorption is well-known and has been suggested to the responsible for the color of the NAD /3-phosphoglyceraldehyde dehydrogenase complex. ... 

Several enzymes of the Calvin cycle, namely ribu-lose-l,5-bisphosphate carboxylase, fructose bisphos-phatase, 3-phosphoglyceraldehyde dehydrogenase... 

Fig. 1. Pathway of fatty acid synthesis from glucose in animal tissues. The key enzymes or enzyme systems involved are (1) pyruvate dehydrogenase, (2) pyruvate carboxylase, (3) citrate synthase, (4) citrate translocation system, (5) citrate cleavage enzyme, (6) acetyl-CoA carboxylase, (7) fatty acid synthetase, (8) 3-phosphoglyceraldehyde dehydrogenase, (9) malate dehydrogenase, (10) malic enzyme, (11) hexose monophosphate shunt.

Intimate Ion Pair Intermediates in the Solvolysis of Thio Addition Products of NAD(P) Analogs and Their Relevance to the Chemistry of 3-Phosphoglyceraldehyde Dehydrogenase... 

The enzyme 3-phosphoglyceraldehyde dehydrogenase has at the active site an active cysteine (Cys-149) and a histidine residue (His-176). In the presence of the coenzyme NAD" the substrate 3-phosphoglyceraldehyde is oxidized to an acyl phosphate (Eq. (1)). NADH is produced. A thioacylderivative of Cys-149 is first formed and is... 

The reaction catalyzed by aspartic jS-semialdehyde dehydrogenase is analogous to the one catalyzed by 3-phosphoglyceraldehyde dehydrogenase This similarity is shown by the parallel inhibition of both enzymes by iodoacetate and by the catalysis of an arsenolysis of its acyl phosphate substrate by both enzymes. 

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