432 2. ANALOGS OF ENZYME REACTION COMPONENTS 



dialysis. It was considered that the true inhibitors are the aldehydes cor- 

 responding to the keto acids, and it was shown that COg is evolved from 

 phenylpyruvate and p-hydroxyphenylpyruvate but not from the other 

 three inhibitors. Although this does not completely invalidate the aldehyde 

 proposal, it makes it unlikely. On the other hand, it is possible that the 

 tight complex is formed with some intermediate prior to decarboxylation. 

 Hydroxypyruvate is decarboxylated by yeast decarboxylase at a rate 

 1/76 that of pyruvate and strongly inhibits the pyruvate reaction (Holzer 

 et al., 1955 d). It was thought that hydroxypyruvate might exert some 

 regulatory function on pyruvate metabolism in yeast. Formaldehyde and 

 acetaldehyde inhibit pyruvate decarboxylase but the mechanism may not 

 be competitive with substrate (Bauchop and Dawes, 1959). The oxidation 

 of pyruvate in rat kidney slices is inhibited around 70% by 20 mM meso- 

 tartrate, but not at all by d- and DL-tartrates (after correction for the inhi- 

 bition of endogenous respiration) (Quastel and Scholefield, 1955). This 

 inhibition is completely reversed by fumarate and malate. However, when 

 mitochondria were examined it was found that there is little direct effect on 

 pyruvate oxidation but a rather strong inhibition of or-ketoglutarate oxida- 

 tion, which is progressive with time. In the presence of bicarbonate, pyru- 

 vate is oxidized and this is inhibited by meso-tartrate. It was assumed 

 that the inhibition is upon the incorporation of CO.2, and it was stated that 

 meso-tartrate is a specific inhibitor of pyruvate oxidation in slices of rat 

 kidney cortex, a conclusion that would seem to be unjustified since so few 

 systems were tested. 



LACTATE METABOLISM 



A specific inhibitor of lactate dehydrogenase would be useful in studying 

 the effects of a block of glycolytic lactate formation and for determining 

 the role of this enzyme in the functioning of tissues. One of the most in- 

 teresting lactate dehydrogenase inhibitors is oxamate, first reported by 

 Hakala et al. (1953), who stated that it is the most potent inhibitor of many 

 lactate and pyruvate analogs examined. The inhibition is competitive with 



O 



+H3N— C— coo- 



Oxamate 



respect to pyruvate,* noncompetitive with respect to lactate and NAD, 

 and uncompetitive with respect to NADH (Papaconstantinou and Colo- 



* Examination of the double reciprocal plot reveals that the situation is not purely 

 competitive but mainly so. 



