438 2. ANALOGS OF ENZYME REACTION COMPONENTS 



and the mercapto fatty acids, where the a-OH is replaced by an a-SH 

 group, are particularly interesting and deserve further study to determine 

 their specificity on lactate metabolism. 



The oxidation of glycolate is catalyzed by glycolate oxidase and the 



CHO-CHO- + NADH + H+ ;fi CH^OH-COO- + NAD+ 

 Glyoxylate Glycolate 



reverse reaction by glyoxylate reductase, both enzymes being found in 

 plants. This reaction is similar to the pyruvate ±5 lactate interconversion 

 and, indeed, L-lactate is slowly oxidized by the oxidase. Since these enzymes 

 bear some relationship to those involved in lactate metabolism due to this 

 similarity, it is not inappropriate to discuss them at this point, particularly 

 as Zelitch at the Connecticut Agricultural Experiment Station has reported 

 some very interesting inhibitions by analogs. Glyoxylate reductase is ap- 

 parently not especially susceptible to analogs: the following inhibitions were 

 observed with 16.5 mM glyoxylate and 10 mM analogs — phenylglyoxy- 

 late 21%, oxalacetate 22%, oxamate 31%, and pyruvate 56% (Zelitch, 

 1955). Glycolate oxidase, on the other hand, is well inhibited by a-hydrox- 

 ysulfonates. Competitive inhibition was found with hydroxymethanesul- 

 fonate {K, = 0.0018 mM), a-hydroxyethanesulfonate (^,; = 0.0023 mM), 

 and sulfoglycolate {K^ = 0.0021 mM); since K,,^ = 0.38 mM, these analogs 

 are reasonably potent (Zelitch, 1957). Rabbit muscle lactate dehydrogenase 

 is inhibited comparably, D-glycerate dehydrogenase less strongly, and ma- 

 late dehydrogenase not at all, so that some specificity toward enzymes 

 oxidizing a-hydroxy acids is evident. The inhibition of lactate oxidation 

 by the glycolate oxidase is inhibited very strongly because lactate is bound 

 less tightly to the enzyme. Another competitive inhibitor of comparable 

 potency is of-hydroxy-2-pyridinemethanesulfonate (Zelitch, 1959) which 

 has been used in most of the in vivo work apparently because it is more 

 effective in cells, although sulfoglycolate w^ould seem to act very similarly 

 (Zelitch, 1958). 



OH 



I 



CH3— CH— SO3 H0-CH2— so; 



Q-Hydroxyethanesulfonate HydroxymethanesuKonate 



9" ^N OH 



I /^ \ I 



'OOC — CH-SO; \\ A>— CH-SO3 



Sulfoglycolate ■^^'^^^!'u''^'K . 



pyridinemethanesulfonate 



