268 2. ANALOGS OF ENZYME REACTION COMPONENTS 



The examples chosen to ilhistrate transport inhibition do not always 

 involve analogs, except in the most general sense, but clearly demonstrate 

 the importance of considering such a type of interference whenever analogs 

 are used in cellular preparations. 



ANALOGS WHICH ARE ISOMERS OF SUBSTRATES 



The behavior of the isomers of normal metabolites, particularly optical 

 isomers, constitutes, in a way, a special field and therefore some of the more 

 interesting results will be discussed in this section rather than under the 

 specific enzymes that are involved. The concept that a proper fit of a sub- 

 strate to the enzyme surface is necessary for reaction implies that enzymes 

 will usually be stereospecific, and this has been demonstrated many times. 

 Since an enzyme commonly attacks only one form of an isomeric pair, 

 the unreactive form may be either an inhibitor or completely inert. In most 

 cases the unreactive form does not bind to the enzyme at all, as might be 

 expected from the different spatial configurations of most isomeric pairs, 

 and is not inhibitory. 



Enantiomeric Analogs 



These analogs are related to the corresponding substrates on the basis 

 of molecular asymmetry and the most common examples are optically 

 active due to an asymmetric carbon atom. Unnatural enantiomers often 

 exhibit no affinity for the enzymes. Indeed, it has been generally found 

 that D-amino acids do not interfere with the microbial growth-promoting 

 activity of L-amino acids, although there are exceptions. Some examples 

 of a lack of inhibition by optical isomers may be mentioned. The oxidation 

 of L-phenylalanine by the L-amino acid oxidase of Neurospora is not in- 

 hibited by D-phenylalanine, even when the latter is present at 500 times 

 the concentration of the substrate (Burton, 1951 b), and D-tryptophan 

 does not inhibit E. coli L-tryptophanase even though it interferes with 

 growth (Gooder and Happold, 1954). D-Malate is not oxidized by the malate 

 dehydrogenase of Mycobacterium tuberculosis nor does it inhibit the oxida- 

 tion of L-malate (Goldman, 1956 b). A rather unusual case is presented by 

 potato tyrosinase in that both l- and D-tyrosine are attacked at the same 

 rate, but there is no evidence of mutual inhibition, perhaps because of the 

 limited range of concentrations used (Spencer et al., 1956). Occasionally 

 a slight inhibition is noted but one which would not be of any practical 

 significance, as in the just detectable inhibition by D-leucine of the oxida- 

 tion of L-leucine by the L-amino acid oxidase of the hepatopancreas of 

 Cardium tuberculatum, an inhibition actually much less than exerted by 

 other amino acids and hence probably not specific (Roche et al., 1959). 



