ANALOGS WHICH ARE ISOMERS OF SUBSTRATES 269 



However, the primary purpose of this section is to discuss instances in 

 which significant inhibition by optical isomers is observed. 



The asparaginase of Mycobacterium phlei attacks only L-asparagine and 

 this deamidation is quite well inhibited by D-asparagine (Grossowicz and 

 Halpern, 1956 a). It is a particularly clear and straightforward instance 

 of stereomeric inhibition and a 1/v — 1/(S) plot shows it to be completely 

 competitive. Ai'ound 75% inhibition is produced by 40 mM D-asparagine 

 when L-asparagine is 10 mM. On the other hand, the asparaginases of 

 Bacillus coagulans and B. stearothermophilus are inhibited by D-asparagine 

 but not competitively (Manning and Campbell, 1957). The type of inhi- 

 bition is difficult to designate since the double reciprocal plots intersect 

 to the right of the ordinate, that is, the inhibition does not tend toward 

 noncompetitive kinetics. A yet more complex situation is presented in the 

 depression of the formation of a-amylase by D-aspartate in Pseudomonas 

 saccharophila, 0.2 mM blocking the protein synthesis completely (Eisen- 

 stadt et a]., 1959). The inhibition is readily reversed by L-aspartate and is 

 characterized by a fairly long lag period before inhibition is observed. 

 The inhibition was assvimed to be on the reaction: 



L- Aspartate + IMP + GTP -> fumarate + AMP + GDP + P 



thus producing an impairment in AMP synthesis, this secondarily disturbing 

 the formation of ATP and the activation of amino acids for protein synthesis. 

 Examination of this reaction in cell-free extracts showed that D-aspartate 

 does indeed inhibit competitively. Another type of inhibition is exhibited 

 by pea glutamine synthetase with L-glutamate, ammonia, and ATP as 

 substrates (Varner, 1960). D-Glutamate inhibits the formation of L-gluta- 

 mine. However, D-glutamate is also a substrate and actually has a lower 

 K„^ although the reaction rate is slower than with L-glutamate (^,„ for 

 L-glutamate is 10 mM and for D-glutamate is 2 mM). This is then an exam- 

 ple of a competitive inhibition between isomeric substrates. It may also 

 be mentioned that D-glutamate inhibits, although quite weakly, the de- 

 carboxylation of L-glutamate by bacterial glutamate decarboxylase (Ro- 

 berts, 1953). 



The splitting of L-histidine by rat liver histidase is inhibited by D-histi- 

 dine, 11% inhibition being given by 2 mM, 36% by 12 mM, 55% by 24 

 mM, and 85% by 48 mM when the L-histidine is 12 mM (Edlbacher et al., 

 1940). The formation of L-histidine from L-histidinol occurs in two steps: 



L-Histidinol -^ L-histidinal -> L-liistidine 



The enzymes catalyzing both these reactions are inhibited by D-histidinol 

 and D-histidinal competitively (Adams, 1955). The Ki for D-histidinol is 

 0.05 mM for both oxidations by a yeast preparation and it is possible that 

 only a single enzyme is involved. 



