ARGINASE 337 



interaction energies from the constants given are shown in the following 

 tabulation. Two types of inhibition may be possible: (1) competitive inhi- 

 bition by diamino compounds that are probably oriented as the substrate, 

 and (2) partially competitive or noncompetitive inhibition by monoamines 



^ . ., . Relative — Ji^ of binding 



Inhibitor ,, ,, , , 



(kcal/mole) 



L-Ornithine 3.82 



L-Lysine 3 . 72 



L-Norvaline 2 . 53 



L-Isoleucine 2 . 48 



L- Valine 1.98 



L-Cysteine 1 . 94 



L-Leucine 1.81 



L-a-AminobutjTate 1.40 



L-Phenylalanine 1 . 09 



L-Xorleucine . 87 



L-Proline 0.78 



L- Aspartate . 67 



L- Alanine 0.61 



L-Citrulline 0.47 



L-Serine 0.25 



L-Tryptophan 0.21 



L-Histidine -0.82 



Glycine —0.99 



that may be oriented otherwise. Inhibitory activity increases in the straight- 

 chain series from glycine to norvaline; each additional methylene group 

 contributes 1.17 kcal/mole to the binding energy, a value similar to that 

 found in other series, and undoubtedly due to dispersion forces. It is odd 

 that there is a sudden and marked drop in the affinity on adding another 

 methylene group to form norleucine. As pointed out by Hunter and Downs, 

 it is difficult to establish structural correlation in the series of substituted 

 alanines (shown in the accompanying table); why, for example, is cysteine 

 bound so much more tightly than serine? Substitution in the a-amino group 

 (carbamyl or formyl) always reduces the activity; hence this probably con- 

 stitutes one binding group. The experiments were done at pH 8.4 and 

 therefore all carboxyl groups were essentially completely ionized, but there 

 would be some variation between the inhibitors with respect to the fraction 

 of the amino groups protonated {pK^'s for these inhibitors run from 8.2 

 to 10.6). 



