1. To investigate the kinetics of ophidian l-amino acid oxidase, V and K(m) were determined for phenylalanines that were substituted in every ring position with groups of various size and reactivity, and for a few ring-substituted tryptophans and histidines. The venom of one representative from each of three major classes of poisonous snakes, Naja melanoleuca, Vipera russelli and Crotalus adamanteus, served as a source of the ophidian l-amino acid oxidase. Both crude and crystalline enzyme from the venom of C. adamanteus were tested. 2. The introduction of a benzene ring into glycine and alanine caused some increase of V and a very marked depression of K(m). 3. With the exception of fluorine, residues in the ortho position of phenylalanine led to a decrease of V. The rates induced by various substitutions follow the pattern: meta >/= para >/= ortho. Within the halogen series, the effects become more pronounced with increasing atomic number. 4. Ring substitution in heterocyclic amino acids also affected the V values markedly. For methyl-substituted tryptophans the pattern was: 5-methyl >/= 6-methyl >/= 4-methyl. In a few instances ring substitution accounts for a considerable elevation of V, as shown for beta-quinol-4-ylalanine and its 6-methoxy derivative. 5. The kinetic constants appear to be unaffected by relatively high concentrations of the corresponding d-amino acids. 6. A general principle that permits a uniform interpretation of a vast body of information is suggested. It is based on the assumption that most substrates form not only eutopic but also dystopic complexes with the enzyme. The latter, in contrast with the former, do not permit the formation of reaction products. K values for eutopic and dystopic complexes are computed. Similar concepts have been presented to elucidate the action of alpha-chymotrypsin (Hein & Niemann, 1962) and of monoamine oxidase.

Summary. The transfer of intravenously injected enzymes from blood to Thiry- Vella fistulas of the small intestine was studied in dogs. The enzymes used were highly purified preparations of glutamic-pyruvic transaminase and two glutamicoxalacetic transaminases. The rate of transfer varied greatly, depending on whether isotonic or hypertonic solutions were placed inside the loop. On the other hand, there was relatively little difference in the transfer of the three enzymes, although their plasma-disappearance half-fives varied from 2.6 days to less than 1 hour. Quantitative estimates indicate that this pathway, which appears to represent nonspecific transudation across the intestinal mucosa, contributes relatively little to the metabolic clearance of the three enzymes, in contrast to the clearance of a serum protein. Zymosan, which had been found earlier to inhibit the metabolic clearance of enzymes apparently because of its blocking effect on the reticuloendothelial system, was without effect on the intestinal clearance of the enzymes. A slower but significant transfer of enzyme was also noted in the direction of intestine to blood.

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