Serylmethionine

Dipeptidase activity in homogenate from small intestinal mucosa is determined according to the method of Josefsson (1965) in 45 patients with chronic non-specific enteritis. The majority of the enzymes are of the endopeptidase group, degrading the dipeptides of the neural aminoacids; glycyl-alanine, alanyl-l-valine, glycyl-l-isoleucine, analyl-glycine, leucyl-l-leucine, alanyl-l-leucine, alanyl-l-proline, glycyl-l-glutamic acid; only one enzyme-glycyl-l-leucine dipeptidase belongs to the enzymes of the brush-like zone of the enterocyte. The glycyl-l-alanine dipeptidase enzyme activity was established to be decreased with 49,2 per cent, glycyl-l-leucine--with 33,2 per cent, glycyl-l-valine with 19,6 per cent, glycyl-l-isoleucine--with 61 per cent, etc. The diminished enzyme activity corresponds, in the majority of the cases, to the severity of the disease and to the degree of the histological changes. It does not reach the decreased degree, found in the patients with coliac sprue. In a series of cases the enzymatic activity does not correspond to the morphological changes: "normal activity" and decreased peptidase activity were found in six cases and in two cases--"partial mucosal atrophy" and normal or elevated peptidase activity. Very likely, the pointed out enzymes, are of a substantial importance for the pathogenetic digestive and resorbtive disturbances in chronic non-specific enteritis, especially protein disturbances.

The effects of variation in dietary protein content on small intestinal brush border and cytosol peptide hydrolase activities have been investigated. One group of rats was fed a high protein diet (55% casein) and another group was fed a low protein diet (10% casein). After 1 wk, brush border peptide hydrolase activity (L-leucyl-beta-naphthylamide as substrate) and cytosol peptide hydrolase activity (L-prolyl-L-leucine as substrate) were determined in mucosae taken from the proximal, middle, and distal small intestine. As judged by several parameters, brush border peptide hydrolase activity was significantly greater in rats fed the high protein diet when data for corresponding segments were compared. In contrast, no significant difference was seen in cytosol peptide hydrolase activity. IN A SECOND STUDY, BRUSH BORDER AND CYTOSOL PEPTIDE HYDROLASE ACTIVITIES WERE DETERMINED IN THE PROXIMAL INTESTINE BY UTILIZING AN ADDITIONAL THREE PEPTIDE SUBSTRATES: L-leucyl-L-alanine, L-phenylalanylglycine, and glycyl-L-phenylalanine. Sucrase, maltase, and alkaline phosphatase activities were also determined. As before, brush border peptide hydrolase activities were significantly greater in rats fed the high protein diet. However, activities of the nonproteolytic brush border enzymes did not vary significantly with diet. In contrast to the results obtained with L-prolyl-L-leucine as substrate for the cytosol enzymes, cytosol activity against the three additional peptide substrates was greater in rats fed the high protein diet. It is suggested that the brush border peptide hydrolase response to variation in dietary protein content represents a functional adaptation analogous to the regulation of intestinal disaccharidases by dietary carbohydrates. The implication of the differential responses of the cytosol peptide hydrolases is uncertain, since little is known of the functional role of these nonorgan-specific enzymes.

Both corticosterone and T4 have been previously implicated as causal factors in the ontogenic increases in jejunal sucrase and maltase activities during the third week of life in the rat. Furthermore, it is known that the administration of exogenous T4 during the developmental period causes significant increases in serum corticosterone concentrations. To determine whether the effects of T4 on sucrase and maltase are secondary to the corticosterone rise, we examined the effect of T4 administration in adrenalectomized (adX) pups. Serum corticosterone was measured in all operated animals. Some of the adX pups had substantial concentrations of circulating corticosterone. In adX pups with serum corticosterone levels below 0.1 microgram/dl, there was no effect of T4 on either maltase or sucrase activity. We also studied the effect of propylthiouracil-induced hypothyroidism on sucrase and maltase. At 21 days of age, both enzyme activities were significantly reduced in hypothyroid pups. Injections of either T4 or cortisone acetate were equally effective in restoring activities to normal. For sucrase, there was no further increase in activity when both hormones were administered. For maltase, the combined treatment gave activities that were significantly higher than those with either hormone alone. We conclude that for both sucrase and maltase, the effects of changes in thyroid status are primarily due to the accompanying changes in serum corticosterone. The normal rate of development of both enzymes appears to be principally under glucocorticoid control, although for maltase, T4 may have a facilitory action.