The absorption of the keto acid analogues of the branched chain amino acids from rat shall intestine

Abstract

THE ABSORPTION OF THE KETO ACID ANALOGLIES OF THE BRANCHED CHAIN AMINO ACIDS FROM RAT SMALL INTESTINE, F. L. Weber, Jr., and S. Desk*, V.A. Hospital and the University of Kentucky School of Medicine, Lexington, Kentucky. The keto acid analogues (KAA's) of essential amino acids, given orally, are promising agents in the treatment of uremia, portal systemic encephslopathy, and urea cycle enzyme deficiencies. They provide a source of essential amino acids which contain no nitrogen. But, little is known about the mechanism of KAA intestinal absorption. The mechanism of absorption of the KM of valine (K-val) was compared to the corresponding amino acid valine (val) by perfusing rat jejunum and ileum in viva. Keto acids -were determined spectrophotometrically or by gas-liquid chromatography. In both ileum and jejunum K-val was absorbed at rates only moderately below those of the amino acid valwhen perfused at l-50 mM. In the jejunum, absorption rates for K-val relative to val ranged from 7339% at perfusate concentrations of 1 and 25 mM respective1Y. Similar results were obtained in the ileum. There was a plateauing in K-val absorption rates at higher perfusate concentrations suggesting saturable transport. In further studies, 3 ml+! K-vsl was perfused into jejunal segments. Twenty-five mM of the KAA's of isoleucine and phenylslanine (structural analogues of K-val), inhibited K-val absorption by 43 and 50% respectively while 3 mM of the KAA of isoleucine did not. Sixty-seven mu val and 56 mM glucose significantly increased K-val absorption by 30 and 57% respectively, while there were corresponding kfold and f&fold increments in water transport. The KAA's of leucine and isoleucine were absorbed at the ssme rates as K-val when perfused at 3 and 25 mM. Arterial and mesenteric venous blood was sampled after perfusing 25 mM of the branched chain KAA's. There was a significant release of the corresponding amino acids into mesenteric venous blood compared to controls suggesting partial transamination during absorption. The data indicate: (1) K-val absorption is in part mediated through a saturable mechanism, distinct from the val carrier. (2) K-val absorption is influenced by solvent drag. (3) Partial transsmination occurs during KAA absorption.