Biomedical Sciences ETDs

Publication Date

5-13-1970

Abstract

Intestinal absorption of neutral amino acids, an active transport process, selects certain amino acids for transfer on the basis of their chemical structure. However, within the group of transported neutral amino acids, selectivity into secondary groups is not readily apparent, and only a relative variation of transport rate for each amino acid has been noted. A popular hypothesis, consistent with previously reported experimental observations, holds that intestinal transport of neutral amino acids occurs through mediation of one transport system with one effective binding site. In the kidney, however, heavy metals have been shown to produce a selective arninoaciduria of primarily hydroxy amino acids, probably by a direct inhibition of renal amino acid transport, indicating that all neutral amino acids are not transported in the same way. A possible similar action on intestinal amino acid transport by mercury, cadmium, and uranium is the experimental problem of this dissertation. If a direct, selective action on amino acid transport is demonstrated, it must be concluded that all neutral amino acids are not transported identically. Net transfer, from mucosal to serosal fluid, of carbon14 amino acids and glucose was determined in everted sacs of rat intestine. Increasing mucosal fluid concentrations of heavy metals produced logarithmic decreases in transport of all amino acids (P< .005), although transport of hydroxy amino acids (serine and threonine) was inhibited more than that of branched-chain amino acids (valine and isoleucine) by mercuric chloride (P< .001), cadmium acetate (P< .05), and uranyl nitrate (P< .001). Slopes of linear regressions calculated by the method of least squares were compared using a two-tailed test based on the Student Distribution. Glucose transport was inhibited to about the same extent as transport of branched-chain amino acids, whereas glucose metabolism and oxygen utilization were less inhibited. Binding of mercury to intestinal tissue, measured with 203mercuric nitrate, demonstrated an interesting concentration dependent pattern of the binding ratio (tissue bound mercury divided by mucosal fluid mercury). As fluid concentration increased, the ratio also increased, consistent with a mercury caused increased cell membrane permeability, allowing the mercury to be bound by intracellular proteins. This pattern is not consistent with simple saturable binding, but suggests, as does the relative extent of transport inhibition compared to inhibition of glucose metabolism and oxygen utilization, that the primary action of mercury is on the cell membrane. Two conclusions, justified by the data obtained in this study, are (a) transport of amino acids is probably inhibited by a direct action of heavy metals and not secondarily through the inhibition of another cell function, and (b) the system for intestinal transport of hydroxy amino acids (serine and threonine) is different in some way from that for branched-chain amino acids.

Document Type

Dissertation

Language

English

Degree Name

Biomedical Sciences

Level of Degree

Doctoral

Department Name

Biomedical Sciences Graduate Program

First Committee Member (Chair)

Unknown

Second Committee Member

Francis Newton Lebaron

Third Committee Member

Aaron J. Ladman

Fourth Committee Member

Robert Samuel Stone

Fifth Committee Member

Joseph Victor Scaletti

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