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ELUCIDATION OF TRANSPORT MECHANISMS OF DEHYDRO-L-ASCORBIC ACID, OXIDIZED VITAMIN C (VESICLES, HPLC, ERYTHROCYTE)

Posted on:1986-08-15Degree:Ph.DType:Thesis
University:The Pennsylvania State UniversityCandidate:BIANCHI, JOHN JOSEPHFull Text:PDF
GTID:2471390017460849Subject:Animal physiology
Abstract/Summary:
Vitamin C occurs naturally in a reduced state, L-ascorbic acid, and an oxidized state, dehydro-L-ascorbic acid. Dehydro-L-ascorbic acid has antiscorbutic activity equal to that of L-ascorbic acid. Whereas L-ascorbic acid has been well studied and transport mechanisms have been elucidated, little was known concerning the intestinal absorption and renal reabsorption of dehydro-L-ascorbic acid. In erythrocytes dehydro-L-ascorbic acid uptake has been suggested to be mediated solely by the hexose transporter. Dehydro-L-ascorbic acid has also been described as being cytotoxic. Further, the usual colorimetric qualitative and quantitative analyses for dehydro-L-ascorbic acid are unreliable at physiologic levels. Studies were, therefore, designed: (1) to establish a chromatographic system of analysis, (2) to characterize the transport systems in the luminal and antiluminal membranes of the ileum and kidney, (3) to examine pathway multiplicity in the erythrocyte, and (4) to investigate possible membrane disruptive effects of dehydro-L-ascorbic acid. These studies provided a high-pressure chromatographic analysis coupled with radio-chemical analysis that is capable of quantitating physiologic levels of dehydro-L-ascorbic acid. The uptake of dehydro-L-ascorbic acid is postulated to be by systems of facilitated diffusion in both ileal and renal luminal and antiluminal membranes as demonstrated by tracer flux studies that provide evidence of saturation, cis-inhibition, and trans-stimulation. Transport of dehydro-L-ascorbic acid in the red cell is postulated to be mediated by at least two systems, one of which is independent of the external D-glucose concentration. This glucose-independent system is postulated to be the physiologically relevant pathway of dehydro-L-ascorbic acid uptake into the human erythrocyte. Finally, evidence is presented to support the hypothesis that dehydro-L-ascorbic acid is membrane disruptive.
Keywords/Search Tags:Dehydro-l-ascorbic acid, Erythrocyte, Transport mechanisms, Membrane disruptive
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