AJP - Regulatory, Integrative and Comparative Physiology, Vol 267, Issue 2 415-R425, Copyright © 1994 by American Physiological Society
Developmental changes in plasma thiol-disulfide turnover in rats: a multicompartmental approach
M. Ookhtens and A. V. Mittur
Research Service, Department of Veterans Affairs, Los Angeles, California.
Plasma glutathione (GSH), derived principally from the liver, has been
proposed as the main endogenous source of plasma cysteine (CYSH). In an
earlier study in immature (I) and mature (M) rats, with the use of tracer
boluses of intravenous [35S]GSH, we found the movement of the label through
plasma GSH, CYSH, and cystine (CYSS) pools to be incompatible with a series
of precursor-product compartments (GSH-->CYSH-->CYSS). Thus plasma
GSH did not appear to account for sole source of plasma CYSH. To delineate
the quantitative interrelationships of plasma GSH, CYSH, and CYSS in I and
M rats, we used tracer bolus injections of intravenous [35S]CYSH and
[35S]CYSS. The data from the present and previous studies were then used to
develop a comprehensive multicompartmental model that fits the data from
all experiments. Our analysis indicates the following. 1) Plasma CYSH does
not account for the sole intermediate, kinetically homogeneous pool for the
movement of label from GSH to CYSS. 2) Only one-half of the irreversible
disposal rate (IDR; nmol.min-1.ml-1) of plasma GSH in I rats, but all of it
in M rats, is accounted for by hydrolysis to CYSH+CYSS. Thus I rats appear
capable of taking up substantial amounts of plasma GSH intact. 3)
Significant age-related declines take place in the following IDRs: GSH,
from 38 to 18 (approximately 55%); CYSH, from 81 to 11 (approximately 85%);
CYSS (in CYSH equivalents), from 30 to 10 (approximately 67%). 4)
Hydrolysis of GSH supplies only approximately 22% of plasma IDR of CYSH in
I rats vs. approximately 78% in M rats. Thus, in I rats, a sizable inflow
of CYSH from other sources than GSH is required to maintain plasma CYSH. 5)
In contrast, plasma CYSS appears fully supplied through circulating GSH and
CYSH.
