DEVELOPMENTAL-CHANGES IN PLASMA THIOL-DISULFIDE TURNOVER IN RATS - A MULTICOMPARTMENTAL APPROACH

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 [S-35]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 [S-35]CYSH and [(35)]3CYSS. 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(-l)) 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 (similar to 55%); CYSH, from 81 to 11 (similar to 85%); CYSS (in CYSH equivalents), from 30 to 10 (similar to 67%). 4) Hydrolysis of GSH supplies only similar to 22% of plasma IDR of CYSH in I rats vs. similar to 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.