L-2-[C-13]oxothiazolidine-4-carboxylic acid: a probe for precursor mobilization for glutathione synthesis

L-2-Oxothiazolidine-4-carboxylic acid (OTZ), a 5-oxoproline analog, is meta bolized by 5-oxoprolinase and converted to cysteine, the rate-limiting amin o acid for GSH synthesis, with the release of CO2. [C-13]OTZ (1.5 mg/kg) wa s used in 12 healthy men and women (ages 23-73 yr) to indirectly assess pre cursor mobilization for GSH synthesis when stores were reduced by 2 g aceta minophen. Expired breath samples were analyzed for (CO2)-C-13, and results were analyzed using noncompartmental and two-compartment open minimal model s. Results show an increase in 13C excretion (higher OTZ hydrolysis) when G SH stores were reduced and 5-oxoprolinase substrate utilization patterns, c onsequently, were altered (P < 0.01). A metabolic rate index (MRI) of the O TZ probe was found to be significantly higher after reduction of GSH conten t by acetaminophen (P < 0.05). The difference in adaptive capacity (differe nce between control and postacetaminophen metabolic rate indexes) was two t imes as large in the young than the old subjects (P < 0.01). These data sup port the use of [C-13]OTZ as a probe to identify individuals who may be at risk for low GSH stores or who have an impaired capacity to synthesize GSH.