Fukagawa N K, Hercules E, Ajami A M
University of Vermont/Fletcher Allen Health Care General Clinical Research Center and Department of Medicine, Burlington, Vermont 05405-0068, USA.
Am J Physiol Endocrinol Metab. 2000 Jan;278(1):E171-6. doi: 10.1152/ajpendo.2000.278.1.E171.
L-2-oxothiazolidine-4-carboxylic acid (OTZ), a 5-oxoproline analog, is metabolized by 5-oxoprolinase and converted to cysteine, the rate-limiting amino acid for GSH synthesis, with the release of CO(2). [(13)C]OTZ (1.5 mg/kg) was used in 12 healthy men and women (ages 23-73 yr) to indirectly assess precursor mobilization for GSH synthesis when stores were reduced by 2 g acetaminophen. Expired breath samples were analyzed for (13)CO(2), and results were analyzed using noncompartmental and two-compartment open minimal models. Results show an increase in (13)C excretion (higher OTZ hydrolysis) when GSH stores were reduced and 5-oxoprolinase substrate utilization patterns, consequently, were altered (P < 0. 01). A metabolic rate index (MRI) of the OTZ probe was found to be significantly higher after reduction of GSH content by acetaminophen (P < 0.05). The difference in adaptive capacity (difference between control and postacetaminophen metabolic rate indexes) was two times as large in the young than the old subjects (P < 0.01). These data support the use of [(13)C]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.
L-2-氧代噻唑烷-4-羧酸（OTZ）是一种5-氧代脯氨酸类似物，可被5-氧代脯氨酸酶代谢并转化为半胱氨酸，半胱氨酸是谷胱甘肽（GSH）合成的限速氨基酸，同时释放出CO₂。12名年龄在23至73岁之间的健康男性和女性使用[(¹³)C]OTZ（1.5毫克/千克），以间接评估当储存量因2克对乙酰氨基酚而减少时GSH合成的前体动员情况。分析呼出气体样本中的(¹³)CO₂，并使用非房室和二房室开放最小模型分析结果。结果显示，当GSH储存量减少且5-氧代脯氨酸酶底物利用模式因此改变时，(¹³)C排泄增加（OTZ水解更高）（P<0.01）。发现对乙酰氨基酚降低GSH含量后，OTZ探针的代谢率指数（MRI）显著更高（P<0.05）。年轻受试者的适应能力差异（对照和对乙酰氨基酚后代谢率指数之间的差异）是老年受试者的两倍（P<0.01）。这些数据支持使用[(¹³)C]OTZ作为一种探针，以识别可能存在GSH储存量低风险或GSH合成能力受损的个体。
