出版社：American Society for Biochemistry and Molecular Biology
摘要：Leukotrienes (LTs) are active lipid mediators derived in the 5-lipoxygenase pathway. LTC4, the primary cysteinyl LT, is cleaved by γ-glutamyl transpeptidase (GGT), resulting in LTD4. We studied the synthesis and metabolism of LTs in three patients with GGT deficiency. LTs were analyzed in urine, plasma, and monocytes after HPLC separation by enzyme immunoassays, radioactivity detection, and electrospray tandem mass spectrometry. Analysis of LTs in urine revealed increased concentrations of LTC4 (12.8–17.9 nmol/mol creatinine; controls, 4 was below the detection limit ( 4 was found to be increased (17.3 ng/ml; controls, 9.6 ± 0.4 ng/ml), whereas LTD4 and LTE4 were below the detection limit ( 4 was found within normal ranges. In contrast to controls, the synthesis of LTD4 and LTE4 in stimulated monocytes was below the detection limit ( 6 cells; controls, 37.1 ± 4.8 cells and 39.4 ± 5.6 ng/106 cells, respectively). The formation of [3H]LTD4 from [3H]LTC4 in monocytes was completely deficient ( Our data demonstrate a complete deficiency of LTD4 biosynthesis in patients with a genetic deficiency of GGT. GGT deficiency represents a new inborn error of cysteinyl LT synthesis and provides a unique model in which to study the pathobiological coherence of LT and glutathione metabolism.
