Abstract
Glutathione synthetase deficiency (GSD) is an inborn error of glutathione (GSH) metabolism leading to a generalized intracellular GSH defiency. Loukotrione (LT) C4 is derived from the unstable epoxid LTA4 by conjugation with GSH. In the circulation LTC4 is rapidly metabolized to LTE4 which is excreted into the urine. In this study, LT metabolites were separated in a patient with biochemically established GSD by reversed-phase HPLC and quantified by enzyme immunoassays. Results : Our investigations revealed that in GSD LTC4 synthesis is significantly decreased in calcium ionophore activated monocytes as well as in neutrophils ( 11 - 14 % and 7-10 %, respectively, of the levels detected in the parents or controls). Endogenous urinary LTE4 relative to creatinine (nmol/mol) was also found to be abnormally low in GSD (0.4 compared to 15-46 in parents and controls). Conclusions: GSD represents the first described disorder with decreased synthesis of LTs and may serve as a unique; model for the linkage between LT synthesis and GSH metabolism in vivo. Since cysteinyl LTs may be important for cellular functions in the central nervous system, their impaired synthesis might be involved in the pathophysiology of GSD.
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Mayatepek, E., Hoffmann, G., Carlsson, B. et al. IMPAIRED SYNTHESIS OF CYSTEINYL LEUKOTRIENES IN GLUTATHIONE SYNTHETASE DEFICIENCY. Pediatr Res 35, 267 (1994). https://doi.org/10.1203/00006450-199402000-00075
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DOI: https://doi.org/10.1203/00006450-199402000-00075