Cysteine metabolism and whole blood glutathione synthesis in septic pediatric patients

Jeremy Lyons, Astrid Rauh-Pfeiffer, Yong Ming-Yu, Xiao Ming Lu, David Zurakowski, Martha Curley, Sharon Collier, Christopher Duggan, Samuel Nurko, John Thompson, Alfred Ajami, Sudhir Borgonha, Vernon R. Young, Leticia Castillo

Research output: Contribution to journalArticle

101 Scopus citations

Abstract

Objective: To investigate whole body in vivo cysteine kinetics and its relationship to whole blood glutathione (GSH) synthesis rates in septic, critically ill pediatric patients and controls. Design: Prospective cohort study. Setting: Multidisciplinary intensive care unit and pediatric inpatient units at a children's hospital. Patients: Ten septic pediatric patients and ten controls (children admitted to the hospital for elective surgery). Interventions: Septic patients (age, 31 months to 17 yrs) and controls (age, 24 months to 21 yrs) received a 6-hr primed, constant, intravenous tracer infusion of L-[1-13C]cysteine. Blood samples were obtained to determine isotopic enrichment of plasma cysteine and whole blood [1-13C]cysteinyl-glutathione by gas-chromatography mass spectrometric techniques. The plasma flux and oxidation rate of cysteine and the fractional and absolute synthesis rates of GSH were determined. Septic patients received variable protein and energy intake, as per routine clinical management, and controls were studied in the early postabsorptive state. Measurements and Main Results: Plasma cysteine fluxes were increased in the septic patients when compared with the controls (68.2 ± 17.5 [SD] vs. 48.7 ± 8.8 μmol·kg-1·hr-1; p < .01), and the fraction of plasma cysteine flux associated with oxidative disposal was similar among the groups. The absolute rates of GSH synthesis in whole blood were decreased (p < .01) in the septic patients (368 ± 156 vs. 909 ± 272 μmol·L-1·day-1). The concentration of whole blood GSH also was decreased in the septic group (665.4 ± 194 vs. 1059 ± 334 μM; p < .01) Conclusions: Whole blood glutathione synthesis rates are decreased, by about 60%, in critically ill septic children receiving limited nutritional support. Plasma cysteine fluxes and concentration of cysteine were increased in the septic patients, suggesting a hypermetabolic state with increased protein breakdown. The mechanisms whereby GSH synthesis rates are decreased in these patients are probably multifactorial, presumably involving an inflammatory response in the presence of limited nutritional support. The role of nutritional modulation and the use of cysteine prodrugs in maintaining GSH concentration and synthesis remain to be established.

Original languageEnglish (US)
Pages (from-to)870-877
Number of pages8
JournalCritical Care Medicine
Volume29
Issue number4
DOIs
StatePublished - Jan 1 2001
Externally publishedYes

Keywords

  • Absolute synthesis rate
  • Children
  • Cysteine
  • Fractional synthesis rate
  • Glutathione
  • Kinetics
  • Metabolism
  • Pediatric sepsis
  • Sulfur amino acids
  • Whole blood
  • [1-C]cysteinyl-glutathione

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

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    Lyons, J., Rauh-Pfeiffer, A., Ming-Yu, Y., Lu, X. M., Zurakowski, D., Curley, M., Collier, S., Duggan, C., Nurko, S., Thompson, J., Ajami, A., Borgonha, S., Young, V. R., & Castillo, L. (2001). Cysteine metabolism and whole blood glutathione synthesis in septic pediatric patients. Critical Care Medicine, 29(4), 870-877. https://doi.org/10.1097/00003246-200104000-00036