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

98 Citations (Scopus)

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

Fingerprint

Glutathione
Cysteine
Pediatrics
Nutritional Support
Critical Illness
Pediatric Intensive Care Units
Prodrugs
Energy Intake
Intravenous Infusions
Gas Chromatography
Inpatients
Proteins
Cohort Studies
Prospective Studies

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

Cite this

Cysteine metabolism and whole blood glutathione synthesis in septic pediatric patients. / Lyons, Jeremy; Rauh-Pfeiffer, Astrid; Ming-Yu, Yong; Lu, Xiao Ming; Zurakowski, David; Curley, Martha; Collier, Sharon; Duggan, Christopher; Nurko, Samuel; Thompson, John; Ajami, Alfred; Borgonha, Sudhir; Young, Vernon R.; Castillo, Leticia.

In: Critical Care Medicine, Vol. 29, No. 4, 01.01.2001, p. 870-877.

Research output: Contribution to journalArticle

Lyons, J, Rauh-Pfeiffer, A, Ming-Yu, Y, Lu, XM, Zurakowski, D, Curley, M, Collier, S, Duggan, C, Nurko, S, Thompson, J, Ajami, A, Borgonha, S, Young, VR & Castillo, L 2001, 'Cysteine metabolism and whole blood glutathione synthesis in septic pediatric patients', Critical Care Medicine, vol. 29, no. 4, pp. 870-877. https://doi.org/10.1097/00003246-200104000-00036
Lyons J, Rauh-Pfeiffer A, Ming-Yu Y, Lu XM, Zurakowski D, Curley M et al. Cysteine metabolism and whole blood glutathione synthesis in septic pediatric patients. Critical Care Medicine. 2001 Jan 1;29(4):870-877. https://doi.org/10.1097/00003246-200104000-00036
Lyons, Jeremy ; Rauh-Pfeiffer, Astrid ; Ming-Yu, Yong ; Lu, Xiao Ming ; Zurakowski, David ; Curley, Martha ; Collier, Sharon ; Duggan, Christopher ; Nurko, Samuel ; Thompson, John ; Ajami, Alfred ; Borgonha, Sudhir ; Young, Vernon R. ; Castillo, Leticia. / Cysteine metabolism and whole blood glutathione synthesis in septic pediatric patients. In: Critical Care Medicine. 2001 ; Vol. 29, No. 4. pp. 870-877.
@article{08e7364f28f24b01bc20dae800fd89f1,
title = "Cysteine metabolism and whole blood glutathione synthesis in septic pediatric patients",
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.",
keywords = "Absolute synthesis rate, Children, Cysteine, Fractional synthesis rate, Glutathione, Kinetics, Metabolism, Pediatric sepsis, Sulfur amino acids, Whole blood, [1-C]cysteinyl-glutathione",
author = "Jeremy Lyons and Astrid Rauh-Pfeiffer and Yong Ming-Yu and Lu, {Xiao Ming} and David Zurakowski and Martha Curley and Sharon Collier and Christopher Duggan and Samuel Nurko and John Thompson and Alfred Ajami and Sudhir Borgonha and Young, {Vernon R.} and Leticia Castillo",
year = "2001",
month = "1",
day = "1",
doi = "10.1097/00003246-200104000-00036",
language = "English (US)",
volume = "29",
pages = "870--877",
journal = "Critical Care Medicine",
issn = "0090-3493",
publisher = "Lippincott Williams and Wilkins",
number = "4",

}

TY - JOUR

T1 - Cysteine metabolism and whole blood glutathione synthesis in septic pediatric patients

AU - Lyons, Jeremy

AU - Rauh-Pfeiffer, Astrid

AU - Ming-Yu, Yong

AU - Lu, Xiao Ming

AU - Zurakowski, David

AU - Curley, Martha

AU - Collier, Sharon

AU - Duggan, Christopher

AU - Nurko, Samuel

AU - Thompson, John

AU - Ajami, Alfred

AU - Borgonha, Sudhir

AU - Young, Vernon R.

AU - Castillo, Leticia

PY - 2001/1/1

Y1 - 2001/1/1

N2 - 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.

AB - 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.

KW - Absolute synthesis rate

KW - Children

KW - Cysteine

KW - Fractional synthesis rate

KW - Glutathione

KW - Kinetics

KW - Metabolism

KW - Pediatric sepsis

KW - Sulfur amino acids

KW - Whole blood

KW - [1-C]cysteinyl-glutathione

UR - http://www.scopus.com/inward/record.url?scp=0035053874&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035053874&partnerID=8YFLogxK

U2 - 10.1097/00003246-200104000-00036

DO - 10.1097/00003246-200104000-00036

M3 - Article

VL - 29

SP - 870

EP - 877

JO - Critical Care Medicine

JF - Critical Care Medicine

SN - 0090-3493

IS - 4

ER -