title: Inhibition of hepatic methionine adenosyltransferase by peroxides contaminating parenteral nutrition leads to a lower level of glutathione in newborn Guinea pigs.
abstract: Premature newborn infants on total parenteral nutrition (TPN) are at risk of oxidative stress because of peroxides contaminating TPN and low glutathione level. Low cysteine availability limits glutathione synthesis. In this population, the main source of cysteine derives from the hepatic conversion of methionine. The first enzyme of this conversion, methionine adenosyltransferase (MAT), contains redox-sensitive cysteinyl residues. We hypothesize that inhibition of MAT by peroxides contaminating TPN leads to a lower availability of cysteine for glutathione synthesis. At 3 days of life, animals were fitted with a jugular catheter for intravenous infusion. Four groups were compared by ANOVA (P<0.05): (1) Control, without surgery, fed regular chow; (2) Sham, fitted with an obstructed catheter, fed orally regular chow; (3) TPN, fed exclusively TPN (dextrose, amino acids, fat, vitamins) containing 350 μM peroxides; (4) H2O2, fed regular chow orally and infused with 350 μM H2O2. Four days later, MAT activity and glutathione in liver and blood were lower in TPN and H2O2 groups. The redox potential was more oxidized in blood and liver of the TPN group. In conclusion, peroxides generated in TPN inhibit methionine adenosyltransferase activity with, among consequences, a low level of glutathione and a more oxidized redox potential.
authors.affiliation: Department of Pediatrics, CHU Sainte-Justine, University of Montréal, Montréal, Qc, Canada H3T 1C5; Department of Nutrition, CHU Sainte-Justine, University of Montréal, Montréal, Qc, Canada H3T 1C5.
authors.forename: Wesam
authors.initials: W
authors.lastname: Elremaly
authors.affiliation: Department of Pediatrics, CHU Sainte-Justine, University of Montréal, Montréal, Qc, Canada H3T 1C5; Department of Nutrition, CHU Sainte-Justine, University of Montréal, Montréal, Qc, Canada H3T 1C5.
authors.forename: Thérèse
authors.initials: T
authors.lastname: Rouleau
authors.affiliation: Department of Pediatrics, CHU Sainte-Justine, University of Montréal, Montréal, Qc, Canada H3T 1C5; Department of Nutrition, CHU Sainte-Justine, University of Montréal, Montréal, Qc, Canada H3T 1C5. Electronic address: jean-claude.lavoie@umontreal.ca.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Lavoie
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D005506:Food Contamination; D005978:Glutathione / Q000096:biosynthesis / Q000097:blood / Q000172:deficiency*; D006168:Guinea Pigs; D006861:Hydrogen Peroxide / Q000008:administration & dosage / Q000633:toxicity*; D007262:Infusions, Intravenous; D008099:Liver / Q000201:enzymology*; D008716:Methionine Adenosyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016877:Oxidants / Q000008:administration & dosage / Q000633:toxicity*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D057947:Parenteral Nutrition Solutions / Q000008:administration & dosage / Q000633:toxicity*; D010289:Parenteral Nutrition, Total; D047928:Premature Birth / Q000628:therapy
chemical_list: D016877:Oxidants; D057947:Parenteral Nutrition Solutions; D006861:Hydrogen Peroxide; D008716:Methionine Adenosyltransferase; D005978:Glutathione
keywords: GSH; GSSG; Glutathione; H(2)O(2); MAT; Methionine adenosyltransferase; Neonatal; Peroxides; Redox potential; TPN; Total parenteral nutrition; disulfide form of glutathione; hydrogen peroxide; methionine adenosyltransferase (EC 2.5.1.6).; reduced form of glutathione; total parenteral nutrition