Substitution of Dietary Sulfur Amino Acids by dl-2-Hydroxy-4-Methylthiobutyric Acid Reduces Fractional Glutathione Synthesis in Weaned Piglets.
Amino Acids
/ blood
Amino Acids, Sulfur
/ administration & dosage
Animals
Antioxidants
/ analysis
Biomarkers
/ blood
Cysteine
/ blood
Diet
/ veterinary
Dietary Supplements
Erythrocytes
/ chemistry
Glutathione
/ analysis
Glycine
/ blood
Liver
/ chemistry
Male
Methionine
/ administration & dosage
Oxidative Stress
/ physiology
Sus scrofa
/ metabolism
Weaning
dl-2-hydroxy-4-methylthiobutyric acid
cysteine
fluxes
glutathione synthesis
glycine
pigs
Journal
The Journal of nutrition
ISSN: 1541-6100
Titre abrégé: J Nutr
Pays: United States
ID NLM: 0404243
Informations de publication
Date de publication:
01 04 2020
01 04 2020
Historique:
received:
03
06
2019
revised:
23
07
2019
accepted:
10
10
2019
pubmed:
28
11
2019
medline:
18
8
2020
entrez:
28
11
2019
Statut:
ppublish
Résumé
Cys is limiting for reduced glutathione (GSH) synthesis and can be synthesized from Met. We hypothesized that the dietary Met hydroxyl analogue dl-2-hydroxy-4-methylthiobutyric acid (dl-HMTBA) affects Cys and GSH metabolism and oxidative stress defense differently than Met. The objective was to elucidate whether dl-HMTBA supplementation of a Met-deficient diet affects Cys flux, GSH fractional synthetic rate (FSR), and the basal oxidative stress level relative to Met supplementation in pigs. Twenty-nine male German Landrace piglets aged 28 d were allocated to 3 dietary groups: a basal diet limiting in Met (69% of Met plus Cys requirement) supplemented with either 0.15% l-Met (LMET; n = 9), 0.15% dl-Met (DLMET; n = 11), or 0.17% dl-HMTBA (DLHMTBA; n = 9) on an equimolar basis. At age 54 d the pigs received a continuous infusion of [1-13C]-Cys to calculate Cys flux and Cys oxidation. After 3 d, GSH FSR was determined by [2,2-2H2]-glycine infusion, and RBC GSH and oxidized GSH concentrations were measured. At age 62 d the animals were killed to determine hepatic mRNA abundances of enzymes involved in GSH metabolism, GSH concentrations, and plasma oxidative stress defense markers. The Cys oxidation was 21-39% and Cys flux 5-15% higher in the fed relative to the feed-deprived state (P < 0.001). On average, GSH FSR was 49% lower (P < 0.01), and RBC GSH and total GSH concentrations were 12% and 9% lower, respectively, in DLHMTBA and DLMET relative to LMET pigs (P < 0.05). In the feed-deprived state, Gly flux, the GSH:oxidized glutathione (GSSG) ratio, RBC GSSG concentrations, plasma oxidative stress markers, and the hepatic GSH content did not differ between groups. Although GSH FSR was higher in LMET compared with DLMET or DLHMTBA feed-deprived pigs, these differences were not reflected by lower oxidative stress markers and antioxidant defense enzymes in LMET pigs.
Sections du résumé
BACKGROUND
Cys is limiting for reduced glutathione (GSH) synthesis and can be synthesized from Met. We hypothesized that the dietary Met hydroxyl analogue dl-2-hydroxy-4-methylthiobutyric acid (dl-HMTBA) affects Cys and GSH metabolism and oxidative stress defense differently than Met.
OBJECTIVE
The objective was to elucidate whether dl-HMTBA supplementation of a Met-deficient diet affects Cys flux, GSH fractional synthetic rate (FSR), and the basal oxidative stress level relative to Met supplementation in pigs.
METHODS
Twenty-nine male German Landrace piglets aged 28 d were allocated to 3 dietary groups: a basal diet limiting in Met (69% of Met plus Cys requirement) supplemented with either 0.15% l-Met (LMET; n = 9), 0.15% dl-Met (DLMET; n = 11), or 0.17% dl-HMTBA (DLHMTBA; n = 9) on an equimolar basis. At age 54 d the pigs received a continuous infusion of [1-13C]-Cys to calculate Cys flux and Cys oxidation. After 3 d, GSH FSR was determined by [2,2-2H2]-glycine infusion, and RBC GSH and oxidized GSH concentrations were measured. At age 62 d the animals were killed to determine hepatic mRNA abundances of enzymes involved in GSH metabolism, GSH concentrations, and plasma oxidative stress defense markers.
RESULTS
The Cys oxidation was 21-39% and Cys flux 5-15% higher in the fed relative to the feed-deprived state (P < 0.001). On average, GSH FSR was 49% lower (P < 0.01), and RBC GSH and total GSH concentrations were 12% and 9% lower, respectively, in DLHMTBA and DLMET relative to LMET pigs (P < 0.05). In the feed-deprived state, Gly flux, the GSH:oxidized glutathione (GSSG) ratio, RBC GSSG concentrations, plasma oxidative stress markers, and the hepatic GSH content did not differ between groups.
CONCLUSIONS
Although GSH FSR was higher in LMET compared with DLMET or DLHMTBA feed-deprived pigs, these differences were not reflected by lower oxidative stress markers and antioxidant defense enzymes in LMET pigs.
Identifiants
pubmed: 31773161
pii: S0022-3166(22)02100-9
doi: 10.1093/jn/nxz272
pmc: PMC7138682
doi:
Substances chimiques
Amino Acids
0
Amino Acids, Sulfur
0
Antioxidants
0
Biomarkers
0
alpha-hydroxy-gamma-methylmercaptobutyric acid
583-91-5
Methionine
AE28F7PNPL
Glutathione
GAN16C9B8O
Cysteine
K848JZ4886
Glycine
TE7660XO1C
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
722-729Informations de copyright
Copyright © The Author(s) 2019.
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