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Title:
Single valproic acid treatment inhibits glycogen and RNA ribose turnover while disrupting glucose-derived cholesterol synthesis in liver as revealed by the [U-13C6]-d-glucose tracer in mice | Metabolomics
Description:
Previous genetic and proteomic studies identified altered activity of various enzymes such as those of fatty acid metabolism and glycogen synthesis after a single toxic dose of valproic acid (VPA) in rats. In this study, we demonstrate the effect of VPA on metabolite synthesis flux rates and the possible use of abnormal 13C labeled glucose-derived metabolites in plasma or urine as early markers of toxicity. Female CD-1 mice were injected subcutaneously with saline or 600 mg/kg) VPA. Twelve hours later, the mice were injected with an intraperitoneal load of 1 g/kg [U-13C]-d-glucose. 13C isotopomers of glycogen glucose and RNA ribose in liver, kidney and brain tissue, as well as glucose disposal via cholesterol and glucose in the plasma and urine were determined. The levels of all of the positional 13C isotopomers of glucose were similar in plasma, suggesting that a single VPA dose does not disturb glucose absorption, uptake or hepatic glucose metabolism. Three-hour urine samples showed an increase in the injected tracer indicating a decreased glucose re-absorption via kidney tubules. 13C labeled glucose deposited as liver glycogen or as ribose of RNA were decreased by VPA treatment; incorporation of 13C via acetyl-CoA into plasma cholesterol was significantly lower at 60 min. The severe decreases in glucose-derived carbon flux into plasma and kidney-bound cholesterol, liver glycogen and RNA ribose synthesis, as well as decreased glucose re-absorption and an increased disposal via urine all serve as early flux markers of VPA-induced adverse metabolic effects in the host.
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Keywords {🔍}
glucose, vpa, plasma, tracer, liver, cholesterol, cas, article, google, scholar, urine, glycogen, pubmed, treatment, synthesis, labeled, control, acid, rna, analysis, min, metabolism, toxicity, ribose, mice, single, decreased, animals, isotopomer, journal, dose, isotopomers, mass, fractions, regression, ucdglucose, lee, valproic, brain, enrichment, study, metabolic, expression, treated, turnover, activity, fig, drug, early, injected,
Topics {✒️}
[u-13c6]-d-glucose tracer injected plasma tracer [u-13c6]-d-glucose [u-13c6]-d-glucose tracer [u-13c]-d-glucose tracer /kg [u-13c]-d-glucose glucose-derived 13c-labeled acetate stable low-birth-weight infants [u-13c6]-d-glucose liquid-based cytology media glucose-derived acetate enrichment 13c-labeled glucose showed tracer glucose-derived acetate 13c-labeled positional isotopomers hereditary hemochromatosis-related abnormalities [u-13c3]-dl-lactate sodium di-n-propylacetate lc/ms/ms characterization article download pdf glucose-derived carbon flux amp-dependent kinase signaling full size image 600 mg/kg body weight 13c labeled fractions vehicle treated animals virtually identical [u-13c]glucose acetyl-coa enrichment transfer rna-derived ribose glucose–cholesterol regression curves substrate product cross-talk 13c positional enrichment 13c labeled fraction cholesterol gc/ms analyses mass isotopomer study derived glucose fraction vpa inhibits glucose valproic acid treated 30 mg/ml hydroxylamine hydrochloride tracer substrate flow multi-age rat model tracer glucose substrate mass isotopomer analysis 13c labeled cholesterol control animals exhibited positional 13c isotopomers gene expression profiles 13c labeled carbons vpa treated animals vpa-treated animals tracer substrate study
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headline:Single valproic acid treatment inhibits glycogen and RNA ribose turnover while disrupting glucose-derived cholesterol synthesis in liver as revealed by the [U-13C6]-d-glucose tracer in mice
description:Previous genetic and proteomic studies identified altered activity of various enzymes such as those of fatty acid metabolism and glycogen synthesis after a single toxic dose of valproic acid (VPA) in rats. In this study, we demonstrate the effect of VPA on metabolite synthesis flux rates and the possible use of abnormal 13C labeled glucose-derived metabolites in plasma or urine as early markers of toxicity. Female CD-1 mice were injected subcutaneously with saline or 600 mg/kg) VPA. Twelve hours later, the mice were injected with an intraperitoneal load of 1 g/kg [U-13C]-d-glucose. 13C isotopomers of glycogen glucose and RNA ribose in liver, kidney and brain tissue, as well as glucose disposal via cholesterol and glucose in the plasma and urine were determined. The levels of all of the positional 13C isotopomers of glucose were similar in plasma, suggesting that a single VPA dose does not disturb glucose absorption, uptake or hepatic glucose metabolism. Three-hour urine samples showed an increase in the injected tracer indicating a decreased glucose re-absorption via kidney tubules. 13C labeled glucose deposited as liver glycogen or as ribose of RNA were decreased by VPA treatment; incorporation of 13C via acetyl-CoA into plasma cholesterol was significantly lower at 60 min. The severe decreases in glucose-derived carbon flux into plasma and kidney-bound cholesterol, liver glycogen and RNA ribose synthesis, as well as decreased glucose re-absorption and an increased disposal via urine all serve as early flux markers of VPA-induced adverse metabolic effects in the host.
datePublished:2009-03-31T00:00:00Z
dateModified:2009-03-31T00:00:00Z
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Valproic acid
Stable isotope-based dynamic metabolic profiling (SiDMAP)
[U-13C6]-d-glucose
Biochemistry
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Cell Biology
Developmental Biology
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headline:Single valproic acid treatment inhibits glycogen and RNA ribose turnover while disrupting glucose-derived cholesterol synthesis in liver as revealed by the [U-13C6]-d-glucose tracer in mice
description:Previous genetic and proteomic studies identified altered activity of various enzymes such as those of fatty acid metabolism and glycogen synthesis after a single toxic dose of valproic acid (VPA) in rats. In this study, we demonstrate the effect of VPA on metabolite synthesis flux rates and the possible use of abnormal 13C labeled glucose-derived metabolites in plasma or urine as early markers of toxicity. Female CD-1 mice were injected subcutaneously with saline or 600 mg/kg) VPA. Twelve hours later, the mice were injected with an intraperitoneal load of 1 g/kg [U-13C]-d-glucose. 13C isotopomers of glycogen glucose and RNA ribose in liver, kidney and brain tissue, as well as glucose disposal via cholesterol and glucose in the plasma and urine were determined. The levels of all of the positional 13C isotopomers of glucose were similar in plasma, suggesting that a single VPA dose does not disturb glucose absorption, uptake or hepatic glucose metabolism. Three-hour urine samples showed an increase in the injected tracer indicating a decreased glucose re-absorption via kidney tubules. 13C labeled glucose deposited as liver glycogen or as ribose of RNA were decreased by VPA treatment; incorporation of 13C via acetyl-CoA into plasma cholesterol was significantly lower at 60 min. The severe decreases in glucose-derived carbon flux into plasma and kidney-bound cholesterol, liver glycogen and RNA ribose synthesis, as well as decreased glucose re-absorption and an increased disposal via urine all serve as early flux markers of VPA-induced adverse metabolic effects in the host.
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Valproic acid
Stable isotope-based dynamic metabolic profiling (SiDMAP)
[U-13C6]-d-glucose
Biochemistry
general
Molecular Medicine
Cell Biology
Developmental Biology
Biomedicine
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CDN Services {📦}
- Crossref