Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
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Target Concepts:
Gene/Protein
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Query: EC:6.4.1.1 (
pyruvate carboxylase
)
1,516
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The hepatoprotective mechanisms of
N-acetylcysteine
(
NAC
) in non-acetaminophen-induced liver injury have not been studied in detail. We investigated the possibility that
NAC
could affect key pathways of hepatocellular metabolism with or without changes in glutathione (GSH) synthesis. Hepatocellular metabolites and high-energy phosphates were quantified from mouse liver extracts by 1H- and 31P-NMR (nuclear magnetic resonance) spectroscopy. 13C-NMR-isotopomer analysis was used to measure [U-13C]glucose metabolism through pyruvate dehydrogenase (PDH) and
pyruvate carboxylase
(PC).
NAC
(150-1,200 mg/kg) increased liver concentrations of GSH from 8.60 +/- 0.48 to a maximum of 12.95 +/- 1.03 micromol/g ww, whereas hypotaurine (HTau) concentrations increased from 0.05 +/- 0.02 to 9.95 +/- 1.12 micromol/g ww. The limited capacity of
NAC
to increase GSH synthesis was attributed to impaired glucose metabolism through PC. However, 300 mg/kg
NAC
significantly increased the fractional 13C-enrichment in Glu (from 2.08% +/- 0.26% to 4.00% +/- 0.44%) synthesized through PDH, a key enzyme for mitochondrial energy metabolism. This effect could be uncoupled from GSH synthesis and was associated with the prevention of liver injury induced by tert-butylhydroperoxide and 3-nitropropionic acid. In conclusion,
NAC
(1) has a limited capacity to elevate GSH synthesis; (2) increases HTau formation linearly; and (3) improves mitochondrial tricarboxylic acid (TCA) cycle metabolism by stimulation of carbon flux through PDH. This latter effect is independent of the capacity of
NAC
to replete GSH stores. These metabolic actions, among other yet unknown effects, are critical for
NAC
's therapeutic value and should be taken into account when deciding on a wider use of
NAC
.
...
PMID:Metabolic insights into the hepatoprotective role of N-acetylcysteine in mouse liver. 1649 3
