Nitric oxide inhibits specific enzymes in the Krebs cycle and the respiratory chain of rat hepatocyte mitochondria
- Univ. of Pittsburgh, PA (United States)
Nitric oxide (NO) is a highly-reactive molecule produced from L-arginine as recently described. In macrophages and tumor cells, NO inhibits specific mitochondrial enzymes presumably by attacking their intrinsic 4Fe-4S centers. The susceptible enzymes include aconitase of the Krebs cycle and oxidoreductase (complex II) of the electron transport chain. The authors have recently demonstrated that hepatocytes (HC) produce NO in large amounts in response to endotoxin and inflammatory cytokines. To determine whether HC suffer a similar enzyme inhibition, the authors exposed rat HC to increasing concentrations of NO solutions for 5 minutes. The activity of aconitase, complex 1, complex 2, and complex 4 (cytochrome oxidase) was determined by measuring O{sub 2} consumption after addition of enzyme-specific substrates. An NO concentration-dependent inhibition of aconitase, complex 1, and complex 2 was measured. After exposure to 0.6 mM solution, the activity of aconitase was blocked to non-measurable values while complex 1 was reduced to 11 + 8%, and complex 2 to 36 + 2% of the activity of control HC. Complex 4 of the respiratory chain remained intact at 100 + 8%. These data indicate that HC, like other cell types, are susceptible to inhibition of important steps of energy production by NO. As NO is produced in response to septic stimuli, this mechanism may play a role in the metabolic dysfunction of HC in sepsis.
- OSTI ID:
- 5892127
- Report Number(s):
- CONF-9104107-; CODEN: FAJOE
- Journal Information:
- FASEB Journal (Federation of American Societies for Experimental Biology); (United States), Vol. 4:3; Conference: 75. annual meeting of the Federation of American Societies for Experimental Biology (FASEB), Atlanta, GA (United States), 21-25 Apr 1991; ISSN 0892-6638
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
LIVER CELLS
ENZYME ACTIVITY
NITRIC OXIDE
TOXICITY
CYTOCHROME OXIDASE
ENZYME INHIBITORS
HYDRO-LYASES
INFLAMMATION
KREBS CYCLE
MITOCHONDRIA
NITROXYL RADICALS
OXIDOREDUCTASES
RATS
RESPIRATION
ANIMAL CELLS
ANIMALS
CARBON-OXYGEN LYASES
CELL CONSTITUENTS
CHALCOGENIDES
ENZYMES
HAEM DEHYDROGENASES
LYASES
MAMMALS
NITROGEN COMPOUNDS
NITROGEN OXIDES
ORGANIC COMPOUNDS
OXIDES
OXYGEN COMPOUNDS
PATHOLOGICAL CHANGES
PROTEINS
RADICALS
RODENTS
SOMATIC CELLS
SYMPTOMS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology