Mediated effect of endotoxin and lead upon hepatic metabolism
A test was made of the possibility that gram-negative bacterial cell wall lipopolysaccharides acted directly on key glucoregulatory enzymes in rat liver cytosol to cause the characteristic hypoglycemia of severe endotoxemia. Fasted male rats were sensitized to endotoxin by the simultaneous intravenous injection of lead acetate. The minimum systemic dosage of endotoxin necessary to perturb the normal pattern of hepatic glycolytic intermediates was determined by serial testing with diminishing dosages of endotoxin. The hepatocyte concentration of endotoxin was then calculated from this minimum dosage by use of literature data on the fraction of endotoxin delivered to liver cells after a systemic intravenous injection of radiochromium labeled lipopolysaccharides. Accepting a molecular weight of 118,000 daltons for the smallest endotoxin monomer capable of evoking a physiologic response, the molar amount of endotoxin present in 1 gram of hepatocytes was readily calculated. The concentration of glucoregulatory enzymes in parenchymal cells was then estimated from other literature sources. It was found that the amount of endotoxin in the hepatocytes was insufficient to combine directly with even 1 per cent of the quantity of a single key glucoregulatory enzyme in liver parenchyma. Since a one to one stoichiometric reaction between endotoxin and enzyme could not occur in the liver cytosol, a direct interaction mechanism between agonist and biocatalyst can be ruled out. It is concluded that bacterial endotoxin must act on hepatic glucoregulation by an indirect mechanism presumably based upon the release and operation of mediators.
- Research Organization:
- Univ. of Health Sciences, IL
- OSTI ID:
- 5928031
- Journal Information:
- Surg. Gynecol. Obstet.; (United States), Journal Name: Surg. Gynecol. Obstet.; (United States) Vol. 159:4; ISSN SGOBA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
560305* -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ACETATES
ANIMALS
ANTIGENS
BACTERIA
BIOLOGICAL EFFECTS
BODY
CARBOHYDRATES
CARBOXYLIC ACID SALTS
CELL CONSTITUENTS
CELL WALL
CHEMICAL REACTIONS
CHROMIUM ISOTOPES
DECOMPOSITION
DIGESTIVE SYSTEM
ENDOTOXINS
ENZYMES
ESCHERICHIA COLI
GLANDS
GLYCOLYSIS
ISOTOPE APPLICATIONS
ISOTOPES
LABELLED COMPOUNDS
LEAD COMPOUNDS
LIPIDS
LIPOPOLYSACCHARIDES
LIVER
MAMMALS
MATERIALS
METABOLISM
MICROORGANISMS
ORGANIC COMPOUNDS
ORGANS
POLYSACCHARIDES
RATS
RODENTS
SACCHARIDES
TOXIC MATERIALS
TOXINS
TRACER TECHNIQUES
VERTEBRATES