Early effects of dietary orotic acid upon liver lipid synthesis and bile cholesterol secretion in rats
Dietary orotic acid is known to cause impaired fatty acid synthesis and increased cholesterol synthesis in rats. The authors found that the impaired fatty acid synthesis occurs during the first day of orotic acid feeding and, in studies with albumin-bound (1-/sup 14/C)palmitic acid, an associated decrease in the rate of esterification of this fatty acid into triacylglycerol, phospholipid, and cholesteryl ester was observed. These changes may result from the known decreases in liver levels of adenine nucleotides or, as reported here, from decreased liver CoASH levels in orotic acid-fed rats. The increase in hepatic cholesterol synthesis occurred during the second day of orotic acid feeding. It was detected by increased incorporation of (1,2-/sup 14/C)acetate into cholesterol by liver slices and by a 7-fold increase in HMG-CoA reductase activity. At the same time the biliary output of cholesterol was increased 2-fold and studies using /sup 3/H/sub 2/O revealed that the output of newly synthesized cholesterol in bile was increased 5-fold. The content of cholesteryl ester in hepatic microsomes decreased during orotic acid feeding but free cholesterol was unchanged. The findings are interpreted to suggest that the increased bile cholesterol secretion caused by orotic acid is a result of impaired hepatic cholesterol esterification and that the increase in HMG-CoA reductase activity is a result of diminished negative feedback due to the depleted content of cholesteryl ester in the hepatic microsomes.
- Research Organization:
- Univ. of Western Ontario, London, Canada
- OSTI ID:
- 5179967
- Journal Information:
- J. Lipid Res.; (United States), Journal Name: J. Lipid Res.; (United States) Vol. 4; ISSN JLPRA
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
ANIMALS
AZINES
BILE
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
BIOLOGICAL MATERIALS
BIOSYNTHESIS
BODY
BODY FLUIDS
CARBON 14 COMPOUNDS
CARBOXYLIC ACIDS
CHEMICAL REACTIONS
CHOLESTEROL
DIET
DIGESTIVE SYSTEM
ENZYME ACTIVITY
ENZYMES
ESTERIFICATION
GLANDS
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
HEXADECANOIC ACID
HYDROXY COMPOUNDS
INHIBITION
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
LIPIDS
LIVER
MAMMALS
MATERIALS
MONOCARBOXYLIC ACIDS
NUCLEOTIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
OROTIC ACID
OXIDOREDUCTASES
PYRIMIDINES
RATS
REACTION KINETICS
RODENTS
STEROIDS
STEROLS
SYNTHESIS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
URACILS
VERTEBRATES