Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015695 (fatty liver)
 13,941 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Groups of normal and heterozygote sparse-fur (spf) mutant mice were studied at various stages of gestation, to assess the effects of normal pregnancy on orotate excretion, hepatic mitochondrial urea cycle enzymes and any predisposition to the development of fatty liver. Results show a higher total daily excretion of urinary orotate by normal pregnant mice on the 8th and 15th days of gestation, which came to within the usual basal range of excretion of non-pregnant mutant heterozygotes with hereditary ornithine transcarbamylase deficiency. Liver ornithine transcarbamylase and carbamyl phosphate synthetase-I activities were reduced in pregnant mice on the 16th day of gestation (P less than 0.05). No fatty change, bile stasis or glycogen depletion was discernible on optical microscopy in normal or mutant mice. Nonspecific changes were seen on ultrastructural examination. Orotic aciduria seen in pregnant mice may be directly related to a physiological deficiency of liver ornithine transcarbamylase. However, the depletion of both the mitochondrial urea cycle enzymes, seen on the 16th day of pregnancy, may be indicative of a metabolic stress at the mitochondrial level.
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PMID:The role of hepatic ornithine transcarbamylase deficiency in the orotic aciduria of pregnant mice. 373 88

Weanling male Sprague-Dawley rats were fed ad libitum 15% casein diets with and without 5.0% lysine-HCI, 0.25% adenine sulfate or 0.1% allopurinol for 2 weeks. Addition of lysine alone depressed 2-week growth from 94 to 65 g increased average daily urinary orotic acid excretion from 0.39 to 1.77 mg and increased the percentage of total liver lipids from 3.6 to 11.2. Adenine or allopurinol did not change growth but markedly enhanced lysine-induced orotic aciduria and completely prevented lysine-induced fatty livers. Reports by other show that adenine and allopurinol also prevent fatty livers or rats fed arginine-free diets or excess orotic acid. The authors conclude that lysine-induced orotic aciduria results from arginine deficiency caused by antagonism of arginine function by lysine, and that lysine-induced fatty liver probably results from a lesion identical to that produced by feeding excess orotic acid.
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PMID:Fatty liver of growing rats fed excess lysine and its prevention by adenine or allopurinol. 678 27

It is timely to consider the many facets of the small molecule orotic acid (OA), which is well-known as an essential intermediate of pyrimidine de novo synthesis. In addition, it can be taken up by erythrocytes and hepatocytes for conversion into uridine and for use in the pyrimidine recycling pathway. We discuss the link between dietary orotate and fatty liver in rats, and the potential for the alleviation of neonatal hyperbilirubinaemia. We address the development of orotate derivatives for application as anti-pyrimidine drugs, and of complexes with metal ions and organic cations to assist therapies of metabolic syndromes. Recent genetic data link human Miller syndrome to defects in the dihydroorotate dehydrogenase (DHODH) gene, hence to depleted orotate production. Another defect in pyrimidine biosynthesis, the orotic aciduria arising in humans and cattle with a deficiency of UMP synthase (UMPS), has different symptoms. More recent work leads us to conclude that OA may have a role in regulating gene transcription.
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PMID:Orotic Acid, More Than Just an Intermediate of Pyrimidine de novo Synthesis. 2605 69