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)

The activities of pathways for the biosynthesis of hippurate, urea and pyrimidines in hepatocytes isolated from lean livers were compared with those from three sources of fatty liver: a) the genetically obese Zucker rat, b) Sprague-Dawley rats fed a diet deficient in choline and inositol, and c) Sprague-Dawley rats fed a diet supplemented with orotic acid. The capacity for hippurate synthesis was not significantly affected by fat accumulation, but ureagenesis from saturating ammonia and ornithine was diminished about 50% in all models when fat content rose above 12% wet wt of liver. Pyrimidine biosynthesis under these conditions was similarly diminished with fat accumulation. Ureagenesis was inhibited by sodium benzoate in hepatocytes from lean livers, but not in hepatocytes from fatty livers. Other results suggest that higher rates of ureagenesis than could be achieved with the fatty liver are required in order to demonstrate inhibition by benzoate. Incorporation of [14C]NaHCO3 into orotate was also inhibited by sodium benzoate, but in hepatocytes from fatty as well as lean livers. The metabolic basis for impairment of ureagenesis and pyrimidine biosynthesis in the fatty liver requires further study. That the capacity for hippurate synthesis was not significantly affected suggests a pathway-specific mechanism.
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PMID:Biosynthesis of hippurate, urea and pyrimidines in the fatty liver: studies with rats fed orotic acid or a diet deficient in choline and inositol, and with genetically obese (Zucker) rats. 291 1

Young rats were force-fed a lysine + arginine-devoid diet or a complete diet for 3 days, and selected biochemical and morphologic studies were conducted. Rats force-fed the experimental diet in comparison with those force-fed the control diet for 3 days showed decreased body weight gain, hepatomegaly with periportal fatty liver, pancreatic and splenic atrophy, and enhanced 14C-leucine incorporation into hepatic proteins. Differences in the experimental animals were observed in the free amino acid levels of serum (decreased lysine, arginine, and ornithine) and liver (decreased ornithine), in blood chemistries (decreased levels of ammonia N2, uric acid, cholesterol, protein, albumin, alkaline phosphatase, LDH and SGOT) and in hematologic findings (leukocytopenia and thrombocytopenia after a morning feeding). The experimental findings in young rats force-fed the lysine + arginine-devoid diet were compared with those reported to develop in children with lysinuric protein intolerance (LPI), an autosomal recessive defect in diamino acid transport. Children with LPI as described by others reveal a number of similarities as well as a number of differences in comparison to the findings in the experimental animals. The comparison suggests that some of the pathological manifestations of LPI may be related to a deficiency of diamino acids but others must be due to different alterations in this complex human disease.
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PMID:Chemical pathology of diamino acid deficiency: considerations in relation to lysinuric protein intolerance. 393 96

Administration of ethanol to healthy subjects as well as those with alcoholic fatty livers has been noted to cause mild elevation of serum enzyme activities and alcoholic hyperlipemia. To see whether this effect is also manifested in alcoholics with advanced liver damage, the serum enzyme activities and lipid content after administration of i.v. ethanol (1.2 g/kg of body wt) over 90 min were compared in 5 alcoholics with hepatic fibrosis and/or alcoholic fatty liver and in 9 patients with alcoholic hepatitis with or without cirrhosis. Disappearance rate of ethanol from the serum was nearly the same in both groups. Serum activities of asparate aminotransferase, mitochondrial isoenzyme of asparate aminotransferase, and ornithine carbamyl transferase, measured at 9 and 12 hr after termination of the i.v. ethanol, were significantly elevated in alcoholics with alcoholic hepatitis (P less than 0.05). They were not elevated in alcoholics with fatty liver. By contrast, hyperlipemic responses, measured as the serum content of triacylglycerol 3 hr after ethanol were significantly greater in alcoholics with fatty liver than in alcoholics with alcoholic hepatitis (P less than 0.05). The observed difference in responses of serum enzyme activities and lipid content after ethanol represents an enhanced susceptibility of patients with alcoholic hepatitis and cirrhosis towards alcohol-induced injury.
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PMID:Effect of an intravenous infusion of ethanol on serum enzymes and lipids in patients with alcoholic liver disease. 735 55

Juvenile visceral steatosis (JVS) mouse is an animal model of human primary carnitine deficiency caused by a mutation of the gene encoding carnitine transporter, and suffers from various symptoms, such as fatty liver, growth retardation, hyperammonemia, hypoglycemia, and cardiac hypertrophy. We have shown that hyperammonemia during the weaning period (15-26 days of age) is caused by suppression of urea cycle enzyme gene expression. The suppression resulted from activation of a transcription factor, AP-1. We have found that a cis-element for AP-1 binding is present in the enhancer region of the carbamoylphosphate synthetase (CPS) gene, and that the AP-1 binding site is involved in the suppression of CPS induction by dexamethasone in cultured hepatocytes and in the suppression of CPS expression in the liver of JVS mice. The blood ammonia levels in JVS mice increased during the weaning period, and then decreased to almost control levels after 30 days of age. In this paper, we report that in adult JVS mice, ammonia levels again increased after starvation for at least 24 hr and this effect was suppressed by carnitine treatment. Starvation for 48 hr did not significantly suppress CPS activity in the liver and did not cause any change in hepatic ornithine concentration. The concentration of N-acetylglutamate in the liver of starved JVS mice was not significantly different from that of JVS mice treated with carnitine. These results indicate that the hyperammonemia in carnitine-deficient adult JVS mice during starvation and the suppression by carnitine treatment differ from those found during the weaning period, and thus the cause of hyperammonemia and the mechanism of suppression remain to be solved.
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PMID:Hyperammonemia in carnitine-deficient adult JVS mice used by starvation. 1260 12

Wilson disease (WD) is a genetic copper overload condition characterized by hepatic and neuropsychiatric symptoms with a not well-understood pathogenesis. Dysregulated methionine cycle is reported in animal models of WD, though not verified in humans. Choline is essential for lipid and methionine metabolism. Defects in neurotransmitters as acetylcholine, and biogenic amines are reported in WD; however, less is known about their circulating precursors. We aimed to study choline, methionine, aromatic amino acids, and phospholipids in serum of WD subjects. Hydrophilic interaction chromatography-quadrupole time-of-flight mass spectrometry was employed to profile serum of WD subjects categorized as hepatic, neurologic, and pre-clinical. Hepatic transcript levels of genes related to choline and methionine metabolism were verified in the Jackson Laboratory toxic milk mouse model of WD (tx-j). Compared to healthy subjects, choline, methionine, ornithine, proline, phenylalanine, tyrosine, and histidine were significantly elevated in WD, with marked alterations in phosphatidylcholines and reductions in sphingosine-1-phosphate, sphingomyelins, and acylcarnitines. In tx-j mice, choline, methionine, and phosphatidylcholine were similarly dysregulated. Elevated choline is a hallmark dysregulation in WD interconnected with alterations in methionine and phospholipid metabolism, which are relevant to hepatic steatosis. The elevated phenylalanine, tyrosine, and histidine carry implications for neurologic manifestations and are worth further investigation.
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PMID:Dysregulated Choline, Methionine, and Aromatic Amino Acid Metabolism in Patients with Wilson Disease: Exploratory Metabolomic Profiling and Implications for Hepatic and Neurologic Phenotypes. 3177 2