Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A sensitive, specific, and simple method for determining serum or urine arylesterase (EC 3.1.1.2) is described. The enzyme acts on phenyl acetate to release phenol, which produces a stable indophenol dye with 4-aminoantipyrine and potassium ferricyanide. Arylesterase, a thiol enzyme, is reactivated by 2-mercaptoethanol and by cysteine, but not by reduced glutathione. Calcium is indispensable to stabilize and to activate (Km = 0.85 mmol/L) the enzyme; complete protection is achieved at CaCl2 20 mmol/L. Magnesium acts as a weak (Ki = 116 mmol/L), lanthanum as a potent (Ki = 5 mumol/L) competitive inhibitor. The activity is measured in diluted sera at phenyl acetate 4.0 mmol/L (Km = 1.12 mmol/L), pH 7.8 and 25 degrees C. The normal range extends from 53 to 186 kU/L, and four isoenzymes are present in sera from healthy adults. Arylesterase decreases in hepatic disorders, especially in cirrhosis and carcinoma of the liver, with reduction of the penultimate fraction in polyacryalmide gel electrophoresis.
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PMID:Arylesterase in serum: elaboration and clinical application of a fixed-incubation method. 47 20

Serum zinc concentrations are decreased in patients with a variety of clinical disorders including cirrhosis, nephrotic syndrome and renal insufficiency. Urinary zinc excretions are increased in the first two disease states. Symptoms of acute zinc deficiency (anorexia, dysfunction of smell and taste, and mental and cerebellar disturbances) and chronic zinc deficiency (growth retardation, anemia, testicular atrophy, and impaired wound healing) are common in these patients. It remains unresolved whether these disease states are indicative of true symptomatic or asymptomatic zinc deficiency or merely reflect a decrease in available zinc binding proteins. The low serum zinc concentrations and high urinary zinc excretions in patients with nephrotic syndrome do not appear to be due to loss of zinc bound to urinary proteins. Studies in dogs indicate increased serum and urine concentrations of certain amino acids(cysteine, histidine) greatly increase urinary zinc excretions. Studies are now underway to determine if the hyperzincuria and hypozincemia of cirrhosis, nephrotic syndrome and hyperalimentation can be explained by an increase in these urinary amino acids.
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PMID:Zinc metabolism in renal disease and renal control of zinc excretion. 60 38

Control subjects and patients with liver diseases (cirrhosis, fatty liver) were given an oral methionine load with 100 mg L-Met/kg body weight. Amino acid chromatography was made by a short-program particularly suitable for the diagnosis of hereditary disorders of methionine metabolism. Met-tolerance in blood plasma as well as cystathionine, homocystine and the mixed disulfide homocysteine-cysteine in plasma and urine were investigated. Methylmalonic acid excretion in the urine was determined by gas chromatography. Patients with liver diseases showed some pathological changes of methionine tolerance after the load. However, cystathionine and homocysteine could not be demonstrated. No methylmalonic acid excretion occurred in normal subjects and patients with liver diseases after the methionine load.
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PMID:[Results of oral methionine loads in normal subjects and patients with liver diseases using an analyzer short program]. 61 59

The effect on free plasma amino acids before and after infusion of 1 mg glucagon was studied at rest after an overnight fast in seven patients with compensated liver cirrhosis and in seven healthy controls. Total aminoacidaemia in cirrhotic patients is significantly higher than in controls. Elevated basal levels in cirrhotics are found particularly in tyrosine, citrulline, tryptophane, threonine, phenylalanine, and methionine whereas ornithine and serine levels are decreased. Save for the redox couple cystine-cysteine which increases, glucagon elicits an decrease in most amino acids that is proportionate to their initial level. Total aminoacidaemia decreases in controls and cirrhotics by 14.6 and 9.1 per cent respectively. Serum ammonia level rises significantly in both groups, urea increases only in controls, uricaemia remains virtually unchanged.
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PMID:The effect of glucagon on free plasma amino acids in cirrhotics and healthy controls. 63 37

When the plasma glutathione concentration is low, such as in patients with HIV infection, alcoholics, and patients with cirrhosis, increasing the availability of circulating glutathione by oral administration might be of therapeutic benefit. To assess the feasibility of supplementing oral glutathione we have determined the systemic availability of glutathione in 7 healthy volunteers. The basal concentrations of glutathione, cysteine, and glutamate in plasma were 6.2, 8.3, and 54 mumol.l-1 respectively. During the 270 min after the administration of glutathione in a dose of 0.15 mmol.kg-1 the concentrations of glutathione, cysteine, and glutamate in plasma did not increase significantly, suggesting that the systemic availability of glutathione is negligible in man. Because of hydrolysis of glutathione by intestinal and hepatic gamma-glutamyltransferase, dietary glutathione is not a major determinant of circulating glutathione, and it is not possible to increase circulating glutathione to a clinically beneficial extent by the oral administration of a single dose of 3 g of glutathione.
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PMID:The systemic availability of oral glutathione. 136 56

Sulfur amino acid metabolism was studied in patients with mild to severe forms of liver dysfunction and compared with that of healthy controls. Patients with mild liver dysfunction (for example, Gilbert's syndrome) had a normal sulfur amino acid metabolism. With increased inflammatory activity and cirrhosis (for example, chronic active hepatitis, alcohol-induced cirrhosis, and hepatic coma) a decreased ability to metabolize methionine (to cysteine, with cystathionine accumulation) and cysteine (to inorganic sulfate, with thiosulfate and N-acetylcysteine accumulation) was found. In contrast, transaminative metabolism of sulfur amino acids was preserved in patients with advanced forms of liver dysfunction, suggesting that transamination of sulfur amino acids is performed not only in the liver but also in extrahepatic tissues. Some implications of these findings are discussed.
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PMID:Sulfur amino acid metabolism in hepatobiliary disorders. 152 76

The liver is actively involved in the metabolism of the sulphur-containing essential amino acid, methionine. Methionine is transformed into S-adenosyl-L-methionine (SAMe) and then into sulphur-containing metabolites (cysteine, taurine and glutathione) via the trans-sulphuration pathway. Liver disease may affect the trans-sulphuration pathway and decrease the clearance of methionine, which leads to increased fasting methionine concentrations in blood and reduced formation of cysteine and glutathione. There is evidence that this defect, located at the level of SAMe-synthetase, may cause nutritional defects and contribute to negative nitrogen balance whenever non-essential sulphur-containing amino acids are not supplied in adequate amounts. In addition, cirrhotic patients may be at increased risk of hepatotoxicity after treatment with substances which are detoxified via glutathione. The SAMe-synthetase block may be overcome by administration of oral or intravenous SAMe, which improves the fasting amino acid profile and increases the hepatic glutathione concentration. Controlled studies on long term SAMe treatment in patients with cirrhosis are needed to confirm this possible beneficial effect.
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PMID:Mechanisms and consequences of the impaired trans-sulphuration pathway in liver disease: Part II. Clinical consequences and potential for pharmacological intervention in cirrhosis. 208 82

The major biological functions of S-adenosyl-L-methionine (SAMe) include methylation of various molecules (transmethylation) and synthesis of cysteine (trans-sulphuration). A stable double salt of SAMe has been found to be effective in intrahepatic cholestasis. The mechanism of its therapeutic effect is not fully understood but presumably involves methylation of phospholipids. Methylation of plasma membrane lipids may affect membrane fluidity and viscosity, which modulate the activities of a number of membrane-associated enzymes, for example, the activity of enzymes involved in Na+/Ca++ exchange (e.g. sarcolemmal vesicles), Na+/K+ adenosine triphosphatase (ATPase) [e.g. hepatocyte plasma membranes], and Na+/H+ exchange (e.g. plasma membranes of colonic cells). Recently, patients with cirrhosis were shown to have an acquired metabolic block in the hepatic conversion of methionine to SAMe. These patients, when administered conventional elemental diets, develop abnormally low plasma concentrations of cysteine and choline, 2 nonessential nutrients present in low concentrations in most elemental diets. These low concentrations probably reflect systemic deficiencies attributable to reduced endogenous syntheses of cysteine and choline caused by limited availability of hepatic SAMe. Such cirrhotic patients are often in negative nitrogen balance and have abnormal hepatic functions, which are corrected by cysteine and choline supplements. Noncirrhotic patients on parenteral elemental diets also become deficient in cysteine and choline. Consequently, these patients may require SAMe as an essential nutrient to normalise their overall hepatic transmethylation and trans-sulphuration activities.
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PMID:Biochemistry and pharmacology of S-adenosyl-L-methionine and rationale for its use in liver disease. 208 85

The content of plasma thiols was determined in 42 patients with non-alcoholic cirrhosis. Total thiols were evaluated by Ellman's method, glutathione and cysteine by HPLC in fluorescence. Cirrhotic patients showed a significant decrease in plasma thiol content with respect to a control group of 32 healthy subjects, as total sulphydryls as well as glutathione and cysteine. The thiol decrease does not seem to be related to nutritional status or dietetic factors. Our data indicate that liver cirrhosis, independently from alcohol abuse, produces a decrease in all plasma thiols, probably secondary to a complex alteration of the transsulfuration pathway.
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PMID:Decrease of total, glutathione and cysteine SH in non-alcoholic cirrhosis. 213 21

Biosynthesis of cysteine from methionine via the hepatic transsulfuration pathway is impaired in some cirrhotic patients, who therefore might require cysteine in the diet. However, because further metabolism of cysteine also occurs primarily in the liver, the metabolic clearance of this amino acid could be impaired in cirrhosis. We administered oral loads of L-cysteine to cirrhotic patients and healthy volunteers. Plasma cyst(e)ine (free and protein-bound cysteine, and 1/2 cystine) and urinary sulfur-containing constituents were measured at various times postload. Cirrhotic subjects exhibited a greater maximal plasma cyst(e)ine concentration and plasma elimination half-life (t1/2) and a delayed excretion of metabolic end products after an oral L-cysteine load. The postload increase in total plasma cyst(e)ine was accounted for primarily by an increase in the disulfide form (cystine). These studies show that cirrhotics have an impaired ability to clear cyst(e)ine from the plasma.
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PMID:Hypercysteinemia and delayed sulfur excretion in cirrhotics after oral cysteine loads. 259 29


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