Mechanisms and consequences of the impaired trans-sulphuration pathway in liver disease: Part II. Clinical consequences and potential for pharmacological intervention in cirrhosis.
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.
Pisi
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Istituto di Clinica Medica Generale e Terapia Medica, Università di Bologna, Italy.
Marchesini
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D000596:Amino Acids / Q000097:blood; D006801:Humans; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000378:metabolism*; D008715:Methionine / Q000378:metabolism* / Q000493:pharmacokinetics; D012436:S-Adenosylmethionine / Q000627:therapeutic use
D000596:Amino Acids; D012436:S-Adenosylmethionine; D008715:Methionine