Marchesini G, Bugianesi E, Bianchi G, Fabbri A, Marchi E, Zoli M, Pisi E
Istituto di Clinica Medica Generale e Terapia Medica, Università di Bologna, Italy.
Hepatology. 1992 Jul;16(1):149-55. doi: 10.1002/hep.1840160125.
A block in the transsulfuration pathway has previously been suggested in cirrhosis on the basis of increased fasting methionine concentrations, decreased methionine elimination and low levels of methionine end products. To date, methionine elimination has never been studied under controlled steady-state conditions, and the relation of the severity of liver disease to impaired methionine metabolism has not been clarified. We measured methionine plasma clearance in 6 control subjects and in 12 patients with cirrhosis during steady-state conditions obtained by a primed, continuous methionine infusion. In the presence of high-normal fasting methionine concentrations (range = 14 to 69 mumol.L-1 in controls and 26 to 151 mumol.L-1 in cirrhotic patients), methionine plasma clearance was reduced in cirrhotic patients (2.25 +/- S.D. 0.43 ml.sec-1 vs. 2.86 +/- S.D. 0.43 ml.sec-1 in controls; p less than 0.05), whereas methionine half-life was increased (282 +/- 90 min vs. 187 +/- 25 min in controls; p less than 0.05). Fasting methionine significantly correlated with methionine clearance. The infused methionine was not degraded to urea to any significant extent in cirrhotic patients, whereas a threefold increase in urinary urea nitrogen excretion rate was observed in controls. Similarly, taurine concentrations significantly increased both in plasma and in the urine in controls but not in cirrhotic patients. In cirrhotic patients methionine plasma clearance significantly correlated with galactose elimination capacity (r = 0.818) and with the Child-Pugh score (rs = -0.795). The study supports a major role of impaired liver cell function in the reduced metabolism of methionine and decreased formation of methionine end products that occur in cirrhosis.(ABSTRACT TRUNCATED AT 250 WORDS)
先前基于空腹蛋氨酸浓度升高、蛋氨酸清除减少及蛋氨酸终产物水平降低，提示肝硬化患者存在转硫途径障碍。迄今为止，从未在可控的稳态条件下研究过蛋氨酸清除情况，且肝病严重程度与蛋氨酸代谢受损之间的关系也未阐明。我们通过给予负荷剂量并持续输注蛋氨酸，在稳态条件下测量了6名对照受试者和12名肝硬化患者的血浆蛋氨酸清除率。在空腹蛋氨酸浓度处于正常高值时（对照组为14至69μmol·L⁻¹，肝硬化患者为26至151μmol·L⁻¹），肝硬化患者的血浆蛋氨酸清除率降低（2.25±标准差0.43ml·sec⁻¹，对照组为2.86±标准差0.43ml·sec⁻¹；p<0.05），而蛋氨酸半衰期延长（282±90分钟，对照组为187±25分钟；p<0.05）。空腹蛋氨酸与蛋氨酸清除率显著相关。在肝硬化患者中，输注的蛋氨酸在很大程度上未降解为尿素，而对照组的尿尿素氮排泄率增加了三倍。同样，对照组血浆和尿液中的牛磺酸浓度显著升高，而肝硬化患者则未升高。在肝硬化患者中，血浆蛋氨酸清除率与半乳糖清除能力显著相关（r = 0.818），与Child-Pugh评分显著相关（rs = -0.795）。该研究支持肝细胞功能受损在肝硬化患者蛋氨酸代谢减少及蛋氨酸终产物形成减少中起主要作用。（摘要截断于250字）
