Shoda J, Tanaka N, Osuga T, Matsuura K, Miyazaki H
Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan.
J Lipid Res. 1990 Feb;31(2):249-59.
C-1 and C-6 hydroxylated bile acid metabolites in various biological specimens from subjects with liver disease (cholestasis, liver cirrhosis, chronic hepatitis, acute hepatitis) were determined by gas-liquid chromatography-mass spectrometry. Five C-1 hydroxylated bile acids and nine C-6 hydroxylated bile acids were identified in the urine studied; 1 beta,3 alpha,12 alpha-trihydroxy-, 1 beta,3 alpha,7 alpha-trihydroxy-, 1 beta,3 alpha,7 alpha,12 alpha-tetrahydroxy-, 3 alpha,6 alpha,7 alpha-trihydroxy-, and 3 alpha,6 alpha,7 alpha,12 alpha-tetrahydroxy-5 beta-cholanoic acids were found as the major components. Most of the 1 beta- and 6 alpha-hydroxylated bile acids were excreted into urine in the nonsulfate-nonglucuronide form. The amounts in the urine were greater than those found in the bile, portal and peripheral venous sera, and liver specimens. The biliary excretion and hepatic extraction of 1 beta-hydroxylated metabolites were more impaired and less efficient than for cholic acid. These findings suggested that hepatic 1 beta- or 6 alpha-hydroxylation of bile acids occurred concurrently in the patients with liver disease and that the resulting hydroxylated metabolites were efficiently excreted in the nonsulfate-nonglucuronide form into urine rather than into bile.
采用气液色谱 - 质谱联用技术测定了患有肝病（胆汁淤积、肝硬化、慢性肝炎、急性肝炎）的受试者各种生物样本中C - 1和C - 6羟基化胆汁酸代谢产物。在所研究的尿液中鉴定出5种C - 1羟基化胆汁酸和9种C - 6羟基化胆汁酸；发现1β,3α,12α - 三羟基 - 、1β,3α,7α - 三羟基 - 、1β,3α,7α,12α - 四羟基 - 、3α,6α,7α - 三羟基 - 和3α,6α,7α,12α - 四羟基 - 5β - 胆烷酸为主要成分。大多数1β - 和6α - 羟基化胆汁酸以非硫酸盐 - 非葡萄糖醛酸苷形式排泄到尿液中。尿液中的含量高于胆汁、门静脉和外周静脉血清以及肝脏样本中的含量。与胆酸相比，1β - 羟基化代谢产物的胆汁排泄和肝脏摄取受损更严重且效率更低。这些发现表明，肝病患者同时发生胆汁酸的肝脏1β - 或6α - 羟基化，并且所产生的羟基化代谢产物以非硫酸盐 - 非葡萄糖醛酸苷形式有效地排泄到尿液中而非胆汁中。
