METABOLISM OF STEROID AND AMINO-ACID MOIETIES OF CONJUGATED BILE-ACIDS IN MAN .1. CHOLYLGLYCINE
METABOLISM OF STEROID AND AMINO-ACID MOIETIES OF CONJUGATED BILE-ACIDS IN MAN .1. CHOLYLGLYCINE
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DOI：
10.1172/jci106991
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发表时间：
1972-01-01
影响因子：
15.9
通讯作者：
THOMAS, PJ
中科院分区：
文献类型：
--
作者：
HEPNER, GW;HOFMANN, AF;THOMAS, PJ
对8例留置鼻十二指肠管的健康受试者口服胆酰-2，4-~3H-甘氨酸-1-14C。每隔7天测定胆汁中胆汁酸的放射性分布和胆汁甘氨酸的比活度。测定粪便中的~3H和~(14)C，由~(14)CO_2比活度计算呼气中的~(14)C。甘氨酸部分(平均值±SE，106±17%)的日周转分数是胆汁酸部分(38±7%)的3倍。在某些假设的基础上，计算出在每个肠-肝循环中，大约18%的胆甘氨酸池被去共轭。~(14)C主要在呼吸中被回收(相当于给药剂量的52±5%)，24小时~(14)CO_2排泄量与甘氨酸部分的日周转分数高度相关(r=0.95)，~(3 H)CO_2的排泄主要发生在粪便中，~(14)C的排泄率与日周转分数高度相关(r=0.92)。脱氧胆酰甘氨酸迅速被~3H标记，表明细菌发生了胆碱基的7-脱羟基和对脱氧胆酸的吸收。这一生物转化在所有8个受试者中都发生了，但程度不同，与去卷曲程度无关。由于摄入的甘氨酸-1-14C没有被结合到胆汁酸甘氨酸中，在脱氧胆酰甘氨酸中出现14C(在8个受试者中观察到3个)表明，胆甘氨酸的7-脱羟基可以发生而不需要去共轭作用。当粪便匀浆与甘氨酸胆碱孵育时，体外也观察到脱羟基作用。
Cholyl-2,4-3H-glycine-1-14C was administered orally to eight healthy subjects with indwelling nasoduodenal tubes. The distribution of radioactivity among bile acids and the specific activity of cholylglycine were determined in bile collected at intervals for 7 days.3H and14C were measured in stool.14C in breath was calculated from interval14CO2specific activity determinations.The daily fractional turnover of the glycine moiety (mean ±SE, 106±17%) was three times greater than that of the cholyl moiety (38±7%). On the basis of certain assumptions, it was calculated that about 18% of the cholylglycine pool was deconjugated per enterohepatic cycle. The extent of deconjugation appeared to be unrelated to the efficiency of absorption of the cholyl moiety, which averaged 90-95% per enterohepatic cycle.14C was recovered predominantly in breath (52±5% of administered dose), and 24 hr14CO2excretion correlated highly (r= 0.95) with daily fractional turnover of the glycine moiety.3H excretion occurred predominantly in feces, and the rate correlated highly (r= 0.92) with the daily fractional turnover of the cholyl moiety. Deoxycholylglycine became labeled with3H rapidly, indicating the occurrence of bacterial 7-dehydroxylation of the cholyl moiety and absorption of deoxycholic acid. This biotransformation occurred in all eight subjects but varied in degree and was unrelated to the degree of deconjugation. Since ingested glycine-1-14C was not incorporated into bile acid glycine, appearance of14C in deoxycholylglycine (observed in three of eight subjects) indicated that 7-dehydroxylation of cholylglycine can occur without deconjugation. Dehydroxylation was also observed in vitro when fecal homogenates were incubated with cholylglycine.