Huijghebaert S M, Hofmann A F
Gastroenterology. 1986 Feb;90(2):306-15. doi: 10.1016/0016-5085(86)90925-x.
To find a possible explanation for the selective hepatic conjugation of bile acids with glycine or taurine, the N-acyl amidates of cholic acid and a number of amino acids and amino acid analogues were synthesized, and their susceptibility to hydrolysis by pancreatic juice, gastric juice, serum, or small intestinal mucosal enzymes was measured. Deconjugation by pure carboxypeptidase A and B was also examined, and hydrolysis by these tissue fluids and enzymes was compared with that mediated by a bacterial cholylglycine hydrolase. Human pancreatic juice efficiently hydrolyzed cholyl conjugates of all neutral-L-amino acids (cholyl-L-alanine, cholyl-L-valine, cholyl-L-leucine, and cholyl-L-tyrosine), except cholylglycine. The net hourly rate of hydrolysis (in micromoles per milligram protein per hour) increased when the terminal residue was aromatic or branched aliphatic, and appeared to be specific for L-alpha-amino acids as cholyl-beta-alanine and cholyl-D-valine were not cleaved. From cholyl glycylglycine, only the terminal glycine was efficiently removed. Cholyltaurine and cholyl conjugates with the methyl and propyl analogues of taurine were resistant to hydrolysis. Two basic amino acid conjugates (cholyl-L-lysine and cholyl-L-arginine) were cleaved, whereas conjugates of acidic amino acids (cholyl-aspartate and cholyl-cysteate) were not cleaved. Studies using pure enzymes showed that bovine carboxypeptidase A hydrolyzed the cholyl conjugates of the neutral L-alpha-amino acids with similar specificity as observed for the human pancreatic juice, whereas bovine carboxypeptidase B cleaved the basic amino acid conjugates. Cholyl-L-lysine and cholyl-L-arginine were also cleaved by serum and plasma, which are known to possess carboxypeptidase activity. Cholyl conjugates were not cleaved by gastric juice, by trypsin, or by homogenates of rat small intestinal mucosa. In contrast, all cholyl conjugates were cleaved by a bacterial cholylglycine hydrolase. These experiments indicate that glycine and taurine amidates of cholic acid differ from a number of other conjugates with neutral and basic amino acid in being resistant to hydrolysis by pancreatic and plasma carboxypeptidases.(ABSTRACT TRUNCATED AT 400 WORDS)
为了找到胆汁酸与甘氨酸或牛磺酸进行选择性肝结合的可能解释，合成了胆酸与多种氨基酸及氨基酸类似物的N-酰基酰胺，并测定了它们对胰液、胃液、血清或小肠黏膜酶水解的敏感性。还检测了纯羧肽酶A和B的去结合作用，并将这些组织液和酶的水解作用与细菌胆酰甘氨酸水解酶介导的水解作用进行了比较。人胰液能有效水解所有中性L-氨基酸的胆酰共轭物（胆酰-L-丙氨酸、胆酰-L-缬氨酸、胆酰-L-亮氨酸和胆酰-L-酪氨酸），但不包括胆酰甘氨酸。当末端残基为芳香族或支链脂肪族时，每小时的净水解速率（以微摩尔每毫克蛋白质每小时计）会增加，并且似乎对L-α-氨基酸具有特异性，因为胆酰-β-丙氨酸和胆酰-D-缬氨酸不会被裂解。从胆酰甘氨酰甘氨酸中，只有末端的甘氨酸能被有效去除。胆酰牛磺酸以及胆酸与牛磺酸的甲基和丙基类似物的共轭物对水解具有抗性。两种碱性氨基酸共轭物（胆酰-L-赖氨酸和胆酰-L-精氨酸）会被裂解，而酸性氨基酸的共轭物（胆酰-天冬氨酸和胆酰-半胱氨酸）不会被裂解。使用纯酶的研究表明，牛羧肽酶A水解中性L-α-氨基酸的胆酰共轭物的特异性与在人胰液中观察到的相似，而牛羧肽酶B能裂解碱性氨基酸共轭物。胆酰-L-赖氨酸和胆酰-L-精氨酸也会被已知具有羧肽酶活性的血清和血浆裂解。胆酰共轭物不会被胃液、胰蛋白酶或大鼠小肠黏膜匀浆裂解。相比之下，所有胆酰共轭物都会被细菌胆酰甘氨酸水解酶裂解。这些实验表明，胆酸的甘氨酸和牛磺酸酰胺与许多其他中性和碱性氨基酸共轭物不同，它们对胰液和血浆羧肽酶的水解具有抗性。（摘要截取自400字）
