PANCREATIC CARBOXYPEPTIDASE HYDROLYSIS OF BILE-ACID AMINO-ACID CONJUGATES - SELECTIVE RESISTANCE OF GLYCINE AND TAURINE AMIDATES
PANCREATIC CARBOXYPEPTIDASE HYDROLYSIS OF BILE-ACID AMINO-ACID CONJUGATES - SELECTIVE RESISTANCE OF GLYCINE AND TAURINE AMIDATES
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DOI：
10.1016/0016-5085(86)90925-x
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发表时间：
1986-02-01
期刊：
影响因子：
29.4
通讯作者：
HOFMANN, AF
中科院分区：
文献类型：
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作者：
HUIJGHEBAERT, SM;HOFMANN, AF
为了找出胆汁酸与甘氨酸或牛磺酸选择性肝结合的可能原因，合成了胆酸酰胺酸酯及一些氨基酸和氨基酸类似物，并测定了它们对胰液、胃液、血清或小肠粘膜酶的水解性。还考察了纯羧肽酶A和B的去共轭作用，并与细菌胆甘氨酸水解酶的催化作用进行了比较。人胰液对除甘氨酸外的所有中性L氨基酸(L-丙氨酸、L-缬氨酸、L-亮氨酸、L-酪氨酸)的胆酰结合物均有有效的水解性。当末端残基是芳香族或支链脂肪族时，每小时净水解率(微雄每毫克蛋白质每小时)增加，并且似乎是α-氨基酸所特有的，因为胆基-β-丙氨酸和胆基-d-缬氨酸没有被切割。从胆酰甘氨酸中，只有效地去除了末端的甘氨酸。胆基牛磺酸和胆基与牛磺酸的甲基和丙基类似物的结合物耐水解。两种碱性氨基酸结合物(胆基-L-赖氨酸和胆基-L-精氨酸)被切割，而酸性氨基酸(胆酰-天冬氨酸和胆基-半胱氨酸)的结合物不被切割。使用纯酶的研究表明，牛羧肽酶A以与人胰液相似的特异性水解中性α-氨基酸的胆基结合物，而牛羧肽酶B则裂解碱性氨基酸结合物。胆酰-L-赖氨酸和胆酰-L-精氨酸也被血清和血浆所裂解，已知它们具有羧肽酶活性。胆碱结合物不能被胃液、胰酶或大鼠小肠粘膜匀浆切割。相反，所有的胆碱基偶联物都被细菌胆甘氨酸水解酶切割。这些实验表明，胆酸的甘氨酸和牛磺酸酰胺酸盐不同于其他一些中性和碱性氨基酸的结合物，这是因为它们对胰腺和血浆羧肽酶的水解具有抵抗力。这些数据和其他数据表明，胆酸结合大大减少了被动肠道吸收，表明胆酸与甘氨酸或牛磺酸结合的一个生理功能是形成表面活性物质，这些表面活性物质在近端小肠消化过程中仍然无法消化和相当不可吸收。
To find a possible explanation for the selective hepatic conjugation of bile acids with glycine or taurine, theN-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 micromales per milligram protein per hour) increased when the terminal residue was aromatic or branched aliphatic, and appeared to be specific forl-α-amino acids as cholyl-β-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 neutrall-α-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. These data, together with other data indicating that bile acid conjugation greatly decreases passive intestinal absorption, indicate that a physiologic function of bile acid conjugation with glycine or taurine is to form surfactants that remain indigestible and rather nonabsorbable during digestion in the proximal small intestine.