Glycine conjugation activity of benzoic acid and its acinar localization in the perfused rat liver.
Glycine conjugation activity of benzoic acid and its acinar localization in the perfused rat liver.
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发表时间：
1994
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通讯作者：
M. Chiba;K. Poon;J. Hollands;K. Pang
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作者：
M. Chiba;K. Poon;J. Hollands;K. Pang
在单次灌流大鼠肝脏制备过程中，研究了甘氨酸与苯甲酸(BA)的偶联活性。在示踪剂至700微米的灌注量中，门静脉(PV)灌流肝脏(10毫升/分钟)的稳态肝萃取率在输入浓度为40微米时最大(0.6)。甘氨酸结合是主要途径；在适当校正血浆蛋白结合(Ka=8.37×10(3)M-1和1.9个位点)后估计的动力学参数显示低Km(12微米)和中等高Vmax(101nmol.min-1.g-1肝脏)系统。BA及其甘氨酸偶联代谢物马尿酸的胆汁排泄量很小。在一级条件下(输入浓度2微米)，采用HAPV和HAHV灌流的方法(微量[14C]苯甲酸盐经肝动脉(HA)以2ml/min的速度给药，空白灌流液以10ml/min的速度经门静脉(PV)或肝静脉(HV)灌流)来检测甘氨酸与BA的偶联活性。在稳定状态下，将多指示剂51Cr标记的红细胞(血管标记物)、[58Co]EDTA(间质间隙标记物，其作用类似于标记示踪剂蔗糖)和3H2O(细胞标记物)作为团注注入HA。在HAHV灌流过程中BA的萃取率(0.59+/-0.09)显著降低(0.061+/-0.033，P<；.01)。
Glycine conjugation activity toward benzoic acid (BA) was studied in the single-pass perfused rat liver preparation. The steady-state hepatic extraction ratio for the portal vein (PV) perfused liver (at 10 ml/min) was maximal (0.6) at input concentrations < 40 microM among perfusions varying from tracer to 700 microM. Glycine conjugation was the predominant pathway; the kinetic parameters estimated after appropriately correcting for plasma protein binding (KA = 8.37 x 10(3) M-1 and 1.9 sites) revealed a low Km (12 microM) and a moderately high Vmax (101 nmol.min-1.g-1 liver) system. Biliary excretion of BA and its glycine-conjugated metabolite, hippuric acid, was minimal. Under first-order conditions (input concentration < 2 microM), the method of HAPV and HAHV perfusion (trace [14C]benzoate delivered via the hepatic artery (HA) at 2 ml/min and blank perfusate via the portal vein (PV) or hepatic vein (HV) at 10 ml/min) was used to examine the localization of glycine conjugation activity toward BA. During steady state, a multiple indicator dose of 51Cr-labeled red blood cells (vascular marker), [58Co]EDTA (interstitial space marker, which behaves similar to labeled tracer sucrose) and 3H2O (cellular marker) was injected as a bolus into the HA. Values of the extraction ratio of BA for HAPV perfusion (0.59 +/- 0.09) were dramatically reduced during HAHV perfusion (0.061 +/- 0.033, P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)