Konobu K, Yamamoto E, Toyomoto M, Sawanishi K
Biochemistry 2, Osaka University of Pharmaceutical Sciences.
Nihon Jinzo Gakkai Shi. 1991 Nov;33(11):1105-10.
It is well known that the products of protein catabolism and some of the intermediates including middle molecules (MM) are a biochemical feature of uremic serum and also the activity of serum alanine aminotransferase decreases relatively. To examine the toxicity of MM, we investigate the effect of MM removed by HF on aminotransferases and peptidases in rat liver cytosol. The following enzymes were selected: aminotransferases (GOT, GPT), leucine aminopeptidase (LAP), gamma-glutamyltranspeptidase (gamma GTP). MM samples were as follows: preparation of MM fraction from each 10 l HF fluid at half intervals of former (F-) and latter (L-) for 5 h. HF of two patients (5 weeks) by 1KD ultrafiltration, and group separation into hydrophobic (Mo) and hydrophilic (Mi) by XAD-4 resin (F-Mo, L-Mo, F-Mi, L-Mi). Except for GOT, the effect of MM were found at the activities decreased on LAP (26-30%), on GPT (5-6%), and increased on gamma GTP (4-23%), as compared to control. We found a little difference in the results by the character of MM (Mo, Mi) and by the intervals of HF (F-, L-). These results suggest that MM might play a role in the formation of uremic peptides.
众所周知，蛋白质分解代谢产物以及包括中分子（MM）在内的一些中间产物是尿毒症血清的生化特征，并且血清丙氨酸转氨酶的活性也相对降低。为了研究中分子的毒性，我们研究了通过血液滤过（HF）去除的中分子对大鼠肝细胞溶胶中转氨酶和肽酶的影响。选择了以下几种酶：转氨酶（谷草转氨酶、谷丙转氨酶）、亮氨酸氨肽酶（LAP）、γ-谷氨酰转肽酶（γ-GTP）。中分子样本如下：从每10升血液滤过液中每隔一半时间制备中分子部分，持续5小时，分别从前（F-）和后（L-）获取。两名患者经过5周的1KD超滤血液滤过，并通过XAD-4树脂将其分离为疏水（Mo）和亲水（Mi）组分（F-Mo、L-Mo、F-Mi、L-Mi）。与对照组相比，除了谷草转氨酶外，发现中分子对亮氨酸氨肽酶的活性有降低作用（26%-30%），对谷丙转氨酶有降低作用（5%-6%），而对γ-谷氨酰转肽酶有升高作用（4%-23%）。我们发现，根据中分子的性质（Mo、Mi）以及血液滤过的间隔时间（F-、L-），结果存在一些差异。这些结果表明，中分子可能在尿毒症肽的形成中起作用。
