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.
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