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[Effect of uremic middle molecules removed during hemofiltration on the enzyme activity in rat liver cytosol]
K Konobu1, E Yamamoto, M Toyomoto
1Biochemistry 2, Osaka University of Pharmaceutical Sciences.
Abstract:
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.
Insights
Middle molecules (MM) accumulating in uremic serum impact liver enzymes. Removing MM via hemodialysis (HF) altered aminotransferase and peptidase activity in rat liver cytosol, suggesting MM
Area of Science:
- Biochemistry
- Uremic Toxin Research
- Enzymology
Context:
- Middle molecules (MM) are known biochemical markers in uremic serum.
- Serum alanine aminotransferase activity is often reduced in uremia.
- The specific toxicity of MM on liver enzymes requires further investigation.
Purpose:
- To investigate the toxic effects of middle molecules (MM) on liver enzymes.
- To assess the impact of MM removal by hemodialysis (HF) on specific liver enzymes in rats.
- To analyze the influence of MM characteristics (hydrophobic/hydrophilic) and hemodialysis intervals on enzyme activity.
Summary:
- Middle molecules (MM) were isolated from hemodialysis (HF) fluid and characterized.
- Rat liver cytosol enzymes, including aminotransferases (GOT, GPT) and peptidases (LAP, gamma GTP), were analyzed.
- MM exposure resulted in decreased leucine aminopeptidase (LAP) and GPT activity, and increased gamma-glutamyltranspeptidase (gamma GTP) activity, with minimal differences based on MM type or HF interval.
Impact:
- These findings suggest that middle molecules (MM) may contribute to the pathogenesis of uremic peptides.
- The study provides insights into the biochemical alterations associated with uremia and the potential role of MM in enzyme dysfunction.
- Understanding MM toxicity is crucial for developing targeted therapies for chronic kidney disease complications.