Specificity of leucine effect on protein degradation in perfused rat heart.
The primary objective of the present study was to assess whether the inhibitory effect of leucine in rat hearts on protein degradation is mediated by leucine itself, alpha-ketoisocaproate (alpha-KIC) or the decarboxylated products of leucine. Protein degradation, as measured by the release of phenylalanine, was inhibited by 1 mM leucine in hearts supplied with glucose, despite low intracellular alpha-KIC concentration (6.3 +/- 0.5 microM). The inhibition of protein degradation by leucine occurred in hearts supplied with pyruvate, a substrate that completely abolished leucine decarboxylation. Under this condition, leucine was transaminated to alpha-KIC. Since the transamination could not be inhibited more than 38% by 10 mM L-cycloserine, it was difficult to exclude that leucine exerted its inhibitory effect via transamination to alpha-KIC. A clear correlation between protein degradation and intracellular leucine or alpha-KIC concentration could not be established. However, a high concentration of leucine (1 mM) or alpha-KIC (0.3 mM) in the perfusate inhibited protein degradation by 30 and 20%, respectively. This suggested that both leucine and alpha-KIC act on the plasma membrane regulatory sites. Of the various structural analogues of leucine that were tested, only L-leucinol inhibited protein degradation. This inhibition could be attributed to a direct lysosomotropic effect of this amino alcohol. The results indicate that high concentrations of extracellular leucine and alpha-KIC appear to inhibit heart protein degradation in vitro.
Chua
B H
BH
Department of Pathology, School of Medicine, Wayne State University, Detroit, MI 48201.
D000605:Amino Alcohols / Q000494:pharmacology; D000818:Animals; D003523:Cycloserine / Q000494:pharmacology; D003653:Decarboxylation; D005947:Glucose / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007651:Keto Acids / Q000032:analysis; D007930:Leucine / Q000032:analysis / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion; D014176:Protein Biosynthesis; D011506:Proteins / Q000378:metabolism*; D011773:Pyruvates / Q000494:pharmacology; D019289:Pyruvic Acid; D051381:Rats; D017207:Rats, Sprague-Dawley
D000605:Amino Alcohols; D007651:Keto Acids; D011506:Proteins; D011773:Pyruvates; C013082:alpha-ketoisocaproic acid; D019289:Pyruvic Acid; D003523:Cycloserine; D007930:Leucine; D005947:Glucose