title: Specificity of leucine effect on protein degradation in perfused rat heart.
abstract: 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.
authors.affiliation: Department of Pathology, School of Medicine, Wayne State University, Detroit, MI 48201.
authors.forename: B H
authors.initials: BH
authors.lastname: Chua
mesh_terms: 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
chemical_list: D000605:Amino Alcohols; D007651:Keto Acids; D011506:Proteins; D011773:Pyruvates; C013082:alpha-ketoisocaproic acid; D019289:Pyruvic Acid; D003523:Cycloserine; D007930:Leucine; D005947:Glucose