Metabolismus proteinů a aminokyselin u proteokatabolických stavů - vliv metabolitů leucinu ; Protein and amino acid metabolism in protein catabolic states - effect of leucine metabolites

Protein catabolism and muscle wasting are basic features characterizing the complex metabolic syndrome, called cachexia, which is a severe complication of many diseases, in whose pathogenesis are often participant the systemic inflammatory response and endotoxemia. Branched-chain amino acids (leucine, isoleucine and valine) are not only an important substrate for protein synthesis, but they are also involved in the regulation of protein metabolism, insulin synthesis and secretion, and serve as the source of amino group in the alanine and glutamine formation in the muscle. Not only leucine but also some of its metabolites, - ketoisocaproic acid (KIC) and -hydroxy--methylbutyrate (HMB), have protein anabolic activity and thus some of leucine effects could be induced by these metabolites. In the last years there is paid attention to the HMB, which is used as a supplement for athletes and tested for its potential use in cachexia treatment. The aim of our experiments was to study: 1) endotoxin-induced effect on metabolism of proteins and amino acids in different types of skeletal muscle and the dose dependence of these changes; 2) effects of selected leucine metabolites (KIC and HMB) on the metabolism of proteins and amino acids - in different types of skeletal muscle; under in vivo and in vitro. ; SOUHRN Proteokatabolismus a ztráta svalové hmoty jsou základními znaky charakterizujícími komplexní metabolický syndrom, zvaný kachexie. Ta je závažnou komplikací celé řady onemocnění, na jejichž patogenezi se často podílí systémová zánětová odpověď a endotoxemie. Aminokyseliny s rozvětveným řetězcem (leucin, isoleucin a valin) nejsou pouze významným substrátem pro tvorbu bílkovin, ale podílejí se také na regulaci metabolismu bílkovin, biosyntézy a sekrece inzulínu a slouží jako zdroj aminoskupiny při tvorbě alaninu a glutaminu ve svalu. Proteoanabolickou aktivitu vykazují kromě leucinu také některé jeho metabolity, kyselina -ketoisokapronová (KIC) a -hydroxy--methylbutyrát (HMB), a tudíž některé ze známých účinků ...