The leucine metabolite 3-hydroxy-3-methylbutyrate (HMB) modifies protein turnover in muscles of laboratory rats and domestic chickens in vitro

This study was conducted to assess the in vitro effects of leucine and 3-hy droxy-3-methyl-butyrate (HMB) on protein synthesis and degradation in isola ted rat and chick muscles. Isolated muscles - extensor digitorum longus (ED L) and soleus (S) in rats and EDL and tibialis anterior (TA) in chicks - we re taken out intact and incubated in Krebs-Henseleit buffer with [C-14]phen ylalanine. Protein synthesis was then determined by measuring [C-14]phenyla lanine incorporation into protein and protein breakdown was estimated by ne t release of tyrosine from muscle proteins. In all muscles investigated leu cine stimulated protein synthesis (average 20%; p < 0.05 versus control) bu t only slightly reduced proteolysis (average 8%, NS). In contrast, HMB had no significant effect on protein synthesis but consistently decreased prote in degradation in the range from -29% (p < 0.01 versus control) in rat exte nsor digitorus longus to -5% (NS) in rat soleus muscles. HMB appeared to su ppress protein degradation more in white muscle fibres than in red muscle f ibres (at least in the rat). These data support observations in humans indi cating that HMB decreases muscle proteolysis. It is suggested that metaboli sm of leucine to HMB could be responsible for the reported suppressive effe cts of leucine on protein breakdown.