Figure 1.

Panel A shows the pathway of HMB synthesis from Leucine. The first reaction is the reversible transamination of leucine to α-KIC by BCAA-aminotransferase. This reaction primarily occurs in skeletal muscle. The second reaction, that occurs primarily in the liver, is the is the metabolization of α-KIC by the cytosolic enzyme α-KIC-dioxygenase to produce HMB; panel B shows the mechanisms of action of HMB. HMB increases the protein synthesis via mTOR and by stimulating the production of IGF-1, and reduces the proteolysis through the inhibition of the ubiquitine-proteasome system. HMB also increases the proliferation of satellite cells by the stimulation of MRFs; HMB: Beta-hydroxy-beta-methylbutyrate; α-KIC: alpha-keto-isocaproic acid; BCAA: branched chain amino acids; mTOR: mammalian target of rapamycin; MRFs: Myogenic regulatory factors; IGF-1: insulin-like growth factor 1.