3-Hydroxyisovaleric acid

β-Hydroxyisovaleric acid is an active metabolite of L-leucine.¹ It is produced from leucine via an α-ketoisocaproic acid intermediate by α-ketoisocaproate oxidase in human liver homogenates. β-Hydroxyisovaleric acid (50 ?M) reduces increases in 20S proteasome activity and NF-κB nuclear accumulation induced by proteolysis-inducing factor (PIF) in C2C12 myotubes.² It inhibits protein degradation and stimulates protein synthesis in the gastrocnemius muscle of cachectic mice bearing MAC16 tumors when administered at doses of 0.25 and 2.5 g/kg.³ Urinary levels of β-hydroxyisovaleric acid are increased in patients with type II diabetes.⁴ Formulations containing β-hydroxyisovaleric acid have been used as dietary supplements.

1.Sabourin, P.J., and Bieber, L.L.Formation of β-hydroxyisovalerate by an α-ketoisocaproate oxygenase in human liverMetabolism32(2)160-164(1983) 2.Smith, H.J., Wyke, S.M., and Tisdale, M.J.Mechanism of the attenuation of proteolysis-inducing factor stimulated protein degradation in muscle by β-hydroxy-β-methylbutyrateCancer Res.64(23)8731-8735(2004) 3.Smith, H.J., Mukerji, P., and M.J., T.Attenuation of proteasome-induced proteolysis in skeletal muscle by β-hydroxy-β-methylbutyrate in cancer-induced muscle lossCancer Res.65(1)277-283(2005) 4.Yu, W.M., Kuhara, T., Inoue, Y., et al.Increased urinary excretion of β-hydroxyisovaleric acid in ketotic and non-ketotic type II diabetes mellitusClin. Chim. Acta188(2)161-168(1990)