4-Methyl-2-oxopentanoic acid

4-Methyl-2-oxopentanoic acid (α-Ketoisocaproic acid) is a metabolite of L-leucine and is involved in energy metabolism. 4-Methyl-2-oxopentanoic acid increases endoplasmic reticulum stress, promotes lipid accumulation in preadipocytes and insulin resistance by impairing mTOR and autophagy signaling pathways. 4-Methyl-2-oxopentanoic acid also causes oxidative damage, leading to cognitive deficits, inhibits α-ketoglutarate dehydrogenase activity, acts as an oxidative phosphorylation uncoupler and metabolic inhibitor. 4-Methyl-2-oxopentanoic acid acts as a nutrient signal and stimulates skeletal muscle protein synthesis. 4-Methyl-2-oxopentanoic acid can be used in the study of maple syrup urine disease^{[1][2][3][4][5]}. In Vitro:4-Methyl-2-oxopentanoic acid (0-300 μM; 2 d) promotes lipid accumulation and adipogenesis in 3T3-L1 preadipocytes^[2].
In Vivo:4-Methyl-2-oxopentanoic acid (4 mol/L; ICV; 1 h and 15 d) causes impairment of habitual memory and long-term memory in rats^[3].
4-Methyl-2-oxopentanoic acid (400 μmol/kg/h; carotid arch injection; single dose injection 60 min) increases porcine skeletal muscle protein synthesis and plasma leucine levels^[4].