Decarboxylates branched-chain and aromatic alpha-keto acids to aldehydes. Binds 1 metal ion per subunit. Binds 1 thiamine pyrophosphate per subunit. Allosterically activated by alpha-keto acids and the corresponding amino acids. L-leucine, L-valine, D-valine, L-isoleucine, L-phenylalanine, D-phenylalanine, L-tyrosine and L-valine are activators (with L-leucine and L-isoleucine being the strongest activators) whereas L-tryptophan, tryptophol, phenylacetic acid and indoleacetic acid have no effect. Pyruvate is converted with the lowest catalytic efficiency and displays a weak substrate inhibition. The highest catalytic efficiencies are found for indolepyruvate and alpha-ketoisocaproate. The S0.5 values are 0.26 mM for indolepyruvate, 2.90 mM for alpha-ketoisocaproate, 0.83 mM for phenylpyruvate, 0.92 mM for alpha-ketocaproate, 1.31 mM for alpha-ketovalerate, 0.93 mM for 4-hydroxyphenylpyruvate, 6.68 mM for alpha-keto-beta-methylvalerate, 8.25 mM for benzoylformate, 5=14.17 mM for alpha-ketobutyrate, 24.47 mM for alpha-ketoisovalerate, 98.89 mM for pyruvate. Was identified as a high-confidence drug target. Belongs to the TPP enzyme family.