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Biosynthesis of Leucine

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Leucine is a branched chain essential amino acid whose carbon skeleton originates from Pyruvate. Leucine is a strictly ketogenic amino acid. Alpha-ketoIsovalerate is a precursor for Leucine. The Leucine biosynthesis starts from the oxo acid precursor of Valine and resembles the initial 3 steps of the citrate cycle (Ref.1). The synthesis pathway begins with the condensation of a 2-oxoacid with Hydroxyethyl-TPP, an intermediate of the Pyruvate Dehydrogenase reaction. In this step Pyruvate forms an adduct with TPP (Thiamine Pyrophosphate), which is decarboxylated to hydroxyethyl-TPP. This resonance-stabilized carbanion adds to the keto group of a second pyruvate to form Alpha-Acetolactate. This reaction is catalyzed by Acetolactate synthase. Acetolactate, once formed, get reduced to Alpha-Beta-Dihydroxy-isovalerate via an intermediate. This reaction utilizes single [...]


1.Evolution of the biosynthesis of the branched-chain amino acids.
Keefe AD, Lazcano A, Miller SL.
Orig Life Evol Biosph. 1995 Jun;25(1-3):99-110.
2.Leucine biosynthesis in fungi: entering metabolism through the back door.
Kohlhaw GB.
Microbiol Mol Biol Rev. 2003 Mar;67(1):1-15, table of contents.
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