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Biosynthesis of Isoleucine

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Isoleucine is essential amino acid, only synthesized in plants and bacteria, and required in the diet by animals. In proteins, the hydrophobic Isoleucine side-chain tends to reside with other hydrophobic residues in the interior of globular proteins or in transmembrane domains. Isoleucine biosynthesis begins with the common metabolic intermediate Pyruvate, the endpoint of glycolysis. The first step in Isoleucine biosynthesis requires TPP (Thiamine Pyrophosphate) to form a carbanion intermediate. This intermediate undergoes decarboxylation to produce a stabilized anion of Hydroxyethyl-TPP (HET-PP), which acts as a nucleophile on the Alpha-keto group of a second molecule of Pyruvate or Alpha-ketobutyrate, releasing TPP and Acetolactate or Acetohydroxybutyrate. Another component comes from the amino acid Threonine, which is deaminated to produce Alpha-Ketobutyrate and Ammonia [...]


1.Small molecule functional discrimination of the kinases required for the microbial synthesis of threonine and isoleucine.
Bareich D, Koteva K, Nazi I, Wright GD.
Bioorg Med Chem. 2004 Feb 15;12(4):807-15.
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