RT Journal Article
SR Electronic
T1 Aspartate Aminotransferase Generates Proagonists of the Aryl Hydrocarbon Receptor
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 550
OP 556
DO 10.1124/mol.64.3.550
VO 64
IS 3
A1 Mark A. Bittinger
A1 Linh P. Nguyen
A1 Christopher A. Bradfield
YR 2003
UL http://molpharm.aspetjournals.org/content/64/3/550.abstract
AB The aryl hydrocarbon receptor (AHR) binds planar aromatic compounds and up-regulates the transcription of a battery of xenobiotic-metabolizing enzymes. To identify proteins involved in the biosynthesis of endogenous AHR ligands, we screened extracts of various mouse tissues for AHR signaling activity. We found heart extract to activate AHR and identified the active component to be the enzyme aspartate aminotransferase (EC 2.6.1.1). We demonstrate that this transaminase can activate AHR signaling by converting l-tryptophan to indole-3-pyruvate. In turn, indole-3-pyruvate spontaneously reacts in aqueous solution to form a large number of compounds that act as agonists of AHR. Tyrosine and the serotonin-precursor 5-hydroxytryptophan also activate AHR signaling in combination with aspartate aminotransferase, suggesting that 4-hydroxyphenylpyruvate and 5-hydroxyindolepyruvate also act as proagonists of AHR. This study demonstrates that the known tryptophan metabolic-intermediate indole-3-pyruvate is a proagonist of AHR that reacts in aqueous solution to form a variety of AHR agonists.