Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.64 (MPP)
 1,876 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of the present study was to evaluate the effect of mitochondrial inhibitors, 1-methyl-4-phenylpyridinium (MPP(+)) and 3-nitropropionic acid (3-NPA), on the brain production of endogenous glutamate antagonist, kynurenic acid (KYNA). MPP(+) and 3-NPA dose-dependently impaired the synthesis of KYNA in rat cortical slices. Enzymatic studies revealed that MPP(+) inhibits in a concentration-dependent manner the activity of kynurenine aminotransferase II (KAT II), but not the activity of kynurenine aminotransferase I (KAT I). 3-NPA impaired the activity of both enzymes, KAT I and KAT II. Thus, MPP(+)- and 3-NPA-evoked neurotoxicity may be at least partially associated with the depletion of KYNA.
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PMID:1-Methyl-4-phenylpyridinium and 3-nitropropionic acid diminish cortical synthesis of kynurenic acid via interference with kynurenine aminotransferases in rats. 1221 32

Kynurenic acid (KYNA), the only known endogenous glutamate antagonist, is produced in the brain by kynurenine aminotransferases (KATs) I and II. Mitochondrial toxins, 1-methyl-4-phenylpyridinium (MPP +) and 3-nitropropionic acid (3-NPA), were previously shown to reduce KYNA synthesis via interference with KAT I and II. Data presented here demonstrate that immunophilin ligand, FK506 (10-130 microM), but not CsA (1-50 microM), or ryanodine receptor blocker, dantrolene (1-100 microM), enhances the formation of KYNA in cortical slices. FK506, but not CsA or dantrolene, abolished the inhibition of KYNA synthesis evoked by MPP+ and 3-NPA. None of studied compounds influenced the activity of KAT I and KAT II. FK506 is the first among currently used drugs that might stimulate KYNA synthesis. This effect does not seem to arise from the interference with KATs or calcineurin activity.
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PMID:FK506 attenuates 1-methyl-4-phenylpyridinium- and 3-nitropropionic acid-evoked inhibition of kynurenic acid synthesis in rat cortical slices. 1292 36