Mitochondrial aspartate aminotransferase: a third kynurenate-producing enzyme in the mammalian brain.

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Guidetti P, Amori L, Sapko MT, Okuno E, Schwarcz R

Mitochondrial aspartate aminotransferase: a third kynurenate-producing enzyme in the mammalian brain.

J Neurochem. 2007 Jul;102(1):103-11. Epub 2007 Apr 17.

PubMed ID

17442055 [ View in PubMed

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Abstract

The tryptophan metabolite kynurenic acid (KYNA), which is produced enzymatically by the irreversible transamination of l-kynurenine, is an antagonist of alpha7 nicotinic and NMDA receptors and may thus modulate cholinergic and glutamatergic neurotransmission. Two kynurenine aminotransferases (KAT I and II) are currently considered the major biosynthetic enzymes of KYNA in the brain. In this study, we report the existence of a third enzyme displaying KAT activity in the mammalian brain. The novel KAT had a pH optimum of 8.0 and a low capacity to transaminate glutamine or alpha-aminoadipate (the classic substrates of KAT I and KAT II, respectively). The enzyme was inhibited by aspartate, glutamate, and quisqualate but was insensitive to blockade by glutamine or anti-KAT II antibodies. After purification to homogeneity, the protein was sequenced and the enzyme was identified as mitochondrial aspartate aminotransferase (mitAAT). Finally, the relative contributions of KAT I, KAT II, and mitAAT to total KAT activity were determined in mouse, rat, and human brain at physiological pH using anti-mitAAT antibodies. KAT II was most abundant in rat and human brain, while mitAAT played the major role in mouse brain. It remains to be seen if mitAAT participates in cerebral KYNA synthesis under physiological and/or pathological conditions in vivo.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Aspartic acid	Aspartate aminotransferase, cytoplasmic	Protein	Humans	Unknown	Not Available	Details