Kynureninase-type enzymes and the evolution of the aerobic tryptophan-to-nicotinamide adenine dinucleotide pathway

Kynureninase-type enzymes from two strains of Xanthomonas pruni

“…Our analyses of a variety of microorganisms and animals [1,4,9] have shown that the kynureninasetype enzymes, in general, appear to have a fair degree of physiological specificity. It is our belief that, in the course of evolution, most of these organisms have adapted their kynureninase-type activities to the specific functions of either tryptophan catabolism (kynureninases) or NAD biosynthesis (hydroxykynureninases).…”

“…In some organisms the inducible kynureninase may replace the function of a lacking or defective constitutive hydroxykynureninase. We have recently suggested the possibility that the tryptophan-to.NAD pathway evolved from a strictly catabolic set of enzymes [1]. This proposition predicts the occurrence, at some point in the course * To whom correspondence and requests for reprints should be sent at the Biology Division, Oak Ridge National Laborato-r3, Post Office Box Y, Oak Ridge, Tenn. 37830, U.S.A.…”

“…In the sequence of nine enzyme-catalyzed reactions which lead to the biosynthetic transformation of L-tryptophan to the pyridine nucleus of nicotinamide adenine dinucleotide (NAD), we have recently shown in a variety of eukaryotes that the fourth step in the pathway, the hydrolysis of L-3-hydroxykynurenine to 3-hydroxyanthranilate, is catalyzed by a specific constitutive enzyme, which we have characterized as a hydroxykynureninase [1 ]. Alternatively, in some organisms, L-tryptophan is catabolically diverted to anthranilate which is subsequently excreted [2], reused in the biosynthesis of L-tryptophan [3], or converted to other metabolites [2].…”

Initial characterization of a recombinant kynureninase from Trypanosoma cruzi identified from an EST database

“…N-formylkynurenine can also be used as a substrate. Kynureninase has been described in bacteria, fungi, vertebrates (Koushik et al, 1997;Jakoby and Bonner, 1953;Shetty and Gaertner, 1973;Toma et al, 1997;Gaertner and Shetty, 1977;Allegri et al, 2003) and more recently in the only insect known to have a kynureninase gene, the silkworm Bombyx mori (Meng et al, 2009). Two functional orthologs of kynureninase are known.…”

Cloning and recombinant expression of rat and human kynureninase

“…The biochemical properties of kynureninase were studied in mouse, rat and pig liver extracts [3–6]showing that this enzyme is an homodimer of around 95 kDa. It is present in all major classes of vertebrates [7]and can be regarded as a 3‐hydroxykynureninase‐type enzyme, since it hydrolyzes preferentially 3‐OHKYN [8]. The product of this reaction, 3‐OHAA is further utilised to synthesize quinolinic acid (QUINA), whose neurotoxic effect in the CNS is well documented [9].…”