Hankes and Henderson (I), Gholson et al. (2), and Gholson and Henderson (3) demonstrated that nL-tryptophan-7cu-14C was metabolized by the rat to r4C02 via acetate-1-r4C. Subsequently, Gholson et al. (4) indicated that 3-hydroxyanthranilic acid was an intermediate in the major pathway for the degradation of the benzene ring of tryptophan. Further experiments in viva have provided evidence that ...

Quinolinic acid (QUIN) is a potent endogenous excitotoxin, which has been shown to be present in the brain (Wolfensberger et al., 1983). In order to study the cellular localization of QUIN metabolism in the hippocampus, specific antibodies raised against purified rat liver 3-hydroxyanthranilic acid oxygenase (3HAO) and quinolinic acid phosphoribosyltransferase (QPRT), the enzymes directly respo...

viously reported (Paine et al., 1979b), in the loss of 60% of their total nucleotide content, which is due to a loss of NAD+ and NADH (referred to as NAD throughout) (Table 1). Culture of hepatocytes for 24 h in media containing hyperphysiological concentrations of known precursors of NAD (Ijichi et al., 1966; Blake et al., 1967) shows that only culture medium containing nicotinamide is able to...

The kynurenine pathway (KP) is the principle route of L-Tryptophan (TRP) metabolism, producing several neurotoxic and neuroprotective metabolic precursors before complete oxidation to the essential pyridine nucleotide nicotinamide adenine dinucleotide (NAD(+)). KP inhibition may prove therapeutic in central nervous system (CNS) inflammation by reducing the production of excitotoxins such as qui...

Pain and depression often co-occur, but the underlying mechanisms have not been elucidated. Here, we used the spared nerve injury (SNI) model in mice to induce both neuropathic pain and depression-like behavior. We investigated whether brain interleukin (IL)-1 signaling and activity of kynurenine 3-monoxygenase (KMO), a key enzyme for metabolism of kynurenine into the neurotoxic NMDA receptor a...

Substantial increases in the concentrations of the excitotoxin and N-methyl-D-aspartate-receptor agonist quinolinic acid (QUIN) occur in human patients and non-human primates with inflammatory diseases. Such increases were postulated to be secondary to induction of indoleamine 2,3-dioxygenase in inflammatory cells, particularly macrophages, by interferon-gamma. To test this hypothesis, human pe...