Category: catabolism
Beyond the 5-HT / melatonin axis (see serotonin_melatonin_axis), the dominant route for tryptophan (~95% of dietary intake) is the kynurenine pathway → eventually NAD+ via de novo synthesis (see niacin_nad_synthesis). Tryptophan → N-formylkynurenine (IDO in immune cells, TDO in liver) → kynurenine. Branch points: KMO → 3-hydroxykynurenine → quinolinic acid (NMDA agonist; neurotoxic at high concentration) → NAD+. KAT → kynurenic acid (NMDA antagonist; potentially neuroprotective). IDO is upregulated by IFN-γ in tumors as an immune-evasion mechanism — basis for IDO inhibitor oncology trials (epacadostat, etc., mostly negative in phase III). Tryptophan depletion underlies the proposed mechanism of depression in chronic inflammation.