Caenorhabditis elegans fluorescent mutants (
flu-1-
flu-4) show altered fluorescence of the lysosome like intestinal granules, when observed under UV light [Babu, 1974, Siddiqui, 1978; Siddiqui and von Ehrenstein, 1980; Siddiqui and Babu, 1980 a, b; and Babu and Bhat, 1980]. Using biochemical techniques, it was shown that the
flu-1 mutant alleles characterized by a bluish purple gut fluorescence possess reduced kynurenine hydroxylase enzyme activity [Siddiqui and Babu, 1980], and the
flu-2 mutant alleles characterized by a pale dull green fluorescence had a block in kyunreniase enzyme activity [Babu and Bhat, 1980]. The C. elegans genomic sequence encodes these two enzymes in the proximity of
flu-1 and
flu-2 loci. R07B7.5 encodes kynurenine hydroxylase, and C15H9.7 encodes kynureninase, respectively [Altschul et al., 1990; Kanehisa, 2012]. Kynurenine pathway is the primary route for tryptophan catabolism in and the starting point for the synthesis of nicotinamide adenine dinucleotide (NAD) in mammals. Dysregulation or overactivation of this pathway can result in immune system activation and accumulation of potentially neurotoxic compounds, resulting in inflammation, depression, cancer, neurodegenerative and behavioral alterations, SARS-COV-2 resistance, and epigenetic modifications. Kynurenine pathway genes are also conserved in C. elegans [van der Goot and Nolan, 2013]. We are investigating genetic and epigenetic consequences of manipulating kyunrenine pathway in C. elegans to reveal key components of the catabolic pathway in C. elegans, to reveal molecules and mechanisms that are shared in human disease. For instance, we may use sequence optimized human ortholg cDNA in a
flu-1 deletion knockout mutant that shows altered bluish purple intestinal fluorescence and reduced kynurenine hydroxylase activity. Human gene variants cDNA can be used to rescue and be examined for the restoration of intestinal fluorescence and the kynurenine hydroxylase enzyme activity, if the cDNA carrying human variant can restore the normal function in the nematode. Such approach may allow examining human lethal and sublethal variants using the C. elegans model, and could elucidate critical molecular mechanisms underlying human disease.