DEVELOPMENTAL AND GENETIC STUDIES ON KYNURENINE HYDROXYLASE FROM DROSOPHILA MELANOGASTER

Abstract

The level of kynurenine hydroxylase was measured throughout the development of wild type and the eye color mutants v, cn, st, ltd, cd, kar, w, ca, bri and pP of Drosophila melanogaster. In all cases except cn a bimodal distribution of enzyme activity during development was observed. Activity is initially detectable in second instar. A maximum is reached in early third instar. Activity declines prior to puparium formation. Shortly after pupation, activity rises dramatically to reach a maximum about five times the peak larval level. Maximum activity persists for a short time, and then falls sharply prior to emergence. No activity is detectable in cn, cn3, or cn35K. In pupae which have zero, one, two or three doses of the cn + allele, activity is proportional to the number of the + alleles. This provides further evidence that the cn locus contains the structural gene for kynurenine hydroxylase. Kynurenine hydroxylase is a useful gene product for studying the events of imaginal disc differentiation.

Effect of Tryptophan Metabolites on Fluorescent Granules in the Malpighian Tubules of Eye Color Mutants of Drosophila melanogaster

“…The wild type alleles of v, cn, st, ltd and w encode products that are required for the brown pigmentation. Two of them, v and cn are nonautonomous mutants and encode the enzymes tryptophan oxygenase (Baglioni, 1959(Baglioni, , 1960Kaufman, 1962;Baillie and Chovinick, 1971) and kynurenine-3-hydroxylase (Ghosh and Forrest, 1967;Sullivan et al, 1973), respectively. The roles of the autonomous mutant genes st, ltd and whave not been clarified.…”

“…Malpighian tubules in D. melanogaster are known to be sources of two precursors of brown pigment, kynurenine and 3-hydroxy-kynurenine (3-HK) (Beadle, 1937a,b;Wessing and Danell, 1961;Eichelberg, 1968, 1972;Sullivan and Sullivan, 1975) and kynurenine-3-hydroxylase activity can be detected only in larval tissue (Sullivan et al, 1973;Sullivan and Sullivan, 1975). During the larval stage, tryptophan metabolites are taken up by the tubules and the stores of pigment precursors are released into the haemolymph at the time of pupation (Beadle, 1937a,b).…”

Modulating the Kynurenine pathway or sequestering toxic 3-hydroxykynurenine protects the retina from light-induced damage in Drosophila

“…This led to the suggestion that loss of st leads to accumulation of 3OH-K outside the LRO [26,41]. In line with this, we hypothesized that excess cytoplasmic 3OH-K levels are responsible for the enhancing effects on the w ndelT retinal phenotype upon removal of one copy of st. To test this hypothesis, we utilized mutations in cinnabar (cn), the gene that encodes kynurenine monooxygenase (KMO), an enzyme that catalyzes the formation of 3OH-K from Kynurenine [46][47][48] (Fig 1A). We expected that reduced levels of 3OH-K by lowering or removing cn activity should attenuate the detrimental effects exerted by loss of st on the w ndelT phenotype.…”

Modulating the Kynurenine pathway or sequestering toxic 3-hydroxykynurenine protects the retina from light induced damage in Drosophila

“…This led to the suggestion that loss of st leads to accumulation of 3OH-K outside the LRO (Cunningham et al, 2018, Mackenzie et al, 2000. In line with this, we hypothesized that excess cytoplasmic 3OH-K levels are responsible for the enhancing effects on the w ndelT retinal phenotype upon removal of one copy of st. To test this hypothesis, we utilized mutations in cinnabar (cn), the gene that encodes kynurenine monooxygenase (KMO), an enzyme that catalyzes the formation of 3OH-K from Kynurenine (Ghosh & Forrest, 1967, Sullivan, Kitos et al, 1973, Warren, Palmer et al, 1996 (Fig. 1A).…”