Drosophila Melanogaster as a Model for Molybdo-Flavoenzyme Mediated Protection against Chemical and Physical Stress

摘要: Aldehyde oxidase (AO) and xanthine oxidoreductase (XOR) are molybdo-flavoenzymes (MFEs) involved in the oxidation of hundreds endogenous exogenous aldehydes N-heterocyclic compounds many which drugs, vitamins environmental pollutants. Mutations XOR molybdenum cofactor sulfurase (MCS) genes result a deficiency or dual AO/XOR respectively. At present despite AO being classed as detoxification enzymes definitive experimental proof this has not been assessed any animals thus far. The aim project was to evaluate ry ma-l strains Drosophila melanogaster models for deficiencies respectively determine if MFEs have role protection against chemical physical stress. An additional molecular basis by cloning sequencing MCS gene. Spectrophotometric HPLC assays demonstrated that were able catalyse biotransformation numerous substrates well-scrutinised mammalian orthologs. These included several aromatic pollutants, drugs vitamins. Investigation enzyme activity strain revealed compromised ability biotransform reflected situation human hereditary xanthinuria type I. Both found be unable all tested. results confirmed good testing enzymes. In order test chemoprotection, MFE administered media survivorship monitored. It methylated xanthines toxic XOR-deficient strains. In addition range including N-heterocycles significantly more AO-null This study therefore provides both detoxification. Investigations effect on lifespan had reduced when compared with wild mean approximately 60% 30% ii these The heat cold stress indicated survive, most conditions. chemicals, temperature rescued mutant normal gene reinserted transgenesis. Cloning DNA mal-1 mal-f1 6 bp insertion 23 deletion exon 4 predicted lead alterations deduced protein structure, explaining