Recommended Conferences

Neuroscience Psychiatry

Dubai, UAE

2nd International Conference on Clinical Psychiatry

Miami, USA

Psychology and Mental Health

Chicago, USA
Related Subjects
 

Cytochrome P450-dependent metabolism of caffeine in Drosophila melanogaster

Author(s): Coelho A, Fraichard S, Le Goff G, Faure P, Artur Y, Ferveur JF, Heydel JM

Abstract

Caffeine (1, 3, 7-trimethylxanthine), an alkaloid produced by plants, has antioxidant and insecticide properties that can affect metabolism and cognition. In vertebrates, the metabolites derived from caffeine have been identified, and their functions have been characterized. However, the metabolites of caffeine in insects remain unknown. Thus, using radiolabelled caffeine, we have identified some of the primary caffeine metabolites produced in the body of Drosophila melanogaster males, including theobromine, paraxanthine and theophylline. In contrast to mammals, theobromine was the predominant metabolite (paraxanthine in humans; theophylline in monkeys; 1, 3, 7-trimethyluric acid in rodents). A transcriptomic screen of Drosophila flies exposed to caffeine revealed the coordinated variation of a large set of genes that encode xenobiotic-metabolizing proteins, including several cytochromes P450s (CYPs) that were highly overexpressed. Flies treated with metyrapone—an inhibitor of CYP enzymes—showed dramatically decreased caffeine metabolism, indicating that CYPs are involved in this process. Using interference RNA genetic silencing, we measured the metabolic and transcriptomic effect of three candidate CYPs. Silencing of CYP6d5 completely abolished theobromine synthesis, whereas CYP6a8 and CYP12d1 silencing induced different consequences on metabolism and gene expression. Therefore, we characterized several metabolic products and some enzymes potentially involved in the degradation of caffeine. In conclusion, this pioneer approach to caffeine metabolism in insects opens novel perspectives for the investigation of the physiological effects of caffeine metabolites. It also indicates that caffeine could be used as a biomarker to evaluate CYP phenotypes in Drosophila and other insects.

Similar Articles

The impact of coffee on health

Author(s): Cano-Marquina A, Tarín JJ, Cano A

Tolerance to the humoral and hemodynamic effects of caffeine in man

Author(s): Robertson D, Wade D, Workman R, Woosley RL, Oateshttp JA

Caffeine consumption

Author(s): Barone JJ, Roberts HR

Neuropsychiatric effects of caffeine

Author(s): Winston AP, Hardwick E, Jaberi N

Caffeine fatalities – four case reports

Author(s): Holmgren P, Nordén-Pettersson L, Ahlner J

Caffeine metabolism in patients with chronic liver disease

Author(s): Rodopoulos N, Wisén O, Norman A

Assessment of risk involved in the combination medicine of paracetamol and caffeine

Author(s): Uddin MS, Wali MW, Mamun AA, Asaduzzaman M, Amran MS, et al.

Caffeine for the sustainment of mental task performance: Formulations for military operations

Author(s): Vanderveen JE, Armstrong LE, Butterfield GE, Chenoweth WL, Dwyer JT, et al.

Effect of smoking on caffeine clearance

Author(s): Parsons WD, Neims AH

Pharmacokinetic profile of caffeine in the premature newborn infant with apnea

Author(s): Aranda JV, Cook CE, Gorman W, Collinge JM, Loughnan PM, et al.

Pharmacokinetic aspects of theophylline in premature newborns

Author(s): Aranda JV, Sitar DS, Parsons WD, Loughnan PM, Neims AH

Effects of caffeine on visual monitoring

Author(s): Baker WJ, Theologus GC

Seizures and epilepsy after ischemic stroke

Author(s): Camilo O, Goldstein LB

Crude caffeine reduces memory impairment and amyloid ß(1-42) levels in an Alzheimer's mouse model

Author(s): Chu YF, Chang WH, Black RM, Liu JR, Sompol P, et al.