Fate of the Dietary Terpene, P-Cymene, in the male koala
REBECCA BOYLE,1,* STUART MCLEAN,1 WILLIAM J. FOLEY,2 BEN D. MOORE,2 NOEL W. DAVIES,3 and SUE BRANDON1
1Tasmanian School of Pharmacy, University of Tasmania GPO Box 252-26, Hobart 7001, Tasmania, Australia
2Division of Botany and Zoology Australian National University Canberra 0200, ACT, Australia
3Central Science Laboratory, University of Tasmania GPO Box 252-74, Hobart 7001, Tasmania, Australia
The fate of the dietary terpene, p-cymene, is reported in a specialist Eucalyptus leaf folivore, the koala (Phascolarctos cinereus). Six male koalas were given two single oral doses of p-cymene (0.37 mmol / kg and 1.49 mmol / kg). Urine and feces were collected for two 24-hr periods after each dose and analyzed for metabolites by extraction, gas chromatography, and mass spectrometry. A total of six metabolites were detected in the urine. A novel, extensively oxidized metabolite, 4-(1,2-dihydroxy-1-methylethyl)-benzoic acid, was identiﬁed and its structure elucidated by high resolution and chemical ionization mass spectrometry. Minor amounts of two glycine conjugated metabolites were also detected. Five metabolites were present in sufﬁcient amounts to quantify, using isolated urinary metabolites as reference standards. The mean fractional recovery of administered p-cymene was 0.77 ± 0.09 and 0.84 ± 0.12 for the low and high dose, respectively. The major metabolite excreted was the novel carboxy diol compound. No fecal metabolites were found. Thus, the koala employs a strategy in the metabolism of p-cymene that promotes the production of extensively oxidized metabolites that consequently have increased polarity and enhanced renal excretion. This strategy is compared with that employed by other Eucalyptus leaf folivores.