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Characterisation of tolbutamide hydroxylase activity in the common brushtail possum, (Trichosurus vulpecula) and koala (Phascolarctos cinereus): inhibition by the Eucalyptus terpene 1,8-cineole

Citation

Liapis, P and Pass, GJ and McKinnon, R and Stupans, I, Characterisation of tolbutamide hydroxylase activity in the common brushtail possum, (Trichosurus vulpecula) and koala (Phascolarctos cinereus): inhibition by the Eucalyptus terpene 1,8-cineole, Comparative Biochemistry and Physiology Part C, 127, (3) pp. 351-357. ISSN 0742-8413 (2000) [Refereed Article]


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DOI: doi:10.1016/S0742-8413(00)00163-8

Abstract

Plant constituents such as terpenes are major constituents of the essential oil in Eucalyptus sp. 1,8-Cineole and p-cymene (Terpenes present in high amounts in Eucalyptus leaves) are potential substrates for the CYP family of enzymes. We have investigated tolbutamide hydroxylase as a probe substrate reaction in both koala and terpene pretreated and control brushtail possum liver microsomes and examined inhibition of this reaction by Eucalyptus terpenes. The specific activity determined for tolbutamide hydroxylase in the terpene treated brushtails was significantly higher than that for the control animals (1865ą334 nmol/mg microsomal protein per min versus 895ą27 nmol/mg microsomal protein per min). The activity determined in koala microsomes was 8159ą370 nmol/mg microsomal protein per min. Vmax values and Km values for the terpene treated possum, control, possum and koala were 1932–2225 nmol/mg microsomal protein per min and 0.80–0.81 mM; 1406–1484 nmol/mg microsomal protein per min and 0.87–0.92 mM and 5895–6403 nmol/mg microsomal protein per min and 0.067–0.071 mM, respectively. Terpenes were examined as potential inhibitors of tolbutamide hydroxylase activity. 1,8-Cineole was found to be a competitive inhibitor for the enzyme responsible for tolbutamide hydroxylation (Ki 15 ėM) in the possum. In koala liver microsomes stimulation of tolbutamide hydroxylase activity was observed when concentrations of cineole were increased. Therefore, although inhibition was observed, the type of inhibition could not be determined.

Item Details

Item Type:Refereed Article
Keywords:brushtail possum, koala, cytochrome P450, eucalyptus, induction, terpenes, tolbutamide hydroxylation
Research Division:Medical and Health Sciences
Research Group:Pharmacology and Pharmaceutical Sciences
Research Field:Basic Pharmacology
Objective Division:Environment
Objective Group:Flora, Fauna and Biodiversity
Objective Field:Forest and Woodlands Flora, Fauna and Biodiversity
Author:Pass, GJ (Ms Georgia Jane Pass)
ID Code:19816
Year Published:2000
Web of Science® Times Cited:11
Deposited By:Pharmacy
Deposited On:2000-08-01
Last Modified:2013-09-02
Downloads:0

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