Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.469812
Title: Studies on the metabolism of linalool, a naturally occurring food flavour
Author: Rahman, Khandaker A. Q. M.
ISNI:       0000 0001 3504 7501
Awarding Body: University of Surrey
Current Institution: University of Surrey
Date of Award: 1974
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Abstract:
The metabolism of two terpenoid food flavours, linalool. and linalyl acetate, has been studied in the rat. Linalool was labelled with [14]C in the 1- and 2-positions and administered intragastrically to rats; absorption from the gut was rapid. Approximately 58% of the dose was recovered in the urine within 72 hours as linalool, dihydrolinalool and tetrahydrolinalool, mainly conjugated with glucuronic acid or sulphate. Some radioactivity in the urine (10% of dose) was present as [14]C-urea, and 25% of the label appeared as [14]CO[2] in expired air, indicating that linalool entered into pathways of intermediary metabolism. A small proportion of the dose was excreted in the faeces as free and conjugated linalool and as its reduction products. The reduction products of linalool were shown to arise by metabolism occurring in the gut microflora. Both the liver and the intestinal mucosa were shown to conjugate linalool with glucuronic acid in vitro but the activity was much higher in the liver. After intraperitoneal administration of linalool a substantial proportion was excreted as conjugates in the bile and these were hydrolysed in the gut with resultant enterohepatic circulation of linalool and its metabolites. Linalyl acetate was readily hydrolysed in the gut and was subsequently metabolised similarly to linalool. Studies of the effects of linalool on the hepatic drug metabolizing enzymes showed that repeated daily intragastric doses (500 mg/kg body wt. )were required before significant effects on these enzymes were observed. Dosing for up to 64 days caused hepatomegaly with a transient increase of DNA concentration suggestive of hyperplasia as well as cell hypertrophy. Methylumbelliferone glucuronyltransferase activity was increased within 7 days whereas cytochromes P-450 and b[5] underwent a biphasic response being initially inhibited and subsequently increased in concentration. Linalool was shown to interact with cytochrome P-450 in vitro producing a reverse type 1 binding spectrum (K[s] = 1.9 x 10[-4]M) and to inhibit biphenyl-4-hydroxylase (K[i] = 1.9 x 10[-3]M). The observed changes in vivo are indicative of an adaptive response to this mild inhibitor but sensitivity to carcinogens may be increased during the period of hyperplasia. Studies of the metabolism of linalool by the intestinal microflora of rat, mouse, guineapig, sheep, cow and human, revealed substantial interspecies differences. Inter-individual differences in humans appeared to depend on diet. Analysis by GC/MS, i.r. and n.m.r. showed reduction products to be the most common metabolites in most species but a novel intestinal reaction involving cyclisation of linalool to alpha-terpineol and gamma-teipinolene was also observed in some species.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.469812  DOI: Not available
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