Metabolic Minimap

Products of Isoprene Metabolism

Received for publication, March 21, 2005

Donald Nicholson‡

From the School of Biochemistry and Microbiology, University of Leeds, Leeds L52 9JT, United Kingdom

This minimap (Fig. 1) is one of two that illustrate differentaspects of the same pathway. They are identical biochem-ically, but the Products of Isoprene Metabolism minimaphas a specific purpose, to illustrate something of the fas-cinating variety of well known products that can arise frommultiples of this five carbon compound (C10, C15, C20,C30, and C40) and much bigger. Isoprene itself can beproduced by trees and plants and can create a massiveemission into the atmosphere that sometimes results inblue hazes, as in the Blue Ridge Mountains of Virginia. Atthe other end of the scale, natural rubbers can be polymersof thousands of isoprene residues.

Terpenes (C10) are products of two isoprene units andcan provide color, smell, and flavor to many plant prod-ucts. Limonene, citronellal, menthol, pinene, and cam-phene all speak for themselves. Geraniol contributes to theperfume of roses and geraniums and to the flavor of a widevariety of fruits. Plant and insect hormones and the side-chains of many vitamins and of chlorophyll involve varyingmultiples of isoprene units. Diterpenes (C20) are funda-mentally important. They include phytol, the side-chain ofchlorophyll, and retinal, which helps convert light into vi-sion, as well as powerful plant hormones such as gibberel-lins. Tetraterpenes (C40) include the carotenoids, which

provide not only color to tomatoes and carrots but also thelight harvesting pigments for photosynthesis and autumncolor of trees when the green has gone.

The other pathway diverges at the C15 stage and in thehistoric past led to sterol-like compounds, the hopanoids,the little known pentacyclic compounds present in micro-organisms and in sediments and crude oils. They are saidto be the most abundant organic molecules in the bio-sphere, exceeding even that of cellulose. Sterol synthesisitself takes place via cholesterol and produces a widevariety of hormones including estrogens and testosteroneswith all their implications. Many of the sensual (and sexual)pleasures of life can thus be seen to derive from the samesimple five carbon compound, isoprene.

An altogether different aspect of isoprene metabolism isillustrated at the southeast corner of the minimap andshows the clinical value of drugs that act by inhibitingenzyme activity. Many breast tumors are sensitive to es-trogen, which is metabolized from testosterone by theenzyme aromatase. Drugs such as Letrozol can inhibit theactivity of the enzyme and thus block the production ofestrogen in some tissues.

Enlarged prostate is a common complaint of older men(such as me!), but Finaseride and other drugs can shrinkthe gland by inhibiting testosterone dehydrogenase, theenzyme that converts testosterone to its active reducedform. REAL-LIFE METABOLISM!

‡ To whom correspondence should be addressed: Schoolof Biochemistry and Microbiology, University of Leeds, LeedsL52 9JT, UK. E-mail: d.nicholson@leeds.ac.uk.

© 2005 by The International Union of Biochemistry and Molecular Biology BIOCHEMISTRY AND MOLECULAR BIOLOGY EDUCATIONPrinted in U.S.A. Vol. 33, No. 3, pp. 154–155, 2005

This paper is available on line at http://www.bambed.org154

FIG. 1. Products of isoprene metabolism. Two minimaps on Isoprene Metabolism appear on my website, iubmb.org, one of which,Products of Isoprene Metabolism, is shown here. Its purpose is to illustrate something of the fascinating variety of well known productsthat can arise from multiples of this five carbon compound (C10, C15, C20, C30, and C40).

155