Isoprenes
August, 2005
Derivatives of isoprenes, or isoprenoids, are abundant in nature, and exist in every living cell of every species.1Since isoprenes are derived from mevalonate, the synthesis of which is inhibited by statins, statin drugs interfere with the synthesis of all isoprene compounds.
The Chemistry of Isoprenes
The basic isoprene subunits are isopentenyl pyrophosphate and dimethyl allyl pyrophosphate, which are isomers of each other (meaning they have the same molecular formula and basic molecular structure, but the arrangements of the atoms within the molecules are slightly different).
Isopentenyl pyrophosphate and dimethyl allyl pyrophosphate are arranged in an alternating pattern to make isoprene chains, also called polyprenyl chains, of varying lengths. Two of the main polyprenyl chains are farnesyl, which is the 15-carbon chain, and geranylgeranyl, which is the 20-carbon chain.
Isoprenes in Other Species
Humans obtain important isoprene compounds from diet that are not synthesized by the human body. Vitamins A, E, K, and carotenes contain isoprene chains.
Many important medicinal compounds in plants are isoprenes. For example, the isoprenylated flavanoids kuwanon G and H were the first flavanoids discovered to lower blood pressure. Prenylphenols are isoprene compounds that have been found in medicinal herbs like licorice. 2
Importance of Isoprenes in the Human Body
Isoprenes are not only precursors to important compounds such as squalene, coenzyme Q10, and cholesterol, but many other important compounds in the body.
A series of polyisoprenoid alcohols of 14-24 isoprene units called "dolichols" are necessary for the biosynthesis of biologically important glycoproteins.3
Glycoproteins are proteins that have a sugar group attached to them. Most of the proteins synthesized in the edoplasmic reticulum, in fact, are glycoproteins. Dolichol helps anchor the sugar group to the endoplasmic reticulum while an enzyme attaches the protein to the sugar group. 4 The sugar groups on proteins play many important roles, including the identification of cells for cell communication.
Cell membranes contain many proteins used for hormone signaling, other forms of cell communication, transporting various substances across membranes, and maintaining the balance of electrical charges and minerals across the membrane.
Proteins that are anchored to a cell membrane by a lipid are either anchored by a prenyl (isoprene) group (farnesyl or geranylgeranyl) or a saturated fatty acid (usualy myristic but sometimes also palmitic acid.)5
Prenyl groups are important to the function of retinal proteins. For example, the specific prenyl group attached to a protein called "retinal transducin" determines its ability to change locations in response to light, which allows our eyes to adjust to changes in light and dark.
Although many isoprenes play positive functions in the body and all are necessary, geranylgeranyl pyrophosphate activates an enzyme called Rho that is part of the stress response. Chronic over-activation of Rho may contribute to atherosclerosis.
References
1. Rip et al., "Distribution, metabolism and function of dolichol and polyprenols," Prog Lipid Res. (1985) 24(40):269-309
2. Nomura, T., "Chemistry and biosynthesis of prenylflavanoids," Yakugaku Zasshi (2001) Jul; 121 (7): 535-56
3. Carroll et al., "Dolichol: function, metabolism, and accumulation in human tissues," Biochem Cell Biol. (1992) Jun; 70(6):382-4
4. Alberts et al., Molecular Biology of the Cell: Fourth Edition, (2002) New York: Garland Science, p. 702.
5. ibid, 595F.
6. Kassai, et al., "Farnesylation of Retinal Transducin Underlies Its Translocation during Light Adaptation," Neuron (2005) August 18(47): 529-539.