The Company
Lipidox is a newly established Swedish company having its roots in the Karolinska Institute, Stockholm. We provide a series of unusual fatty acids for use as standards and substrates in biomedical research. We also carry out custom synthesis of unlabeled and deuterium-labeled fatty acids including polyunsaturated, branched chain and oxygenated structures.
Fatty acids
Fatty acids are organic compounds having the general formula R-COOH. Structural and geometrical isomerism of the alkyl chain can theoretically lead to myriads of different structures. However, fatty acids from biological sources show relatively modest structural variation, a fact that can be ascribed to the specificities of the biosynthetic enzymes. Thus, unbranched acyl chains having an even number of carbon atoms are the rule, a consequence of the mechanism of biological fatty acid synthesis by successive two-carbon elongations starting from acetyl-CoA. Unsaturated fatty acids, divided in monounsaturated ones having one double bond and polyunsaturated having two or more double bonds, likewise show limited structural variation because of the specificities of the desaturase enzymes involved. Such enzymes most often introduce Z-configured double bonds at the ω3, ω6 or ω9 positions counted from the methyl end, or homoallylically to an existing double bond in the carboxyl end. Commonly occurring polyunsaturated fatty acids of the ω3, ω6 or ω9 families possess two or more copies of the Z-configured element -CH=CH-CH2- and have at least one bisallylic methylene group, -CH=CH-CH2-CH=CH-. It is the lowered carbon-hydrogen bond dissociation energy of this bisallylic methylene that makes polyunsaturated fatty acids susceptible to autoxidation and also allows enzymatic conversions by e.g. lipoxygenases, cyclooxygenases and conjugases.
Deviations from the above outlined rules, or secondary transformations of existing fatty acids, lead to the formation of various uncommon fatty acids in animals, plants and bacteria. Thus, fatty acids having an odd number of carbons can be produced by α-oxidation pathways by which existing acyl chains are shortened by one carbon atom. Branches may be introduced by alkylation of unsaturated acyl chains, such as the formation of 10-methylstearic acid (tuberculostearic acid) in tubercle bacilli by methylation of oleate by S-adenosylmethionine. Certain unorthodox fatty acid desaturases introduce double bonds in uncommon positions, e.g. the 5(Z) double bond of 5(Z),9(Z)-octadecadienoic acid (taxoleic acid), the 5(E) double bond of 5(E),9(Z),12(Z)-octadecatrienoic acid (columbinic acid), and the 6(Z) double bond of 6(Z)-hexadecenoic acid (sapienic acid). Furthermore, the recently studied conjugase type of desaturases catalyzes the dehydrogenation of polyunsaturated fatty acids into conjugated trienoic and tetraenoic acids such as α-eleostearic, punicic and parinaric acids.
Lipidox takes special interest in the isolation of uncommon fatty acids from natural sources and also applies synthetic methods for modification of existing fatty acids. In this way we can provide a collection of unusual fatty acids and methyl esters, many of which are not available from other commercial sources.
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Prostaglandin H2 (PGH2) is formed from arachidonic acid in the presence of prostaglandin endoperoxide synthases. The compound was originally detected as an intermediate in the biosynthesis of prostaglandin E2 in a preparation of the sheep vesicular gland (1) and subsequently isolated in pure form and characterized (2). Not unexpectedly, the endoperoxide turned out to be chemically unstable (half life time, about 5 min at 37o in aqueous buffers). Spontaenous degradation of PGH2 in buffer generates mainly a mixture of prostaglandins E2 and D2 (ratio about 4:1); interestingly, this ratio is reversed in the presence of serum albumin (3). Several enzymes including prostaglandin E and D synthases, thromboxane synthase and prostaglandin I synthase catalyze the conversion of PGH2 into specific, biologically active eicosanoids. Aspirin and other non-steroidal antiinflammatory drugs block prostaglandin biosynthesis (4) by exerting an inhibitory effect on prostaglandin endoperoxide synthases. Intake of aspirin leads to reduced formation of thromboxane A2 in circulating blood platelets and provides a certain protection against myocardial infarction and stroke, especially in patients with documented cardio- or cerebrovascular disease. Current interest in PGH2 is focussed on its role as a substrate for prostaglandin E synthases (5), and on the design of specific inhibitors of this class of enzymes.
Prostaglandin H2 (O-2004-1) was discovered at the Karolinska Institutet and accordingly Lipidox has good experience in the isolation, purification and handling of this unstable eicosanoid. Also available is the 8,11,14-eicosatrienoic acid-derived endoperoxide, prostaglandin H1 (O-2004-2).
1. Hamberg, M. and Samuelsson, B. (1973) Proc. Natl. Acad. Sci. USA 70, 899-903
2. Hamberg, M. et al. (1974) Proc. Natl. Acad. Sci. USA 71, 345-349
3. Hamberg, M. and Fredholm, B.B. (1976) Biochim. Biophys. Acta 431, 189-193
4. Vane, J.R. (1971) Nature New Biol 231, 232-235
5. Jakobsson, P.J. et al. (1999) Proc. Natl. Acad. Sci. USA 96, 7220-7225
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