Q: Hello lipidox,
How do you define oxylipin?
A: "Oxylipin" is a collective name for oxygenated fatty acids occurring in animals, plants and fungi, in which the extra oxygen function is derived from molecular oxygen. This means that biosyntheis of oxylipins can involve either dioxygenase, monooxygenase or peroxygenase types of enzymes. Also the nonenzymatically formed "phytoprostanes" in plants and "isoprostanes" in animals are oxylipins. The animal "eicosanoids" can be regarded as a subdivision of oxylipins in which the members are derived from 20-carbon fatty acids. Jasmonic acid and prostaglandins are typical oxylipins occurring in plants and animals, respectively. See also http://en.wikipedia.org/wiki/Oxylipin
Q: You say that sciadonic acid does not form prostaglandins. What about
other arachidonic acid analogs?
A: Sciadonic acid can be regarded as the 8,9-dihydro analog of arachidonic acid (AA) and can not form prostaglandins or leukotrienes, however, it can be converted by 15-lipoxygenase to a hydroperoxide. The 5,6-dihydro analog of AA is identical with dihomo-gamma-linolenic acid (biological precursor of AA). This compound can be converted to prostaglandins but not to leukotrienes. It is a substrate for 15-lipoxygenase. The 11,12-dihydro derivative of AA can form neither prostaglandins nor leukotrienes, however, its can be oxygenated by 5-lipoxygenase to a 5-hydroperoxide. Finally the 14,15-dihydro analog av AA is the socalled "Mead acid", which accumulates in animals deficient in essential fatty acids. This compound can form leukotrienes of the A and C types but not the B type (apparently due to the specificity of leukotriene A4 hydrolase). Mead acid can not form prostaglandins.
Q: I read about the Leukotoxins. There is no mention about stereochemistry. What is the absolute config of natural Leukotoxin?
A: As far as we know, this has not been investigated. The epoxide group in leukotoxins is cis-configured but data on enantiomers seem to be lacking. Indeed this should be studied, partly in view of the role of epoxide hydrolases which can be expected to act stereospecifically. Of course, concerning the arachidonic acid derived epoxides ("EETs") a lot of stereochemistry has been done; see e.g. Karara, A. et al. (1989) J. Biol. Chem. 264, 19822-19827.
Q: What are isoprostanes and phytoprostanes?
A: These are names of nonenzymatically produced prostaglandin-like compounds in animals and plants. The first report of nonezymatical formation of a prostaglandin was by D.H. Nugteren et al. in 1967 (Recl. Trav. Chim. Pays-Bas 86, 1237), and later J.D. Morrow and L.J. Roberts studied in detail the various prostaglandins, "isoprostanes", which are produced nonenzymatically in animals from arachidonic acid and other polyunsaturated fatty acids (for review, see Milne, G.L. et al. (2008) J. Biol. Chem. 283, 15533-15537). M.J. Mueller discovered an analogous series of compounds, termed "phytoprostanes", which are formed nonenzymatically from linolenic acid in plants (for review, see Thoma, I. et al. (2004) Chem. Phys. Lipids 128, 135-148). A comprehensive review of nonenzymatically formed oxylipins appeared recently, see Jahn, U. et al. (2008) Angew. Chem. 47, 5894-5955.
Many isoprostane and phytoprostane oxylipins are biologically active. Some of them possess a,b-unsaturated carbonyl structures and can serve as 'reactive electrophile species', RES.
Q: Please explain about the jasmonic acids. What is "natural" jasmonic acid?
A: Jasmonic acid exists in a number of stereoisomeric forms. "Natural" jasmonic acid has the 3(R),7(S) configuration and is formed from 9(S),13(S)-12-oxophytodienoic acid (the stereochemistry of which is dictated by the specificity of its biosynthetic enzyme, allene oxide cyclase).
Jasmonic acid has a tendency to epimerization at C-7 because of enolization of the ring carbonyl, especially under alkaline conditions or at elevated temperature. This results in equilibrium mixtures containing only about 6% of the natural 3(R),7(S) form and 94% of the more stable 3(R),7(R) form. In the original studies on the isolation and structure determination of jasmonic from the 1960s, the more stable, but artifically generated, 3(R),7(R) form was used and referred to as "jasmonic acid" or "(-)-jasmonic acid".
The importance of the natural 3(R),7(S) form, referred to as "(+)-7-iso-jasmonic acid", is becoming increasingly clear. For example, this is the stereoisomer responsible for the jasmine fragrance of methyl jasmonate mixtures, and this is the stereoisomer of jasmonic acid-isoleucine conjugates which activates the plant COI1 receptor (Fonseca et al. (2009) Nature Chem. Biol. 5, 344-350).
Q (followup on jasmonic acid): Thanks, however, I still don´t quite get it. Formula of "natural" jasmonic acid sometimes show the two side chains pointing upwards, somtimes downwards?
A: You are right, this can be a source of confusion. The explaination is that two different projections can be drawn of the cyclopentanone ring. If the ring is drawn with the ring carbonyl on the lower side (preferred by us), then both side chains point downwards (a-oriented) in natural jasmonic acid. But if the carbonyl is on the upper side (rotation of the ring 180C), then the two side chains will point upwards (b-oriented).