Polyunsaturated-fatty-acid oxidation in Hydra: regioselectivity, substrate-dependent enantioselectivity and possible biological role.
A novel and abundant lipoxygenase-like activity converting cis-eicosa-5,8,11,14-tetraenoic acid (arachidonic acid) into (11R)-hydroxyeicosatetraenoic acid has been recently described in homogenates of the freshwater hydrozoan Hydra vulgaris. In this study, other substrates for this enzyme were selected from the polyunsaturated fatty acids (PUFAs) present in H. vulgaris, and the chemical natures of the hydroperoxy and hydroxy derivatives produced, as well as the activity of some of the latter on hydroid tentacle regeneration, were investigated. The highest conversion among C20 fatty acids was observed for arachidonic acid, and among C18 fatty acids for cis-octadeca-9,12,15- and cis-octadeca-6,9,12-trienoic (alpha- and gamma-linolenic) acids. Cis double bonds on the 10th carbon atom from the aliphatic end of the substrate (e.g. C-9, C-11 and C-13 respectively in C18, C20 and C22 PUFAs) were regiospecifically peroxidized. Conversely, trans-octadeca-9,12-dienoic (linoelaidic) acid was not a substrate for lipoxygenase activity. Enantioselectivity of lipoxygenation depended on the degree of unsaturation of the substrate, with the amount of the R enantiomer increasing when passing, for example, from cis-eicosa-11,14-dienoic to cis-eicosa-5,8,11,14,17-pentaenoic acid. Regiospecific formation of keto acids was observed only when incubating C18 PUFAs. Commercially available hydroxyacids corresponding to the reaction products of some of the most abundant H. vulgaris PUFAs were tested for effects on Hydra tentacle regeneration. An enhancement of average tentacle number, in a fashion depending on the stereochemistry and on the number of double bonds, was found for two compounds, thus suggesting for the 11-lipoxygenase-like enzyme a role in the production of metabolites potentially active in the control of hydroid regenerative processes.
Di Marzo
V
V
Istituto per la Chimica di Molecole di Interesse Biologico, C.N.R., Naples, Italy.
Gianfrani
C
C
De Petrocellis
L
L
Milone
A
A
Cimino
G
G
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D006829:Hydra / Q000378:metabolism* / Q000502:physiology; D008084:Lipoxygenase / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D010084:Oxidation-Reduction; D012038:Regeneration; D013237:Stereoisomerism; D013379:Substrate Specificity
D005231:Fatty Acids, Unsaturated; D008084:Lipoxygenase