Non-cyclooxygenase prostaglandin synthesis in the sea whip coral, Plexaura homomalla: an 8(R)-lipoxygenase pathway leads to formation of an alpha-ketol and a Racemic prostanoid
Plexaura homomalla is a rich natural source of prostaglandins and recent evidence suggest the prostaglandin biosynthesis could occur through a lipoxygenase pathway. We have investigated the metabolism of arachidonic acid in homogenates and acetone powders of the fresh frozen coral. The biosynthesis of natural prostaglandins was not detected. However, we find a prominent 8(R)-lipoxygenase pathway leading to an alpha-ketol, characterized by high pressure liquid chromatography, gas chromatography-mass spectrometry, and NMR as 8-hydroxy, 9-keto-eicosa-5Z, 11Z, 14Z-trienoic acid, and a prostaglandin A-like cyclopentenone identified as 9-oxo-(8, 12-cis)-prosta-5Z, 10, 14Z-trienoic acid. These reactions appear analogous to the transformation of linolenic acid hydroperoxide by isomerase and cyclase of corn and flaxseed. From analysis of the absolute configurations of the coral products, and from additional stable isotope labeling experiments in H/sub 2//sup 18/O and D/sub 2/O, we deduce that both compounds arise via conversion of 8(R)-HPETE to an 8(R), 9-allene oxide, 8R,9-oxido-eicosa-5Z, 9, 11Z, 14Z-tetraenoic acid. This unstable intermediate undergoes hydrolysis to form the alpha-ketol or cyclization to give the cyclopentenone. Significantly, we find that the prostaglandin-like product is a racemic mixture of cis side chain enantiomers, pointing to its nonenzymatic origin from the allene oxide. The alpha-ketol is formed with partial racemization and inversion of configuration, also compatible with formation in a nonenzymatic reaction. We conclude that the isomerase and cyclase reactions may merely reflect nonenzymatic breakdown of the enzymatically formed allene oxide.
- Research Organization:
- Vanderbilt Univ., Nashville, TN
- OSTI ID:
- 5726570
- Journal Information:
- J. Biol. Chem.; (United States), Vol. 262:33
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
ARACHIDONIC ACID
METABOLISM
OXYGENASES
ENZYME ACTIVITY
PROSTAGLANDINS
BIOSYNTHESIS
BIOLOGICAL PATHWAYS
CORALS
DEUTERIUM
GAS CHROMATOGRAPHY
HOMOGENATES
LIQUID COLUMN CHROMATOGRAPHY
MASS SPECTROSCOPY
OXYGEN 18
TRACER TECHNIQUES
WATER
CARBOXYLIC ACIDS
CHROMATOGRAPHY
CNIDARIA
ENZYMES
EVEN-EVEN NUCLEI
HYDROGEN COMPOUNDS
HYDROGEN ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
MONOCARBOXYLIC ACIDS
NUCLEI
ODD-ODD NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
OXIDOREDUCTASES
OXYGEN COMPOUNDS
OXYGEN ISOTOPES
SEPARATION PROCESSES
SPECTROSCOPY
STABLE ISOTOPES
SYNTHESIS
550201* - Biochemistry- Tracer Techniques