Different Fatty Acids Compete with Arachidonic Acid for Binding to the Allosteric or Catalytic Subunits of Cyclooxygenases to Regulate Prostanoid Synthesis.

Prostaglandin endoperoxide H synthases (PGHSs), also called cyclooxygenases (COXs), convert arachidonic acid (AA) to PGH2. PGHS-1 and PGHS-2 are conformational heterodimers, each composed of an (Eallo) and a catalytic (Ecat) monomer. Previous studies suggested that the binding to Eallo of saturated or monounsaturated fatty acids (FAs) that are not COX substrates differentially regulate PGHS-1 versus PGHS-2.

Epoxy acetylenic lipids: their analogues and derivatives.

Currently, approximately 250 natural acetylenic epoxy structures are known. The present review describes research concerning biologically active epoxy acetylenic lipids and related compounds isolated from different sources. Intensive searches for new classes of pharmacologically potent agents produced by living organisms have resulted in the discovery of dozens of such compounds that possess high anticancer, cytotoxic, antibacterial, antiviral, and other activities.

Bioactive acetylenic metabolites.

This article focuses on anticancer, and other biological activities of acetylenic metabolites obtained from plants and fungi. Acetylenic compounds belong to a class of molecules containing triple bond(s). Naturally occurring acetylenics are of particular interest since many of them display important biological activities and possess antitumor, antibacterial, antimicrobial, antifungal, and immunosuppressive properties.

Major urinary metabolites of 6-keto-prostaglandin F2α in mice.

Western diets are enriched in omega-6 vs. omega-3 fatty acids, and a shift in this balance toward omega-3 fatty acids may have health benefits. There is limited information about the catabolism of 3-series prostaglandins (PG) formed from eicosapentaenoic acid (EPA), a fish oil omega-3 fatty acid that becomes elevated in tissues following fish oil consumption.

Human cyclooxygenase-1 activity and its responses to COX inhibitors are allosterically regulated by nonsubstrate fatty acids.

Recombinant human prostaglandin endoperoxide H synthase-1 (huPGHS-1) was characterized. huPGHS-1 has a single high-affinity heme binding site per dimer and exhibits maximal cyclooxygenase (COX) activity with one heme per dimer. Thus, huPGHS-1 functions as a conformational heterodimer having a catalytic monomer (E(cat)) with a bound heme and an allosteric monomer (E(allo)) lacking heme.

Fluorescent n-3 and n-6 very long chain polyunsaturated fatty acids: three-photon imaging in living cells expressing liver fatty acid-binding protein.

Despite the considerable beneficial effects of n-3 and n-6 very long chain polyunsaturated fatty acids (VLC-PUFAs), very little is known about the factors that regulate their uptake and intracellular distribution in living cells. This issue was addressed in cells expressing liver-type fatty acid-binding protein (L-FABP) by real time multiphoton laser scanning microscopy of novel fluorescent VLC-PUFAs containing a conjugated tetraene fluorophore near the carboxyl group and natural methylene-interrupted n-3 or n-6 grouping. The fluorescent VLC-PUFAs mimicked many properties of their native nonfluorescent counterparts, including uptake, distribution, and metabolism in living cells.

Cyclooxygenase Allosterism, Fatty Acid-mediated Cross-talk between Monomers of Cyclooxygenase Homodimers.

Prostaglandin endoperoxide H synthases (PGHSs) 1 and 2, also known as cyclooxygenases (COXs), catalyze the oxygenation of arachidonic acid (AA) in the committed step in prostaglandin (PG) biosynthesis. PGHSs are homodimers that display half of sites COX activity with AA; thus, PGHSs function as conformational heterodimers. Here we show that, during catalysis, fatty acids (FAs) are bound at both COX sites of a PGHS-2 dimer.

Chemical C2-elongation of polyunsaturated fatty acids.

Three fatty acids were synthesized from commercially available alpha-linolenic, stearidonic and eicosapentaenoic acids by C2-elongation using a four step preparative technique. The parent fatty acid methyl esters were reduced to alcohols with LiAlH(4), converted to bromides by treatment with triphenylphosphine dibromide, coupled with a lithiated C2-elongation block--2,4,4-trimethyl-2-oxazoline--to form the corresponding 2,2-dimethyloxazolines of C2-elongated fatty acids, and finally, converted to the target polyunsaturated fatty acids by acidic alcoholysis. Yields of more than 60% were achieved on a gram scale.

Synthesis of four isomers of parinaric acid.

A simple and reliable method for synthesizing four isomers of parinaric acid from alpha-linolenic acid (ALA) in high yields is described. The methylene-interrupted, cis triene system (1,4,7-octatriene) of ALA and common to other naturally occurring polyunsaturated fatty acids was transformed to a conjugated tetraene system (1,3,5,7-octatetraene). The synthesis involves bromination of ALA using 0.

Synthesis of long chain n-3 and n-6 fatty acids having a photoactive conjugated tetraene group.

Fatty acids of the n-3 and n-6 families containing a photoactive conjugated tetraene group near the carboxylate were prepared from several naturally occurring fatty acids by sequential iodolactonization and treatment with excess 1,8-diazabicyclo[5.4.0]undec-7-ene.

A procedure for preparing oxazolines of highly unsaturated fatty acids to determine double bond positions by mass spectrometry.

A convenient, mild, reliable method has been developed for preparing oxazolines of fatty acids and for using these derivatives to determine double bond locations in long-chain polyunsaturated and polyconjugated fatty acids. Fatty acyl mixed anhydrides are prepared using isobutylchloroformate and then converted to their ethanolamides by treatment with ethanolamine. Ethanolamides are subsequently cyclized to the corresponding oxazolines in >or=85% yields by treatment with trifluoroacetic anhydride under mild conditions (>50 degrees for 30-60 min).