Neutrophils biosynthesize leukotoxin, 9, 10-epoxy-12-octadecenoate.

An epoxy derivative of linoleate, 9,10-epoxy-12-octadecenoate, was demonstrated to be biosynthesized by neutrophils from various sources such as canine and human blood, and guinea-pig peritonea. It was nominated as leukotoxin from its 'toxic' activity onto mitochondrial respiration. From the reaction mixture of leukocytes with linoleate, an isomer of leukotoxin, 12,13-epoxy-9-octadecenoate, and a 'non-toxic' hydroxy derivative of linoleate, 9-hydroxy-12-octadecenoate, were detected. Such a cascade reaction of linoleate by leukocytes was discussed. Biosynthesis of leukotoxin by neutrophils was substantially enhanced by the presence of calcium ion and calcium-ionophore, A23187. Neutrophils contained leukotoxin, ca. 7 f moles/cell, which was extractable by 60% ethanol, but little of the isomer.

Síntesis de éteres cíclicos prostanoides con actividad hematológica o inmunológica / Synthesis of prostandid cyclic ethers with hematological or inmunological activity

En este trabajo se presenta la síntesis de algunos éteres cíclicos prostanoides, análogos de la prostaciclina obtenidos partiendo del intermediario PGA2 (extraído del coral blando Plexura homomalla, recolectado en la costa note de Venezuela); conjuntamente con algunas pruebas farmacológicas preminares en el área de inmunología o hematología

Mechanism of inhibition of eukaryotic protein synthesis by trichothecene fungal toxins.

The 12,13-epoxytrichothecenes, a group of sesquiterpenoid fungal antibiotics, inhibit protein synthesis in eukaryotic cells but do not share a common mode of action. Trichodermin stabilizes polyribosomes, prevents their disaggregation by puromycin, and also prevents the release of nascent peptides from ribosomes by puromycin. Nivalenol, T-2 toxin, and verrucarin A cause rapid and almost quantitative breakdown of polyribosomes in H-HeLa cells, a process which is inhibited by anisomycin, cycloheximide, or trichodermin. Similar effects of trichodermin, nivalenol, and verrucarin A are also observed in yeast spheroplasts. We conclude that nivalenol, T-2 toxin, and verrucarin A are potent and highly selective inhibitors of polypeptide chain initiation in eukaryotes, whereas trichodermin inhibits chain elongation and (or) termination. We have compared the structural formulae of various trichothecenes and suggest that the presence of substituents on carbon-15 of the common trichothecene ring may be important in determining the precise modes of action of this group of compounds.

Pseudomonas oleovorans hydroxylation-epoxidation system: additional strain improvements.

The isolation and characterization of a strain of Pseudomonas oleovorans which epoxidates 1-octene at a rate nine times that of the original strain are described. In addition, it has been confirmed that a greater amount of the mono-epoxide product is formed from 1,7-octadiene than is formed from 1-octene. 1,7-octadiene will not support growth, but will induce the enzymes required for epoxidation.

Oxidation of 1-alkenes to 1,2-epoxyalkanes by Pseudomonas oleovorans.

Resting cells of Pseudomonas oleovorans PO-1R that had been grown on octane oxidized 1-alkenes containing 6 to 12 carbon atoms and 1,7-octadiene to their corresponding 1,2-epoxides. The microorganism was capable of growing on 1-octene but not on 1,7-octadiene as a sole carbon source. The optimal temperature, pH, and 1-octene concentration for 1,2-epoxyoctane production by the resting cells were 34 to 40 C, pH 7 to 8, and 1.5 mg of 1-octene per ml, respectively. Epoxide concentration reached a maximum after 150 min of incubation and subsequently declined. In the absence of 1-octene, the epoxide was metabolized readily by the resting cells. The amount of 1,2-epoxyoctane produced was dependent on the initial cell concentration. With larger cell populations, the amount of epoxide present after 60 min of incubation was less than the amount observed at lower population densities after the same time period. This relationship was attributed to the rapid depletion of 1-octene at high biomass concentrations and the resultant early initiation of epoxide degradation by the resting cells.

Octene epoxidation by a cold-stable alkane-oxidizing isolate of Pseudomonas oleovorans.

The isolation of an alkane-oxidizing strain of Pseudomonas oleovorans which maintains its viability at 5 C is described. This strain epoxidates 1-octene at a rate five times that of the parent strain. The most efficient substrates for induction of the epoxidase are C(7), C(8), and C(9), although C(5) to C(12) also serve as growth substrates and inducers. The greater rate may be attributed to an enhanced general stability of the cells as opposed to a modification of the enzyme system involved.