Synthesis of alkyl-ether glycerophospholipids in rat glomerular mesangial cells: evidence for alkyldihydroxyacetone phosphate synthase activity.

We studied the ability of rat glomerular mesangial cells and their microsomal fractions to incorporate 1-[14C]hexadecanol to glycerophospholipids via an O-alkyl ether linkage and assessed the presence and activity of the required enzyme: alkyl-dihydroxy acetone phosphate synthase. Suspensions of cultured mesangial cells incorporated 1-[14C]hexadecanol to the phosphatidyl ethanolamine and phosphatidyl choline lipid pools, via a bond resistant to acid and base hydrolysis. When cell homogenates or microsomal fractions were incubated with palmitoyl-DHAP and 1-[14C]hexadecanol, alkyl-DHAP and 1-O-alkyl glycerol were formed (alkyl:hexadecyl). The activity of the enzyme responsible for the O-alkyl product formation was calculated to be 2.5 +/- 0.3 and 544 +/- 50 pmoles/min/mg protein for mesangial cell homogenates and mesangial cell microsomes, respectively. These observations provide evidence that mesangial cells may elaborate either linked lipid precursors de novo for the biosynthesis of O-alkyl glycerophospholipids.

The thrombin-dependent enrichment of alkenylacyl ethanolamine phosphoglyceride with [14C]eicosapentaenoic and [3H]arachidonic acids in prelabelled human platelets.

The thrombin-dependent enrichment of alkenylacyl ethanolamine phosphoglyceride in [14C]eicosapentaenoic acid [( 14C]EPA) was demonstrated and compared with [3H]arachidonic acid [( 3H]AA) following the simultaneous prelabelling of individual human platelet phospholipids with these two fatty acids. The alkenylacyl, diacyl, and alkylacyl classes of ethanolamine phosphoglycerides (PE) were separated by thin-layer chromatography as their acetylated derivatives after hydrolysis of the parent phospholipid with phospholipase C. The ratios of [3H]/[14C] for the increased radioactivity appearing in alkenylacyl PE following 60 and 120 s of thrombin stimulation were the same as the corresponding ratio (2.0) found in the choline phosphoglycerides (PC) from control (unstimulated) platelets. These results suggest no significant selectivity between EPA and AA in the thrombin-stimulated transfer of these fatty acids from diacyl PC to alkenylacyl PE. The present findings may possibly bear some relevance to the altered platelet reactivity and (or) decreased thromboxane A2 formation observed in human subjects following the ingestion of marine lipid containing EPA.

Ferensimycins A and B. Two polyether antibiotics. Taxonomy, fermentation, isolation, characterization and structural studies.

Ferensimycin A* (I), C34H59O10Na, mp 133 approximately 135 degrees C, and ferensimycin B** (II), C35H61O10Na, mp 143 approximately 145 degrees C, were isolated as their sodium salts from the fermentation broth of Streptomyces sp. No. 5057, a strain similar to Streptomyces myxogenes Shomura et al. The physicochemical data of I and II showed that they are both closely related congeners of lysocellin (III). Ferensimycins A and B exhibit activity against Gram-positive bacteria and are effective in the treatment of coccidiosis of fowl.

Studies on the ionophorous antibiotics. XXIV. Leuseramycin, a new polyether antibiotic produced by Streptomyces hygroscopicus.

A new antibiotic leuseramycin has been isolated from the cultured mycelium of the strain of Streptomyces hygroscopicus TM-531. Physicochemical data, in particular those of 1H- and 13C-NMR spectra, revealed that leuseramycin is closely related to dianemycin in its structure, the former having a methyl group in place of the hydroxymethyl group at C-30. It is active against Gram-positive bacteria, some phytopathogenic fungi and some protozoa.

Studies on the ionophorous antibiotics. XXV. The assignments of the 13C-NMR spectra of dianemycin and lenoremycin.

All the resonances observed in the 13C-NMR spectra of polyether antibiotics, dianemycin and lenoremycin (Ro 21-6150) have been assigned by the aid of selective proton decoupling experiments, T1 value measurements and biosynthetic methods as well as comparison to model compounds such as monensin, nigericin, etheromycin and carriomycin.

Synthesis and content of ether-linked glycerophospholipids in the harderian gland of rabbits.

Although harderian glands are rich in neutral glycerolipids with ether bonds, less than 20% of the choline glycerophospholipids have ether bonds in the white and pink portions of the adult rabbit harderian gland. Only 6% of these are plasmalogens while 94% are alkylacyl glycerophosphocholines. The ethanolamine glycerophospholipids include 37% with ether bonds in both white and pink portions. In the white portion 96% are plasmalogens but only 19% are plasmalogens in the pink portion. The microsomal ethanolaminephosphotransferase (EC 2.7.8.1) is more active with diacylglycerols than with alkylacylglycerols. The microsomal cholinephosphotransferase (EC 2.7.8.2) is equally active with both diradylglycerols. Particularly with microsomes from the pink portion, the apparent Km values for CDPethanolamine and CDPcholine are ower in the presence of alkylacylglycerols than in the presence of diacylglycerols. The incorporation of radioactivity from CDP[14C]ethanolamine and CDP[14C]choline into ethanolamine and choline plasmalogens was increased several-fold by addition of alkylacylglycerols but was not increased substantially by addition of diacylglycerols.

Ionomycin, a new polyether antibiotic.

Ionomycin, a new polyether antibiotic with a high affinity for calcium ions, is obtained in pure form from fermentation broths of Streptomyces conglobatus sp. nov. Trejo by solvent extraction. It is unique amongst known polyether antibiotics in that it has a UV absorption maximum at 300 nm. thereby distinguishing it from other antibiotics of its class. The Ca salt has the molecular formula C41H70O9Ca. Ionomycin is a narrow spectrum antibiotic being active against Gram-positive bacteria.

Noboritomycins A and B, new polyether antibiotics.

Noboritomycins A and B, two new polycyclic ionophoric polyethers were isolated from a strain of Streptomyces noboritoensis. The crystal structure and absolute configuration of noboritomycin A were established by X-ray analysis of its silver salt C43/63O14Ag. Noboritomycin A is the first metabolic polyether possessing two carboxylic acid functions on the carbon backbone (C-31), namely a free acid and an additional carboxylic acid ethylester group. An unusual spiroketal system as well as a salicylic acid chromophore represent further remarkable elements. Noboritomycin A shows in this respect a structural relationship to salinomycin and lasalocid respectively. Comparison of physico-chemical data, in particular the interpretation of the 1H- and 13C-NMR spectra, revealed that noboritomycins A and B are structurally closely related, noboritomycin B carrying an ethyl substituent on the aromatic ring in the place of a methyl group present in noboritomycin A. Both metabolites exhibit activity against Gram-positive bacteria and against Eimeria tenella (chicken coccidiosis).

Antibiotic DE-3936, a polyether antibiotic identical with lonomycin. Taxonomy, fermentation, isolation and characterization.

Antibiotic DE-3936 was isolated from the fermentation broth of a streptomycete No. 9735-1, which is identified as a strain of Streptomyces hygroscopicus. The antibiotic is a hydrophobic compound having the molecular formula of of C44H75O14Na and is active against Gram-positive bacteria, mycobacteria, mycoplasma and protozoa, especially coccidia. Its chemical and biological properties indicate that antibiotic DE-3936 belongs to the group of polyether antibiotics and is identical with lonomycin.

Emericid, a new polyether antibiotic from Streptomyces hygroscopicus (DS 24 367).

Emericid is a new polyether polycyclic ionophore antibiotic excreted by Streptomyces hygroscopicus (DS 24 367). Active in vitro against Gram-positive bacteria, it is ineffective in vivo. At a 0.006-0.02% level in the diet it protects chickens and rabbits against coccidiosis.

The enzymic conversion of linoleic acid into 9-(nona-1',3'-dienoxy)non-8-enoic acid, a novel unsaturated ether derivative isolated from homogenates of Solanum tuberosum tubers.

1. A major component of the lipids in aqueous (pH7.5) homogenates of tuber tissue from Solanum tuberosum was isolated and characterized as 9-(nona-1',3'-dienoxy)non-8-enoic acid. 2. This novel unsaturated ether fatty acid derivative, which contains a butadienylvinyl ether function, has the structure: [Formula: see text] and is formed from linoleic acid by a sequence of enzymic reactions. 3. A precursor of the unsaturated ether derivative is 9-d-hydroperoxyoctadeca-10,12-dienoic acid, formed by the action of S. tuberosum lipoxygenase on linoleic acid. 4. An enzyme that converts the fatty acid hydroperoxide into the unsaturated ether derivative was isolated from S. tuberosum. The pH optimum of this enzyme is approx. 9, although the overall conversion of linoleic acid into the ether derivative is maximal at pH7.5. 5. An unusual feature of this pathway is the insertion of an oxygen atom into the alkyl chain of a fatty acid. 6. This novel mechanism may play a role in the breakdown of polyunsaturated fatty acids to volatile products in plants.