Biosynthesis of polyunsaturated fatty acids in the developing brain: II. Metabolic transformations of intracranially administered [3-14C] eicosatrienoic acid,evidence for lack of Δ8 desaturasedesaturase

[3-¹⁴C] Eicosatrienoic acid (Δ11,14,17) chemically synthesized from [1-¹⁴C] linolenic acid was injected intracranially into 14-day old rats and sacrificed 8 hr later. The analysis of brain fatty acids by radio-gas liquid chromatography before and after ozonolysis showed that the tetraene fraction consisted of a desaturated product, Δ5,11,17–20∶4, and its elongated product, Δ7,13,16,19–22∶4. Both of these products, with a combined total of 61% of the total radioactivity recovered in the tetraene fraction, contain a nonmethylene interrupted double bond system and, therefore, are unsuitable for further desaturation. The other two components, Δ6,9,12,15–18∶4 and Δ8,11,14,17–20∶4, must have been formed from Δ9,12,15–18∶3, formed by retroconversion of the starting material 20∶3, followed by desaturation and elongation. These results suggest a lack of Δ⁸ desaturase in the developing brain, leading to formation of Δ5,11,14,17–20∶4 rather than Δ8,11,14,17–20∶4. Howeve, the nonmethylene interrupted double bond isomer does not restrict chain elongation.     

Metabolism of linolenic acid in developing brain: I. Incorporation of radioactivity from 1-14C linolenic acid into brain fatty acids

Twelve-thirteen day old rats were given 1-¹⁴C linolenic acid by intraperitoneal injection. Fatty acids were isolated from the brains of animals sacrificed at the end of 8 and 48 hr and 15 and 45 days. Eight hr after the tracer, radioactivity was found neither in 18∶3 nor its endproduct, 22∶6, and palmitate was the most highly radioactive component. At longer intervals, 22∶6 seemed to retain much of the radioactivity, whereas palmitate showed a precipitous decline in radioactivity. Initial oxidation of linolenate and sparing of the linolenate complexed with polar lipids are discussed.     

Transient effects on microchannel electrokinetic filtering with an ion-permselective membrane

The electrokinetics and hydrodynamics in a hybrid microfluidic/nanofluidic pore network configuration and its effect on the concentration enrichment of charged analytes are described. A hydrogel microplug, photopolymerized in a microfluidic channel, with negative surface charge serves as a nanoporous membrane and dictates the electrokinetic behavior within the adjoining microchannel compartments. The nanoporous hydrogel with a mean pore size on the order of the electrical double layer thickness imparts ion-permselectivity (cation-selectivity) to the migration of ionic species which, under the influence of an applied electrical field, drives concentration polarization in bulk solution near the interfaces between the two microchannel compartments and the hydrogel-based nanopores. The concentration enrichment efficiency for charged analytes depends on this concentration polarization, which strongly affects the distribution of local electrical field strength. In addition, electroosmotic flow in the device plays a critical role in determining the location of the analyte enrichment zone. A theoretical model and simulations are presented to explain the interplay of concentration polarization and electroosmotic flow with respect to the observed concentration enrichment of negatively charged analytes at the cathodic hydrogel plug-microchannel solution interface.     

Metabolism of 1,2-(1-14C) dipalmitoyl phosphatidylcholine in the developing brain

Thirteen-day-old rats were divided into two groups; one group received 1,2-(1-¹⁴C) dipalmitoyl phosphatidylcholine and the other 1-¹⁴C palmitic acid in the form of an intraperitoneal injection. One half of the total number of rats in each group was sacrificed 24 hr after injection, and the other half was allowed to survive for 17 days after the injection. Radioactivity incorporated into brain and liver total lipids and into individiual polar lipid components of the brain was determined at both intervals. Phosphatidylcholine was isolated and partially deacylated with phospholipase A₂ fromCrotalus Admanteus venom. The ratio of radioactivity FA 2/FA 1 (fatty acid attached to 2 and 1 carbon of the glycerol moiety) 24 hr after the injection was 8.3, when the tracer was radioactive phosphatidylcholine, compared to only 0.7 when radioactive palmitate was injected. From this different labeling ratio and different pattern of labeling the polar lipid components, it was concluded that the radioactive phosphatidylcholine was not deacylated completely before being taken up directly into the brain. Possibilities are discussed to show that the observed radioactive ratio could result from direct uptake of intact phosphatidylcholine, with little or no restriction from the blood brain barrier system, followed by partial degradation by phospholipase A₁ in the brain itself. Presented in part at the AOCS Meeting, New Orleans, April 1973.     

Lipogenesis in the developing brain from intracranially administered [1-14C] acetate and [U-14C] glucose

Fifteen-day-old rats divided into two groups were given [1-¹⁴C]acetate or [U-¹⁴C] glucose by intracranial injection and were sacrificed after 1 hr. Analysis of lipids from the two groups showed differences in the incorporation of radioactivity in the polar lipids and cholesterol. Analysis of brain fatty acid showed that whereas radioactivity from acetate was incorporated into saturated, monoand polyunsaturated fatty acids, the radioactivity from [U-¹⁴C] glucose was found only in 16∶0, 18∶0, and 18∶1. No radioactivity was found in polyunsaturated fatty acids even after concentration of this fraction by AgNO₃:SiO₂ thin layer chromatographic method. This difference is discussed in hypothetical terms of nonhomogeneous acetyl CoA pool, formation of acetyl CoA from glucose exclusively inside the mitochondria, and activation of injected acetate to acetyl CoA.     

Roaming: Technologies for a Connected Society

We live in a truly connected society, at least in the Western world. The challenge now, therefore, isn't to provide connectivity but to retain it as users roam, potentially between unfamiliar and heterogeneous environments.     

Trans fatty acids: Positional specificity in brain lecithin

Fifteen-day-old rats were divided into three groups: one group received an intracerebral injection of 5 μ Ci of 9-trans, 12-trans [1-¹⁴C] octadecadienoic acid; the second group was given 5 μCi of the same compound plus an equal wt of nonradioactive allcis arachidonic acid; the third group was given 5 μCi of 9-trans [1-¹⁴C] octadecenoic acid. All animals were sacrificed 8 hr after injection. Glycerophosphocholine (GPC) was isolated and partically deacylated with phospholipase A₂ fromCrotalus Adamanteus venom. The results of this study were as follows: 1) aftert [1-¹⁴C] 18∶1 injection, there was twice as much radioactivity in the 1-position as in the 2-position; 2) whentt [1-¹⁴C] 18∶2 was injected, more than 90% of the total radioactivity was found in the 2-position; 3) followingtt[1-¹⁴C]-18∶2 +nonradioactive arachidonate injection, ca. 75% of the total radioactivity still remained in the 2-position; and 4) all of the injected [1-¹⁴C]-tracers showed evidence of undergoing β-oxidation to form acetyl-CoA, which was converted to radioactive palmitate. The possibility is discussed that the observed distribution pattern of the injected radioactive tracers may be attributed to tissue metabolic specificity. Ramifications of the deposition of dietarytrans fatty acids in the brain during the developmental stage of the central nervous system are also discussed.     

Role of oleic acid in the metabolism of essential fatty acids

Groups of young male guinea pigs were fed diets containing corn oil, coconut oil, coconut oil plus elaidic acid, and coconut oil plus oleic acid. The oleic acid-fed group showed signs of essential fatty acid deficiency after four weeks and severe signs after eight weeks. The elaidic acid-fed group did not show these symptoms. It is proposed that oleic acid competes competitively with linoleic acid as a substrate for the enzymes involved in linoleate transformations when only a very limited supply of linoleic acid is available to the animals and oleic acid is made available in relatively large amounts. A detailed analysis of the serum, liver, and adipose tissue lipid and a study of the incorporation of acetate-1-C¹⁴ into different lipids is presented. This paper is based on work supported in part by United States Public Health Grant No. HTS 5306 and by a grant from the Nutrition Foundation Inc., New York.     

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