Synthesis of Cholesterol and Fatty Acids in Fractions of Peripheral Nerve*†

Hughes, Ann H.; Eliasson, S

doi:10.1172/jci104009

Cited by 6 publications

(2 citation statements)

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“…In animals myelin has been demonstrated to be in a dynamic state of turnover, and certain lipids (inositol phosphatide and lecithin) are known to turn over more rapidly than others (9,10). It has been suggested that the formation and integrity of myelin is dependent upon the quantity of specific fatty acids available (12,28). The present study has shown that in the presence of a metabolic intermediate (propionic acid) which is known to accumulate in pernicious anemia, there is a decrease in net synthesis of normal fatty acids in neural tissue.…”

Section: Discussionmentioning

confidence: 99%

“…Since folic acid does not improve the neuropathy and since there are only two reactions known to require B12 in man, it seems attractive to suppose that the neurological lesion in B12 deficiency is associated with abnormal propionate metabolism. It is known that myelin lipids turnover at a significant rate (9)(10)(11) and that myelin renewal requires normal fatty acid synthesis (12 (13). Conceivably, deranged fatty acid synthesis could result in abnormal myelin which in turn might be an accompaniment of the neuropathy of pernicious anemia.…”

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confidence: 99%

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Abnormal Fatty Acid Metabolism in Peripheral Nerves of Patients with Pernicious Anemia

Frenkel

1973

J. Clin. Invest.

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A B S T R A C T Fatty acid synthesis from radiopropionate was evaluated. in sural nerve biopsy slices from five normal controls and nine patients with pernicious anemia.The nerves were incubated in ["4C]propionate, the lipids were extracted, and the fatty acid methyl esters were chromatographed by gas-liquid chromatography. In the normal nerves the radiolabel was found primarily in short chain (C12 and C14) fatty acids. The nerves from pernicious anemia patients showed two fatty acids peaks that were not discernible in the normal nerves, and these fatty acids had retention times intermediate to those of myristic (C14.0) and palmitic (C160) acids and palmitoleic (C16 1) and stearic (C18 0) acids, respectively. These two peaks (a C15 and C17 fatty acid) contained the bulk of the radioactivity recovered in the fatty acid fraction after incubation with ['4C]propionate. Catalytic reduction and rechromatography failed to alter the retention time of these compounds suggesting that they are not unsaturated fatty acids. The nerves from the pernicious anemia patients had a decrease in the mean content of normal fatty acids when compared with the nerves from control patients as well as a decrease in the mean synthesis of normal fatty acids as estimated by isotope incorporation after incubation with ["C]propionate or 'H20. Analysis of myelin isolated from the nerves indicated that the changes at least in part were in that fraction.A portion of this material was presented at the 63rd An- (Fig. 1) (4). The source of folate in this reaction is the storage form of folate, N -methyltetrahydrofolic acid. The clinical expression of vitamin B12 deficiency, via interference with this pathway, is based upon the need of B12 as a coenzyme for the methyltransferase reaction. Thus B12 deficiency results in a "trapping" of this storage folate reducing available active folate coenzyme forms. Since active folate is required in the conversion of deoxyuridylic acid to thymidylic acid, deprivation interferes with the pyrimidine biosynthetic pathway of deoxyribonucleic acid producing the classic megaloblastic changes seen in B12 deficiency (5-7). As would be anticipated folic acid bypasses this alteration and effectively repairs the defect even in the continued absence of vitamin B12 (Fig. 1).The second biochemical pathway that is affected by vitamin B12 deficiency is that responsible for the metabo-1,-1bbrcviations used in this tapier: GLC, gas-li(quid chromatograplly; PA, pernicious anemia.

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