Further characterization of the heat-stable factor in the α-hydroxylation and oxidation of lignoceric acid in brain: Effect of acidic amino acids and hexose-phosphates on brain fatty acid metabolism

Abstract

Lignoceric acid and other very long-chain fatty acids are converted to α-hydroxy fatty acids and ceramide in brain. These fatty acids are also oxidized and produce glutamic acid and other water-soluble products. All of these metabolic conversions are catalyzed by a rat brain particulate fraction and require NADPH, heat-labile factor, and heat-stable factor. The heat-stable factor was prepared from calf cerebellum. Glucose 6-phosphate and N-acetylaspartic acid have previously been identified as active components of the heat-stable factor. We report in this manuscript that glutamic acid, glutamine, aspartic acid, and γ-aminobutyric acid as well as inorganic phosphate and adenosine nucleotides are also active components of the heat-stable factor. When the amino acids, glucose 6-phosphate, AMP, and phosphoric acid were combined, full activity of the heat-stable factor for the formation of cerebronate (by α-hydroxylation) and glutamate (presumably by β-oxidation) from lignoceric acid was recovered. The role of the acidic amino acids in the metabolic conversion of lignoceric acid in brain appears to be their conversion to the corresponding α-keto acids and then incorporation into the TCA cycle. Glucose 6-phosphate is also likely to be involved in the TCA cycle through the Emden-Meyerhof pathway. Inorganic phosphate and AMP seemingly are used to produce ATP. However, the addition of up to 20 m m ATP alone did not replace the heat-stable factor.