Fatty Acid Synthesis in the Developing Brain

Abstract

Extract: Fatty acid biosynthesis in the developing brain was studied. During development, total fatty acid synthesis was maximal at 15–16 days of age—a time of rapid myelination for this species. Results were expressed as mμmoles of ¹⁴C-labeled acetyl-CoA incroported into fatty acids per milligram of brain mitochondrial of microsomal protein, and as ¹⁴C-labeled malony-CoA incorporated per milligram of microsmal protein.

Elongation of saturated fatty acids by microsoms followed a similar development pattern. The peak incorporation of malaony-CoA into saturated fatty acids occurred at 15 days of age, while synthesis of polyunsaturated fatty acid did not change significantly with maturation. In the mitochondrial-acetyl-CoA system, elongation of potyunsaturated fatty acids was unchanged significantly with maturation. These result support the concept that chain elongation of fatty acids is directly ralated to myelination. The marked increase in the rate of elongation of saturated fatty acid by the micosmol fraction, occurring at this time, suggests that this system is involved in synthesis of myelin fatty acids.

Speculation: At the time myelination there is an increase in the activity of microsomes with resect to incroporating malony-CoA into saturated fatty asids, and into polyunsaturated fatty acids (20:2 and 20:4). This is unexpected because of the well established finding that in mature liver the microsomal fraction preferentially synthesizes polyunsaturated fatty acids, while the mitochondrial fraction forms saturated fatty acids. Polyunsaturated fatty acids constitute a relatively minor proportion of myelin fatty acids, and it is unlikely that the striking increase i microsomal activity observed at 15–16 days is necessary for their formation. It is possible that maturation changes the selectivity of the fatty acid synthesizing system, or that there are specificity differenced between the hepatic and cerebral microsomal chain elongation systems.

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