Fatty acid synthesis in the developing brain.

The study of biochemical aspects of brain metabolism is very complex because brain tissue is composed of different cell types. The two major cell types are neurones and oligodendroglia. These two cell types have differing roles but are very closely associated with normal brain development and function. Oligodendroglia are responsible
for the synthesis and maintenance of the myelin membrane. In the developing brain, the myelin membrane is formed during a very short period of time. The aims of this study are (i) to investigate age-dependent changes in the activity of the lipogenic enzymes, fatty acid synthetase and palmitoyl-CoA synthetase which are
intimately involved in the synthesis and activation of
fatty acids for the formation of phospholipids for
incorporation into the myelin membrane;(ii) to determine the sub-cellular location of these enzymes;(iii) to investigate the effect of thyroid hormone on the activity of these enzymes and (iv) to determine the route of fatty acid incorporation into myelin lipids. The results presented indicate (i) that the activities of fatty acid
synthetase and palmitoyl-CoA synthetase increase during the period of myelination; (ii) fatty acid synthetase is found predoninantly in the cytoplasmic fraction from brain homogenates, whereas palmitoyi-CoA synthetase activity is present in all menribrane fractions, although activity measured in myelin may be due to contamination; (iii) the administration of thyroid hormone has no effect on palmitoyl-CoA, synthetase, whereas
its specific antagonist, propylthiouracil, causes
a decrease in enzyme activity in the mitochondria enriched fraction; (iv) the accumulation of radioactivity
in the myelin fraction from labelled fatty.: acid
involves all subcellular organelles
including the cytoplasm and no precursor-product relationship is apparent. The results will be considered in the light of data available for lipo- genic and other enzymes involved in lipid synthesis.