Enzymes of Fatty Acid β‐Oxidation in Developing Brain

Abstract

Developmental profiles were determined for the activities of eight enzymes involved in fatty acid β-oxida-tion in rat brain. The enzymes studied were the palmitoyl-CoA, octanoyl-CoA, butyryl-CoA, glutaryl-CoA, and 3-hy-droxyacyl-CoA dehydrogenases, the enoyl-CoA hydratase (crotonase), and the C₄- and C₁₀-thiolases. With the exception of the thiolases, all of the activities (expressed on the basis of brain weight) increased during the postnatal period of brain maturation. The activity of octanoyl-CoA dehy-drogenase was elevated markedly compared to that of pal-mitoyl-CoA dehydrogenase at all developmental stages and in all brain regions in the rat. A similar relationship between these enzymes was observed in various regions of adult human brain. Comparisons of the activities of the β-oxidation enzymes in human brain versus human skeletal muscle and in cultured neural cell lines (neuroblastoma and glioma) versus cultured skin fibroblasts revealed that the elevated activity of octanoyl-CoA dehydrogenase relative to palmitoyl-CoA dehydrogenase was specific to the neural tissues. This relationship was particularly evident when the enzyme activities were normalized to the activity of crotonase. The data support previous findings with ra-diochemical tracers, indicating that the brain is capable of utilizing fatty acids as substrates for oxidative energy metabolism. The relatively high activity of the medium-chain fatty acyl-CoA dehydrogenase in neural tissue may represent an adaptive mechanism to protect the brain from the known encephalopathic effects of octanoate and other medium-chain fatty acids that readily cross the blood-brain barrier.