Chain elongation of fatty acid in brain: A comparison of mitochondrial and microsomal enzyme activities

Abstract

The activities of mitochondrial and microsomal fatty acid-elongating enzymes have been measured in rat brain during postnatal development and in brains of jimpy, msd, and quaking mice. The microsomal enzyme activity rose from a low in the immature brain to a maximum at 21 days of age and then declined to low levels in the mature brain. The developmental patterns were similar for all acyl-CoAs tested. The maximum activity fell sharply from C 16 to C 18 and then fell gradually with increase in fatty acid chain length up to C 24. The activities for monounsaturated acyl-CoAs were slightly higher than for corresponding saturated esters. The mitochondrial enzyme activity was high in the immature brain and remained virtually unchanged during further brain development. This activity steadily decreased with increasing chain length from C 16 to C 24. The microsomal enzyme activity was reduced in myelin-deficient mutants compared to their controls. The extent of reduction was most severe for C 20- to C 24-CoAs followed by C 18-CoA and then C 16-CoA, for which the activity was reduced only in the jimpy mouse. The activities for C 20- to C 24-CoAs in jimpy, msd, and quaking mice were 12, 38, and 52% of the control, respectively. The mitochondrial enzyme activity was not affected by these mutations. Fatty acid synthetase activity was similar in the mutant and control mice. These results suggest that the deficiency of long-chain fatty acids in the central nervous system of myelin-deficient mouse mutants is due to reduced synthesis by the microsomal enzyme, which is directly related to myelination. The brain mitochondrial enzyme appears to be unrelated to myelination.