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JBC, Vol. 250, Issue 15, 5841-5846, Aug, 1975

Alpha hydroxylation of lignoceric acid to cerebronic acid during brain development. Diminished hydroxylase activity in myelin-deficient mouse mutants

S. Murad and Y. Kishimoto

Alpha Hydroxylation of lignoceric acid (n-tetracosanoic acid) to cerebronic acid (2-hydroxylignoceric acid) by postnuclear preparations of brains from developing rat, mouse, and several neurological mouse mutants was studied. The preparations of brains from jimpy and myelin synthesis deficiency (msd) mice were found to synthesize cerebronic acid at less than 10 percent of their control rates, and those from quaking and dilute-lethal approximately 30 and 50 percent, respectively. The apparent low rate of in vitro hydroxylation by brains of the mutant mice appeared to be due to decreased synthesis rather than increased oxidation of cerebronic acid. Mixing experiments eliminated the possibility of an inhibitor in the mutant or an activator in normal animals. The preparations of brains from wabbler-lethal, ducky, and weaver mice showed normal activity. The developmental pattern of the hydroxylase activity was examined in quaking, jimpy, and their control mice. In normal brains the hydroxylase activity was low in the immediate postnatal period, increased sharply between 10 and 20 days after birth, and fell to a low level following maturation of the brain. The hydroxylase activity in quaking mice changed similarly during brain development but at a much reduced level. The brains of jimpy mice had barely detectable hydroxylase activity which changed little with age and reached a peak at about 15 days postpartum. The subnormal hydroxylase activity in brains of quaking mice and the near absence in brains of jimpy and msd mice correlate with the observations that myelin deficiency is more severe in jimpy and msd than in quaking. These results suggest a close association of the synthesis of cerebronic acid with the synthesis of the characteristic myelin lipid that is cerebroside (N-acyl sphingosine beta-D-galactoside).
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