Alpha-Hydroxylation of lignoceric and nervonic acids in the brain. Effects of altered thyroid function on postnatal development of the hydroxylase activity.

S Murad,G D Strycharz,Y Kishimoto

doi:10.1016/s0021-9258(17)33152-6

Abstract

Rat brain postnuclear preparations catalyzed the alpha-hydroxylation of nervonic acid with an apparent Km of 3 muM. Evidence has been presented which suggests that nervonic acid in the brain is hydroxylated by the same enzyme system which hydroxylates lignoceric acid. The hydroxylase activity in brains of normal (euthyroid) rats increased rapidly from a low in the period immediately following birth to a maximum at the 23rd day and then declined to a low level characteristic of the mature brain. Neonatal hypothyroidism retarded the development of the activity and shifted its peak to the 39th day after birth. Conversely, neonatal hyperthyroidism accelerated the entire developmental pattern and shifted the peak to the 16th day after birth. The hydroxylase activity in mouse brain was also increased by thyroid hormone administration from the 13th through the 18th day after birth. Unlike normal mice, the low activity in jimpy mice was not affected by this treatment. It is concluded that thyroid hormones play an important role in the control of brain fatty acid alpha-hydroxylation. The stimulation of alpha-hydroxy fatty acid synthesis in response to hyperthyroidism during the early postnatal period may be one of the major effects of thyroid hormones in accelerating myelination of the central nervous system.

Highlights

IntroductionTions in this laboratory [3,4,5]
It has been demonstrated both in The factors which regulate cu-hydroxy fatty acid synthesis uiuo [6, 7] and in vitro [3] that cerebronic acid in the brain is are not known but the endocrine system, thyroid synthesized from lignoceric acid
The LY- impairs the deposition of cerebroside and sulfatide (10, ll), hydroxylation reaction appears to be tightly linked to cerebro- and decreases the proportion of C, fatty acids [12]

Summary

Introduction

Tions in this laboratory [3,4,5] It has been demonstrated both in The factors which regulate cu-hydroxy fatty acid synthesis uiuo [6, 7] and in vitro [3] that cerebronic acid in the brain is are not known but the endocrine system, thyroid synthesized from lignoceric acid. This hydroxylation occurs by hormones, exerts a marked influence on myelination. The biosynthesis of cu-hydrox- sulfatide syntheses are reduced by hypothyroidism [10, 12]

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Conclusion