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S Murad

Publications and source records attributed to S Murad.

65 records · Page 4Linked to original sources
PubMed1977

alpha-Hydroxylation of fatty acids in brain. Substrate specificity and deuterium isotope effect.

The alpha-hydroxylation of fatty acids with various chain length by a rat brain postnuclear preparation was investigated. The maximum velocity of the alpha-hydroxylation were higher for lignoceric (tetracosanoic), tricosanoic, docosanoic, and heneicosanoic acids and lower for hexacosanoic, pentacosanoic, eicosanoic, and nonadecanoic acids. Stearic palmitic, and phytanic (3,7,11,15-tetramethylpalmitic) acids were not hydroxylated by this preparation. Apparent Km values were lower for fatty acids with the higher Vmax and higher for those with the lower Vmax values. The relative order of alpha-hydroxylation strongly resembles the relative distribution of these fatty acids in brain cerebrosides, and we suggest that alpha-hydroxylation plays an important role in determining this distribution. An improved synthesis of [U-14C]phytanic acid is described. The rate of alpha-hydroxylation with [2-2H2]lignoceric acid was one-fifth of nondeuterated lignoceric acid and one-third of [3-2H2]lignoceric acid, while apparent Km values for these acids were similar. The reduced rate with [2-2H2]lignoceric acid indicates that the cleavage of the C-H bond is the rate-limiting step of the alpha-hydroxylation.

Animals↗
PubMed1976

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

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.

Aging↗
PubMed1975

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

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).

Aging↗