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The importance of myristoylation for the proper biological functioning of many acylated proteins has generated interest in the enzymes of the myristoylation pathway and their interactions with substrates and inhibitors. Previous observations that S-(2-oxopentadecyl)-CoA, a nonhydrolyzable methylene-bridged analogue of myristoyl-CoA, was a potent inhibitor of myristoyl-CoA:protein N-myristoyltransferase (NMT) [Paige, L. A., Zheng, G.-q., DeFrees, S. A., Cassady, J. M., & Geahlen, R. L. (1989) J. Med. Chem. 32, 1665] prompted a closer examination of the effect of substituents at the 2-position on the interactions of myristic acid and myristoyl-CoA analogues with NMT. As an initial approach, three myristic acid derivatives bearing different substituents at the 2-position, 2-fluoromyristic acid, 2-bromomyristic acid, and 2-hydroxymyristic acid, were selected for study. Both 2-bromomyristic acid and 2-hydroxymyristic acid were available commercially; 2-fluoromyristic acid was prepared synthetically. All three compounds were found to be only weak inhibitors of NMT in vitro. Of the three, 2-bromomyristic acid was the most potent (Ki = 100 microM). In cultured cells, however, 2-hydroxymyristic acid was by far the more effective inhibitor of protein myristoylation. Neither 2-hydroxymyristic acid nor 2-bromomyristic acid significantly inhibited protein palmitoylation in cultured cells, indicating that inhibition was not occurring at the level of acyl-CoA synthetase. Activation of the 2-substituted myristic acid derivatives to their corresponding acyl-CoA thioesters by acyl-CoA synthetase resulted in inhibitors of greatly increased potency. The 2-substituted acyl-CoA analogues, 2-hydroxymyristoyl-CoA, 2-bromomyristoyl-CoA, and 2-fluoromyristoyl-CoA, were synthesized and shown to be competitive inhibitors of NMT in vitro (Ki's = 45, 450, and 200 nM, respectively). These data suggested that the enhanced inhibitory potency of 2-hydroxymyristic acid seen in cells was most probably a result of its metabolic activation to the CoA thioester. The presence of substituents at the 2-position also affected the ability of the acyl group to be transferred by NMT to a peptide substrate. Of the three acyl-CoA analogues, only 2-fluoromyristoyl-CoA served as a substrate for NMT.

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High-temperature weather appears in high frequency, big strength, and long duration in the summer. It is therefore important to study the effects of high-temperature weather on sleep quality and appetite. Ten healthy college students were selected as subjects. The experiment conditions were divided by the daily maximum temperature into 28 °C, 32 °C, 36 °C, and 38 °C. The objective sleep quality was measured by an intelligent sleep monitoring belt, and the subjective sleep quality was measured by a questionnaire survey. The subjective appetites were assessed by a visual analog scale (VAS), and the objective appetites were assessed by the meal weight and the meal time. For sleep quality, the objective results indicated that the sleep quality at 32 °C was the best, followed by 28 °C, while the sleep quality at 36 °C and 38 °C was the worst. Significant effects were mainly reflected in sleep duration and shallow sleep. The subjective results showed that temperature had significant effects on sleep calmness, difficulty in falling asleep, sleep satisfaction, and sleep adequateness. For appetite, the VAS results indicated that high temperatures mainly led to a reduction of appetite at lunch time. The meal weights of lunch were larger than those of supper except for 28 °C, and the meal time of lunch and supper was longer than that of breakfast. The meal time of lunch was longer than that of supper except for 36 °C. This paper can provide a study method and reference data for the sleep quality and appetite of human in high-temperature weather.

Guided by the glutathione S-transferase (GST) assay, fractionation of lemongrass oil and galanga root oil from the plants Cymbopogon citratus and Alpinia galanga , respectively, led to the isolation of four active compounds: d-limonene (1) and geraniol (2) from lemongrass oil; ethyl trons-cinnamate (3) and ethyl 4-methoxy-trons-cinnamate (4) from galanga root oil. Their structures were determined on the basis of spectral analysis. These compounds were tested for their capacity to induce the activity of the detoxifying enzyme, GST, in several tissues of female A/J mice. Compound 1 increased GST activity 2.4-3.0-fold higher than controls in the mouse liver and mucosa of the small intestine and large intestine. Compound 2 showed high GST-inducing activity only in the mucosa of the small intestine and large intestine (about 2.5-fold greater than controls). Compounds 3 and 4 exhibited significant activity in the mouse liver and intestines. Induction of increased GST activity, which is believed to be a major mechanism for chemical carcinogen detoxification, has been recognized as one of the characteristics of the action of anticarcinogens. Thus, these compounds show promise as potential chemopreventive agents.(Poaceae or Gramineae) (Formacek and Kubcezka, 1982).C. citratus, native of Sri Lanka and India, now grows only under cultivation in India, Africa, the Philippines, Madagascar, Central and South America, the West Indies, and southeast Asia. Lemongrass oil is used mainly in food flavorings and to a lesser extent in perfumery. Galanga

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