• Journal of the Korean Applied Science and Technology
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• v.29 no.1
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• pp.71-80
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• 2012

Vinca alkaloids produced from Catharanthus roseus are one of the most important natural product drugs in treatments of human cancers. These anticancer drugs are derived from coupling of the two monomeric indole alkaloids, catharanthine and vindoline. In order to investigate vindoline biosynthesis, tabersonine-$CD_3$ 1a is synthesized to use as a deuterium labeled precursor, which is distinguished clearly from the natural counterpart. We show that these deuterium labeled tabersonine 1a are successfully incorporated into the vindoline biosynthetic pathway to yield three deuterated vindoline intermediates. 16-Hydroxytabersonine-$CD_3$ (m/z 356) 2a, 16-Methoxytabersonine-$CD_3$ (m/z 370) 3a, 16-Methoxy-2,3-dihydro-3-hydroxytabersonine-$CD_3$ (m/z 388) 4a are produced from the cell suspension culture measured by UPLC/MS at 5 and 13 days after feeding tabersonine. The conversion rates from 1a to 2a and 2a to 3a are fast, whereas that from 3a to 4a is much slower. This indicates that the rate determining step among the first three vindoline biosynthesis is the last step. As a result of the slow conversion rate from 3a to 4a, the accumulation level of 16-Methoxytabersonine-$CD_3$ 3a is significantly increased up to 13 days. The accumulation ratio among 2a, 3a and 4a is 1, 2 and 0.1 at 5 days. However, the peaks of desacetoxyvindoline-$CD_3$ 5a, deacetylvindoline-$CD_3$ 6a and vindoline-$CD_3$ 7a are not found from the cell extracts even after 13 days of incubation which may indicate no presence of their corresponding enzymes.

• Applied Biological Chemistry
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• v.7
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• pp.21-27
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• 1966

This experiment was performed to investigate the effect of the frequency of meals on the metatolism and the body composition of rats when equal amount of purified diet was ingested. Thirty approximately days old rats weighing 290 g and thirty-two about 40 days old rats weighing 180 g were employed for the period of 34 days. Rats fed ad libitum (10 to 15 meals per day) and two-meal per day were pair-fed and equal amount of diet was fed to each rat in pair. The experimental results obtained are summarized as follows: 1. Frequency of meal did not exert any effect on the body weight gain. However, rats fed two-meal per· day gained significantly (p <0.005) more fat and energy than ad libitum group. The rate of gain of protein in ad libitum group was higher than that of two-meal group. No difference was observed for the mineral deposition of rat body. 2. From the preperation of rat liver it was found that the activity of glucose-6-phosphate dehydrogenase was much higher for the rats fed two-meals per day than those fed ad libitum. Therefore, it is suggested that the metabolic pathway of carbohydrate for two-meal group has been shifted from glycolysis to Hexose Monophosphate Shunt and produced more NADPH which would be the essential cofactor of fatty acids synthesis. 3. The rate of excretion of urinary nitrogen for two-meal group was significantly (p<0.005) higher than that of ad libitum group. It is apparent that considerable amount of over-loaded amino acids by feeding two-big-meal daily· could not be used for the protein biosynthesis all at once and excreted following deamination through urine. The residual carbon chain could be served as a precursor of fatty acids synthesis. 4. The heat production rate of rats fed two-meal group was significantly (p<0.005) lower than that of ad libitum group. It seems possible that the activity of thyroid gland (and consequently BMR) can be depressed by the frequency of meal.

• Tuberculosis and Respiratory Diseases
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• v.45 no.4
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• pp.723-735
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• 1998

Background : Vitamin C has been reported to have a role in the decrease of airway hyperresponsiveness in animal models. This data is based on some metabolic actions of vitamin C, such as promotion of histamine degradation, producing more $PGE_2$ than $PGF_{2\alpha}$ in cyclooxygenase pathway, decrease of smooth muscle contraction, and acting as reducing agent of oxidant. It has been also known that heavy smokers have lower blood levels of vitamin C than nonsmokers and this deficiency in heavy smokers have been explained by several mechanisms, such as increased oxidation by oxidants and free radicals, increased biosynthesis of catecholamine and serotonin released by nicotine, and inadequate dietary intake. In this study, We attempted to assess effect of vitamin C on bronchial hyperresponsiveness in heavy smokers who have bronchial hyperresponsiveness and role of vitamin C on bronchial hyperresponsiveness. Method: To assess acute effect of vitamin C on airway hyperresponsiveness, blood sample for vitamin C level and spirometry, methacholine challenge test were done in 17 smokers and 8 nonsmokers, and one hour after oral administration of vitamin C 3 g, blood sample for vitamin C level and spirometry, methacholine challenge test were repeated. To assess chronic effect of vitamin C on airway hyperresponsiveness, after daily administration of vitamin C 1 g for one week in 17 smokers, blood sample for vitamin C level and spirometry, methacholine challenge test were done. To assess role of vitamin C, after oral administration of vitamin C 3 g plus indomethacin 100 mg in 12 of 15 smokers who were reactive to methacholine challenge test, spirometry and methacholine challenge test were done and after oral intake of indomethacin 100 mg in 12 smokers who were reactive to methacholine challenge test, spirometry and methacholine challenge test were repeated. Result: There were no significant differences in whole blood vitamin C levels between smokers($1.17{\pm}0.22$ mg/dL) and nonsmcikers($1.14{\pm}0.19$ mg/dL) (p>0.05). Fifteen of the 17 smokers(88.2%) were reactive to methacholine challenge test and 10 of the 15 smokers who were reactive to methacholine challenge test were less than 8 mg/dL in $PC_{20}FEV-2$, and 7 of the 8 nonsmokers(87.5%) were nonreactive to methacholine challenge test There were significant decrease in bronchial responsiveness after oral administration of vitamin C 3 g in 13 of the 15 smokers who were reactive to methacholine challenge test This significant decrease persisted with maintenance daily administration of 1 g for one week. $PC_{20}FEV-2$ were not correlated to vitamin C levels in smokers. After oral administration of indomethacin 100 mg, significant reduction of bronchial responsiveness that occured after oral administration of vitamin C 3 g in smokers were attenuated. Conclusion: Although there were no significant differences in whole blood vitamin C levels between smokers and nonsmokers. heavy smokers have significant increase in bronchial responsiveness than nonsmokers. This bronchial hyperresponsiveness of heavy smokers can be attenuated by vitamin C supplement. Disappearance of vitamin C effect by indomethacin supplement may suggest that vitamin C exert its effect via alteration of arachidonic acid metabolism.