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41.
F. Rubio F. de Grazia B.J. Miwa W.A. Garland 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1982,233(1):149-155
A method is described for measuring (-)-threo-chlorocitric acid in human plasma. Plasma is acidified to pH 1 to minimize lactonization and a13C analogue of (-)-threo-chlorocitric acid is added as internal standard. The acidified plasma is then extracted with ethyl acetate containing 10% methanol. The ethyl acetate—methanol extract is back-extracted with acetate buffer (pH 5). This extract, following adjustment to pH 1, is reextracted with ethyl acetate. The residue after removal of the ethyl acetate is treated with ethereal diazomethane. The wet residue is reconstituted in ethyl acetate and a portion of this solution is analyzed by gas chromatography—chemical ionization mass spectrometry. The mass spectrometer is set to monitorm/z269 [MH+ of trimethylated (-)-threo-chlorocitric acid] andm/z270 [MH+ of trimethylated (-)-threo-[13C]chlorocitric acid] in the gas chromatographic effluent. Them/z/269 tom/z270 ion ratio in a sample containing an unknown amount of (-)-threo-chlorocitric acid is converted to an amount of compound using a calibration curve. The calibration curve is generated by analyzing control plasma spiked with various known amounts of (-)-threo-chlorocitric acid and a fixed amount of (-)-threo-[13C]chlorocitric acid. The limit of quantitation is 0.1–0.6 μg ml−1, depending on the characteristics of the calibration curve generated with each set of samples. The precision (relative standard deviation) at a concentration of 2 μg ml−1 is 3.3%. 相似文献
42.
A thiosulfate-oxidizing enzyme was partially purified fromChromatium vinosum, and some of its properties were studied. The enzyme rapidly reducede HiPIP (high-potential nonheme iron protein) in the
presence of thiosulfate. Cytochromesc of yeast and tuna and ferricyanide also acted well as electron acceptors for the enzyme; horse cytochromec was a poor electron acceptor. Cytochromec-552, cytochromec′, and cytochromec-553 did not act as electron acceptors. The enzyme was inhibited by cyanide and sulfite. On the basis of the stoichiometry
in reduction of ferricyanide catalyzed by the enzyme in the presence of thiosulfate, the oxidized product of thiosulfate was
inferred to be tetrathionate. 相似文献
43.
On aerobic incubation of rat cerebral cortex slices with anomers ofd-glucose and with 2-deoxy-d-glucose (2DG) for 5 min, the disappearance of -d-glucose from the incubation mixture was greater than that of -d-glucose and both anomers had a greater rate of disappearance than that of 2DG. In addition, there were significantly greater consumption of oxygen and production of lactate with the -anomer than with the -anomer. In similar experiments with3H-labeledd-glucose anomers and [1-3H]-3-O-methyl-d-glucose (3MG), the accumulation of [1-3H]--d-glucose (up to 5 min) by rat cerebral cortex slices was greater than that of [1-3H]--d-glucose. Although initially lower than that of the anomers, the accumulation of [1-3H]-3MG increased at a greater rate and, by 5 min of incubation, was greater than that of both glucose anomers. This preferential accumulation was seen to disappear when the slices were preincubated with 2DG (hexokinase inhibitor) or when the temperature of incubation was reduced to 20°C. Under those conditions the data with the glucose anomers were similar to those obtained with 3MG. Our data then suggested that the greater accumulation of -d-glucose than of -d-glucose by the slices was probably not due to differences in transport through brain cell membranes but rather to the preferential metabolism of the -d-glucose. 相似文献
44.
Characterization of Temperature-Sensitive, Fertilization-Defective Mutants of the Nematode CAENORHABDITIS ELEGANS 总被引:12,自引:3,他引:9
The isolation and characterization of three Caenorhabditis elegans temperature-sensitive mutants that are defective at fertilization are described. All three are alleles of the gene fer-1. At the restrictive temperature of 25 degrees, mutant hermaphrodites make sperm and oocytes in normal numbers. No oocytes are fertilized, although they pass through the spermatheca and uterus normally. The oocytes can be fertilized by sperm transferred by wild-type males, indicating that the mutant defect is in the sperm. The temperature-sensitive period for the mutants coincides with spermatogenesis. Sperm made by mutants at 25 degrees cannot be distinguished from wild-type sperm by light microscopy. The sperm do contact oocytes in mutant hermaphrodites, but do not fertilize. Mutant sperm appear to be nonmotile. Mutant males are also steril when grown at 25 degrees. They trnasfer normal numbers of sperm to hermaphrodites at mating, but these sperm fail to migrate to the spermatheca and are infertile. The phenotype of these mutants is consistent with a primary defect in sperm motility, but the cause of this defect is not known. 相似文献
45.
1. Glutathione reductase (NAD(P)H:oxidized-glutathione oxidoreductase, EC. 1.6.4.2) from human erythrocytes was purified 49 000-fold with an overall yield of 15% and a 280/460 nm absorbance ratio of 6.03. The procedure used was the method of Worthington and Rosemeyer modified by addition of heating and recrystallization. 2. It was concluded from the results of purification, electrofocusing and inhibition studies that glutathione reductase is a single enzyme which used both NADPH and NADH as hydrogen donors. 3. Apoenzyme cross-reacts with the antibody to the holoenzyme but has a slightly reduced affinity to the antibody. Apoenzyme can be removed from the hemolysate by heating and centrifugation without loss of holoenzyme. 4. Indirect immunological assay of the specific activity of the erythrocyte glutathione reductase is possible in the enzyme saturated with FAD. 相似文献
46.
47.
The Role of Influenza A Virus Hemagglutinin Residues 226 and 228 in Receptor Specificity and Host Range Restriction 总被引:18,自引:8,他引:18 下载免费PDF全文
Angela Vines Krisna Wells Mikhail Matrosovich Maria R. Castrucci Toshihiro Ito Yoshihiro Kawaoka 《Journal of virology》1998,72(9):7626-7631
Influenza A viruses can be isolated from a variety of animals, but their range of hosts is restricted. For example, human influenza viruses do not replicate in duck intestine, the major replication site of avian viruses in ducks. Although amino acids at positions 226 and 228 of hemagglutinin (HA) of the H3 subtype are known to be important for this host range restriction, the contributions of specific amino acids at these positions to restriction were not known. Here, we address this issue by generating HAs with site-specific mutations of a human virus that contain different amino acid residues at these positions. We also let ducks select replication-competent viruses from a replication-incompetent virus containing a human virus HA by inoculating animals with 1010.5 50% egg infectious dose of the latter virus and identified a mutation in the HA. Our results showed that the Ser-to-Gly mutation at position 228, in addition to the Leu-to-Gln mutation at position 226 of the HA of the H3 subtype, is critical for human virus HA to support virus replication in duck intestine. 相似文献
48.
Sakuo Hoshi Takashi Odawara Masamichi Oshima Yoshihiro Kitamura Hajime Takizawa Hiroshi Yoshikura 《Biochemical and biophysical research communications》2002,290(3):1139-1144
Murine leukemia virus (MLV) produces the unspliced RNA and the singly spliced RNA at a proper ratio at a time. To identify cis-elements involved in the production of the unspliced RNA, we examined the level of unspliced RNA in a series of mutants derived from a prototype Moloney MLV mutant gag-encoding G3.6. Our present data indicated that nt 1560-1906 region in the CA-encoding region in gag was the negative cis-element and nt 5119-5355 region, which was immediately upstream of the splice acceptor site, was the positive cis-element for expression of the unspliced RNA. It was found that the former element made expression of the unspliced RNA dependent upon the latter. These two elements were functional as discrete elements and their activities were relatively position-independent. 相似文献
49.
Yoshihiro Uesawa 《Bioorganic & medicinal chemistry letters》2018,28(20):3400-3403
Quantitative structure–activity relationship (QSAR) analysis uses structural, quantum chemical, and physicochemical features calculated from molecular geometry as explanatory variables predicting physiological activity. Recently, deep learning based on advanced artificial neural networks has demonstrated excellent performance in the discipline of QSAR research. While it has properties of feature representation learning that directly calculate feature values from molecular structure, the use of this potential function is limited in QSAR modeling. The present study applied this function of feature representation learning to QSAR analysis by incorporating 360° images of molecular conformations into deep learning. Accordingly, I successfully constructed a highly versatile identification model for chemical compounds that induce mitochondrial membrane potential disruption with the external validation area under the receiver operating characteristic curve of ≥0.9. 相似文献
50.
The design and synthesis of a new tumor-selective fluoropyrimidine carbamate, capecitabine 总被引:13,自引:0,他引:13
Shimma N Umeda I Arasaki M Murasaki C Masubuchi K Kohchi Y Miwa M Ura M Sawada N Tahara H Kuruma I Horii I Ishitsuka H 《Bioorganic & medicinal chemistry》2000,8(7):1697-1706
To identify an orally available fluoropyrimidine having efficacy and safety profiles greatly improved over those of parenteral 5-fluorouracil (5-FU: 1), we designed a 5-FU prodrug that would pass intact through the intestinal mucisa and be sequentially converted to 5-FU by enzymes that are highly expressed in the human liver and then in tumors. Among various N4-substituted 5'-deoxy-5-fluorocytidine derivatives, a series of N4-alkoxycarbonyl derivatives were hydrolyzed to 5'-deoxy-5-fluorocytidine (5'-DFCR: 8) specifically by carboxylesterase, which exists preferentially in the liver in humans and monkeys. Particularly, derivatives having an N4-alkoxylcarbonyl moiety with a C4-C6 alkyl chain were the most susceptible to the human carboxylesterase. Those were then converted to 5'-deoxy-5-fluorouridine (5'-DFUR: 4) by cytidine deaminase highly expressed in the liver and solid tumors and finally to 5-FU by thymidine phosphorylase (dThdPase) preferentially located in tumors. When administered orally to monkeys, a derivative having the N4-alkoxylcarbonyl moiety with a C5 alkyl chain (capecitabine: 6) The highest AUC and Cmax for plasma 5'-DFUR. In tests with various human cancer xenograft models, capecitabine was more efficacious at wider dose ranges than either 5-FU or 5'-DFUR and was significantly less toxic to the intestinal tract than the others in monkeys. 相似文献