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91.
Kitagawa T 《Proceedings of the Japan Academy. Series B, Physical and biological sciences》2012,88(5):192-200
In 1957 Sakai and Kitagawa in Japan reported the clinical and biochemical findings in a patient with tyrosinemia, tyrosyluria, liver cirrhosis, and renal rickets. Subsequently, reports were published from various countries of other patients with hepatorenal tyrosinemia (HRT). 4-Hydroxyphenylpyruvate dioxygenase deficiency was originally proposed as the cause of HRT. However, in 1977 Lindblad et al. found that succinylacetone, which accumulates in the serum and urine from patients with HRT, inhibits delta-aminolevulinic acid (ALA) dehydratase in vitro. They suggested that the primary enzyme deficiency in patients with HRT was fumarylacetoacetate hydrolase, and this was soon confirmed. Thus, the elucidation of the pathogenesis of this disease has led to the possibility that, if a reliable newborn screening method could be developed, the prognosis of these patients would be improved. Early treatment would require a diet low in phenylalanine and tyrosine, administration of 2-(2-nitoro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC), and liver transplantation. 相似文献
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94.
Thierry Fouquet Hiroaki Sato Yusuke Nakamichi Akinori Matsushika Hiroyuki Inoue 《Journal of mass spectrometry : JMS》2019,54(3):213-221
A rapid analytical methodology is proposed to answer the two questions about the molecular and structural features of the acidic xylo‐oligosaccharides (XOSs) formed upon the enzymatic hydrolysis of 4‐O‐methylglucuronoxylan. The shortest acidic XOSs carrying a methylglucuronic acid moiety and the possible distribution of larger products (molecular feature) are instantly found by electrospray ionization mass spectrometry (ESI‐MS) in the negative ion mode, which filters the unwanted neutral XOS. The acidic moiety is then unambiguously localized along the xylose backbone (structural feature) by ESI‐MSn in the negative ion mode via the selection/activation/dissociation of the product ions formed upon the one‐way and stepwise glycosidic bond cleavage at the reducing end. Using the shortest acidic XOS with a known shape generated by glycoside hydrolase family (GH) 10 and GH11 xylanases as a proof of principle, pairs of diagnostic ions are proposed to instantly interpret the MSn fingerprints and localize the acidic moiety along the xylose chain of the activated ion. The original structure of the acidic XOS is then reconstructed by adding as many xylose units at the reducing end as MSn steps. Relying on pairs of ions, the methodology is robust enough to highlight the presence of isomeric products. Mass spectra reported in the present article will be conveniently used as reference data for the forthcoming analysis of acidic XOS generated by new classes of enzymes using this multistage mass spectrometry methodology. 相似文献
95.
Kohei Azami Taiki Hayashi Takenori Kusumi Ken Ohmori Keisuke Suzuki 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2019,131(16):5375-5380
The first total synthesis of carthamin ( 3 ), a historic natural red pigment, has been achieved. The molecular structure was efficiently constructed by assembling two equivalents of the in situ generated lithiated monomers and triisopropyl orthoformate. This synthesis confirms the structure proposed in 1996. 相似文献
96.
Yubao Shan Xiaoling He Zi Wang Xiali Yue Jiang Zhu Yunhuang Yang Maili Liu 《Molecules (Basel, Switzerland)》2021,26(18)
Clostridium perfringens autolysin (CpAcp) is a peptidoglycan hydrolase associated with cell separation, division, and growth. It consists of a signal peptide, ten SH3b domains, and a catalytic domain. The structure and function mechanisms of the ten SH3bs related to cell wall peptidoglycan binding remain unclear. Here, the structures of CpAcp SH3bs were studied through NMR spectroscopy and structural simulation. The NMR structure of SH3b6 was determined at first, which adopts a typical β-barrel fold and has three potential ligand-binding pockets. The largest pocket containing eight conserved residues was suggested to bind with peptide ligand in a novel model. The structures of the other nine SH3bs were subsequently predicted to have a fold similar to SH3b6. Their ligand pockets are largely similar to those of SH3b6, although with varied size and morphology, except that SH3b1/2 display a third pocket markedly different from those in other SH3bs. Thus, it was supposed that SH3b3-10 possess similar ligand-binding ability, while SH3b1/2 have a different specificity and additional binding site for ligand. As an entirety, ten SH3bs confer a capacity for alternatively binding to various peptidoglycan sites in the cell wall. This study presents an initial insight into the structure and potential function of CpAcp SH3bs. 相似文献
97.
Background: Cardiovascular diseases have consistently been the leading cause of death in the United States over the last two decades, with 30% of the adult American population having hypertension. The metabolites of arachidonic acid (AA) in the kidney play an important role in blood pressure regulation. The present study investigates the antihypertensive effect of honokiol (HON), a naturally occurring polyphenol, and examines its correlation to the modulation of AA metabolism. Methods: Spontaneously hypertensive rats (SHR) were randomly divided into four groups. Treatment groups were administered HON intraperitoneally at concentrations of 5, 20, and 50 mg/kg. Blood pressure was monitored at seven-day intervals. After a total of 3 weeks of treatment, the rats were euthanized and the kidney tissues were collected to examine the activity of the two major enzymes involved in AA metabolism in the kidney, namely cytochrome P450 (CYP)4A and soluble epoxide hydrolase (sEH). Results: Rats treated with HON did not experience the rise in blood pressure observed in the untreated SHR. High-dose HON significantly reduced blood pressure and inhibited the activity and protein expression of the CYP4A enzyme in the rat kidney. The activity of the sEH enzyme in renal cytosol was significantly inhibited by medium and high doses of HON. Conclusion: Our data demonstrate the antihypertensive effect of HON and provide a novel mechanism for its underlying cardioprotective properties. 相似文献
98.
β-榄香烯含S,Se糖苷衍生物的设计合成 总被引:1,自引:0,他引:1
以β-榄香烯(1)为先导化合物, 经由其13位氯代物(2), 依据生物电子等排原理将具有相似共价半径的杂原子S和Se分别引入到β-榄香烯的骨架中, 得到一对相应的类似物3和6; 进而通过多种方法与系列糖供体对接, 立体选择性地合成了相应的乙酰化1,2-反式糖苷类衍生物11a~11c和12a~12c, 经水解脱去保护基团, 得到目标产物β-榄香烯含S糖苷13a~13c及其类似物β-榄香烯含Se糖苷14a~14c. 目标化合物的结构经IR, 1H NMR, 13C NMR, 77Se NMR, HRMS等方法确证. 相似文献
99.
We describe our studies on the synthesis of carotenoid glucosides and deoxyglucosides using the acetimidate method and the Ferrier rearrangement, respectively. In both cases the reaction conditions were optimized until the yields were superior to those of previously published glycosylations. 相似文献
100.
《Electroanalysis》2004,16(22):1896-1906
Recent world‐wide terrorist events associated with the threat of hazardous chemical agent proliferation, and outbreaks of chemical contamination in the food supply has demonstrated an urgent need for sensors that can directly detect the presence of dangerous chemical toxins. Such sensors must enable real‐time detection and accurate identification of different classes of pesticides (e.g., carbamates and organophosphates) but must especially discriminate between widely used organophosphate (OP) pesticides and G‐ and V‐type organophosphate chemical warfare nerve agents. Present field analytic sensors are bulky with limited specificity, require specially‐trained personnel, and, in some cases, depend upon lengthy analysis time and specialized facilities. Most bioanalytical based systems are biomimetic. These sensors utilize sensitive enzyme recognition elements that are the in‐vivo target of the neurotoxic agents which the sensor is attempting to detect. The strategy is well founded; if you want to detect cholinesterase toxins use cholinesterase receptors. However, this approach has multiple limitations. Cholinesterase receptors are sensitive to a wide range of non‐related compounds and require lengthy incubation time. Cholinesterase sensors are inherently inhibition mode and therefore require baseline testing followed by sample exposure, retest and comparison to baseline. Finally, due to the irreversible nature of enzyme‐ligand interactions, inhibition‐mode sensors cannot be reused without regeneration of enzyme activity, which in many cases is inefficient and time‐consuming. In 1996, we pioneered a new “kinetic” approach for the direct detection of OP neurotoxins based on agent hydrolysis by the enzyme organophosphate hydrolase (OPH; EC 3.1.8.2; phosphotriesterase) and further identified a novel multi‐enzyme strategy for discrimination between different classes of neurotoxins. The major advantage of this sensor strategy is it allows direct and continuous measurement of OP agents using a reversible biorecognition element. We also investigated incorporation of enzymes with variations in substrate specificity (e.g., native OPH, site‐directed mutants of OPH, and OPAA (EC 3.1.8.1), based upon preferential hydrolysis of P? O, P? F and P? S bonds to enable discrimination among chemically diverse OP compounds. Organophosphate hydrolase enzymes were integrated with several different transduction platforms including conventional pH electrodes, fluoride ion‐sensitive electrodes, and pH‐responsive fluorescent dyes. Detection limit for most systems was in the low ppm concentration range. This article reviews our integration of organophosphate hydrolase enzymes with pH sensitive field effect transistors (FETs) for OP detection. 相似文献