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91.
Glycosaparaginase from human leukocytes. Inactivation and covalent modification with diazo-oxonorvaline 总被引:1,自引:0,他引:1
V Kaartinen J C Williams J Tomich J R Yates L E Hood I Mononen 《The Journal of biological chemistry》1991,266(9):5860-5869
The apparent active site of human leukocyte glycoasparaginase (N4-(beta-acetylglucosaminyl)-L-asparaginase EC 3.5.1.26) has been studied by labeling with an asparagine analogue, 5-diazo-4-oxo-L-norvaline. Glycoasparaginase was purified 4,600-fold from human leukocytes with an overall recovery of 12%. The purified enzyme has a Km of 110 microM, a Vmax of 34 mumol x l-1 x min-1, and a specific activity of 2.2 units/mg protein with N4-(beta-N-acetylglucosaminyl)-L-asparagine as substrate. The carbohydrate content of the enzyme is 15%, and it exhibits a broad pH maximum between 7 and 9. The 88-kDa native enzyme is composed of 19-kDa light (L) chains and 25-kDa heavy (H) chains and it has a heterotetrameric structure of L2H2-type. The glycoasparaginase activity decreases rapidly and irreversibly in the presence of 5-diazo-4-oxo-L-norvaline. At any one concentration of the compound, the inactivation of the enzyme is pseudo-first-order with time. The inhibitory constant, K1, is 80 microM and the second-order rate constant 1.25 x 10(3) M-1 min-1 at pH 7.5. The enzyme activity is competitively protected against this inactivation by its natural substrate, aspartylglucosamine, indicating that this inhibitor binds to the active site or very close to it. The covalent incorporation of [5-14C]diazo-4-oxo-L-norvaline paralleled the loss of the enzymatic activity and one inhibitor binding site was localized to each L-subunit of the heterotetrameric enzyme. Four peptides with the radioactive label were generated, purified by high performance liquid chromatography, and sequenced by Edman degradation. The sequences were overlapping and all contained the amino-terminal tripeptide of the L-chain. By mass spectrometry, the reacting group of 5-diazo-4-oxo-L-norvaline was characterized as 4-oxo-L-norvaline that was bound through an alpha-ketone ether linkage to the hydroxyl group of the amino-terminal amino acid threonine. 相似文献
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94.
Objectives
Fish consumption has been associated with reduced risk of cardiovascular diseases (CVD), especially sudden cardiac death (SCD). Fish is the major source of long-chain n-3 polyunsaturated fatty acids (PUFA) eicosapentaenoic acid and docosahexaenoic acid. It is also a major source of methylmercury, which was associated with increased risk of CVD in this study population. Impact of interaction between long-chain n-3 PUFA and methylmercury on the SCD risk is unknown.Methods
A total of 1857 men from the prospective, population-based Kuopio Ischaemic Heart Disease Risk Factor study, aged 42–60 years and free of CVD at baseline in 1984–1989, were studied. Serum long-chain n-3 PUFA was used as the marker for long-chain n-3 PUFA intake and hair mercury as the marker for mercury exposure.Results
During the mean follow-up of 20.1 years, 91 SCD events occurred. In the multivariate Cox proportional hazards regression models, serum long-chain n-3 PUFA concentration was not associated with the risk of SCD until hair mercury was accounted for; then the hazard ratio (HR) in the highest vs. lowest tertile was 0.54 [95% confidence interval (CI) 0.32 to 0.91, p for trend = 0.046]. When the analyses were stratified by hair mercury content, among those with lower hair mercury, each 0.5 percentage unit increase in the serum long-chain n-3 PUFA was associated with HR of 0.77 (95% CI 0.64 to 0.93), whereas no association was seen among those with higher hair mercury (p for interaction = 0.01). Among the individual long-chain n-3 PUFA, docosahexaenoic acid was most strongly associated with the risk.Conclusion
High exposure to mercury may reduce the benefits of long-chain n-3 PUFA on SCD. 相似文献95.
96.
Background
For the cultivation of Escherichia coli in bioreactors trace element solutions are generally designed for optimal growth under aerobic conditions. They do normally not contain selenium and nickel. Molybdenum is only contained in few of them. These elements are part of the formate hydrogen lyase (FHL) complex which is induced under anaerobic conditions. As it is generally known that oxygen limitation appears in shake flask cultures and locally in large-scale bioreactors, function of the FHL complex may influence the process behaviour. Formate has been described to accumulate in large-scale cultures and may have toxic effects on E. coli. 相似文献97.
Estrogenic regulation of skeletal muscle proteome: a study of premenopausal women and postmenopausal MZ cotwins discordant for hormonal therapy 下载免费PDF全文
Eija K. Laakkonen Rabah Soliymani Sira Karvinen Jaakko Kaprio Urho M. Kujala Marc Baumann Sarianna Sipilä Vuokko Kovanen Maciej Lalowski 《Aging cell》2017,16(6):1276-1287
Female middle age is characterized by a decline in skeletal muscle mass and performance, predisposing women to sarcopenia, functional limitations, and metabolic dysfunction as they age. Menopausal loss of ovarian function leading to low circulating level of 17β‐estradiol has been suggested as a contributing factor to aging‐related muscle deterioration. However, the underlying molecular mechanisms remain largely unknown and thus far androgens have been considered as a major anabolic hormone for skeletal muscle. We utilized muscle samples from 24 pre‐ and postmenopausal women to establish proteome‐wide profiles, associated with the difference in age (30–34 years old vs. 54–62 years old), menopausal status (premenopausal vs. postmenopausal), and use of hormone replacement therapy (HRT; user vs. nonuser). None of the premenopausal women used hormonal medication while the postmenopausal women were monozygotic (MZ) cotwin pairs of whom the other sister was current HRT user or the other had never used HRT. Label‐free proteomic analyses resulted in the quantification of 797 muscle proteins of which 145 proteins were for the first time associated with female aging using proteomics. Furthermore, we identified 17β‐estradiol as a potential upstream regulator of the observed differences in muscle energy pathways. These findings pinpoint the underlying molecular mechanisms of the metabolic dysfunction accruing upon menopause, thus having implications for understanding the complex functional interactions between female reproductive hormones and health. 相似文献
98.
The cyclic alternating pattern (CAP), that is, cyclic variation of brain activity within non-REM sleep stages, is related to sleep instability and preservation, as well as consolidation of learning. Unlike the well-known electrical activity of CAP, its cerebral hemodynamic counterpart has not been assessed in healthy subjects so far. We recorded scalp and cortical hemodynamics with near-infrared spectroscopy on the forehead and systemic hemodynamics (heart rate and amplitude of the photoplethysmograph) with a finger pulse oximeter during 23 nights in 11 subjects. Electrical CAP activity was recorded with a polysomnogram. CAP was related to changes in scalp, cortical, and systemic hemodynamic signals that resembled the ones seen in arousal. Due to their repetitive nature, CAP sequences manifested as low- and very-low-frequency oscillations in the hemodynamic signals. The subtype A3+B showed the strongest hemodynamic changes. A transient hypoxia occurred during CAP cycles, suggesting that an increased CAP rate, especially with the subtype A3+B, which may result from diseases or fragmented sleep, might have an adverse effect on the cerebral vasculature. 相似文献
99.
Jaakko Patrakka Karl Tryggvason 《Biochemical and biophysical research communications》2010,396(1):164-69
The glomerular filtration barrier is composed of glomerular endothelial cells, the glomerulus basement membrane and the podocyte cell layer. The filtration barrier is a target of injury in several systemic and renal diseases, and this often leads to progressive renal disease and kidney failure. Therefore, it is essential to understand the molecular biology of the glomerulus. During the last two decades, a lot of new information about molecular components of the glomerulus filtration barrier has been generated. Many of the key discoveries have been obtained through studies on the genetic background of inherited glomerular diseases. These studies have emphasized the role of podocytes in the filtration barrier function. During the last decade, the use of knockout mouse technology has become more available and given important new insights into the functional significance of glomerular components. Large-scale approaches, such as microarray profiling, have also given data about molecules involved in the biology and pathology of the glomerulus. In the coming decade, the use of global expression profiling platforms, transgenic mouse lines, and other in vivo gene delivery methods will rapidly expand our understanding of biology and pathology of the glomerular filtration barrier, and hopefully expose novel target molecules for therapy in progressive renal diseases. 相似文献
100.
Jaakko L.O. Pohjoismäki J. Bradley Holmes Stuart R. Wood Takehiro Yasukawa Aurelio Reyes Tricia J. Cluett Smaranda Willcox Andrew P. Jackson Jack D. Griffith Howard T. Jacobs 《Journal of molecular biology》2010,397(5):1144-1155
We demonstrate, using transmission electron microscopy and immunopurification with an antibody specific for RNA/DNA hybrid, that intact mitochondrial DNA replication intermediates are essentially duplex throughout their length but contain extensive RNA tracts on one strand. However, the extent of preservation of RNA in such molecules is highly dependent on the preparative method used. These findings strongly support the strand-coupled model of mitochondrial DNA replication involving RNA incorporation throughout the lagging strand. 相似文献