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Enzymes : a very short introduction
\"Enzymes are the astonishing, tiny molecular machines that make life possible. Each one of these small proteins speeds up a single chemical reaction inside a living organism many millionfold. Working together, teams of enzymes carry out all the processes that collectively we recognise as life, from making DNA to digesting food. This Very Short Introduction explains the why and the how of speeding up these reactions - catalysis - before going on to reveal how we have evolved these catalysts of such extraordinary power and exquisite selectivity. Paul Engel shows how X-ray crystallography has revealed the complex molecular shapes that allow enzymes to function at an extraordinarily sophisticated level. He also examines medical aspects of enzymes, both in the way faulty enzymes cause disease and in the way enzymes can be used for diagnosis and therapy. Finally, he looks at the many varied ways in which individual enzymes, taken out of their biological context, are used nowadays as tools - in washing powders, food production, waste treatment, and chemical synthesis.\"--Amazon.ca
Book
Effect of Ginkgo biloba special extract EGb 761® on human cytochrome P450 activity: a cocktail interaction study in healthy volunteers
Purpose
We assessed the human in vivo metabolic drug interaction profile of
Ginkgo biloba
extract EGb 761® with respect to the activities of major cytochrome P450 (CYP) enzymes.
Methods
A single-center, open-label, randomized, three-fold crossover, cocktail phenotyping design was applied. In random order, the following treatments were administered to 18 healthy men and women for 8 days each: placebo twice daily, EGb 761® 120 mg twice daily, and EGb 761® 240 mg in the morning and placebo in the evening. In the morning of day 8, administration was performed together with the orally administered phenotyping cocktail (enzyme, metric): 150 mg caffeine (CYP1A2, paraxanthine/caffeine plasma ratio 6-h postdose), 125 mg tolbutamide (CYP2C9, plasma concentration 24-h postdose), 20 mg omeprazole (CYP2C19, omeprazole/5-hydroxy omeprazole plasma ratio 3-h postdose), 30 mg dextromethorphan (CYP2D6, dextromethorphan/dextrorphan plasma ratio 3-h postdose), and 2 mg of midazolam (CYP3A, plasma concentration 6-h postdose). Formally, absence of a relevant interaction was assumed if the 90% confidence intervals (CIs) for EGb 761®/placebo ratios of the metrics were within the 0.70–1.43 range.
Results
EGb 761®/placebo ratios for phenotyping metrics were close to unity for all CYPs. Furthermore, respective CIs were within the specified margins for all ratios except CYP2C19 for EGb 761® 120 mg twice daily (90% CI 0.681–1.122) and for CYP2D6 for EGb 761® 240 mg once daily (90% CI 0.667–1.281). These findings were attributed to the intraindividual variability of the metrics used. All treatments were well tolerated.
Conclusion
EGb 761® has no relevant effect on the in vivo activity of the major CYP enzymes in humans and therefore has no relevant potential to cause respective metabolic drug–drug interactions.
Journal Article
Randomized Trial of Verubecestat for Prodromal Alzheimer’s Disease
In a randomized trial, patients with brain amyloid deposition but no dementia who received a β-site amyloid precursor protein–cleaving enzyme 1 inhibitor had no benefit with respect to clinical outcomes and worsening on some measures of cognition and daily function.
Journal Article
Correction: Hu et al. Dynamics of Nanomotors Propelled by Enzyme Cascade Reactions. Int. J. Mol. Sci. 2024, 25, 12586
There was an error in the original publication [...]
Journal Article
Statistical Optimization of alpha-Amylase Production from Novel Local Isolated Bacillus spp. NRC1 and Its Textile Applications
By employing Plackett-Burman design (PBD) to investigate the qualitative interactions between eleven parameters [potato shell weight, incubation time, glucose, lactose, baker's yeast, peptone, (NH.sub.4).sub.2SO.sub.4, CuSO.sub.4, FeSO.sub.4, CaCl.sub.2, KCl], and central composite design (CCD), the production of [alpha]-amylase by a local bacterial isolate Bacillus spp. NRC1 using agro-industrial wastes was improved. Using a variety of waste materials, including corn cobs (CC), onion peels (OP), rice straw (RS), potato shells (PS), Molokhia stem (MS), okra suppression (OS), lemon peels (LP), and pea peels (PP), Bacillus spp. NRC1 was tested in the production of amylase. Out of the eight agro-industrial wastes tried, the highest amylase yield (6.99 U/ml) was reached using potato peels. The statistical optimization of enzyme production was carried out using PBD followed by CCD design, causing 2.06-fold and 1.51-fold increase, respectively. The overall increase was 3.11-fold. In PBD design, potato peels, peptone and (NH.sub.4).sub.2SO.sub.4 were positive factors for amylase production. The crude enzyme was tested for its ability to desize cotton fabric and subsequently studying its effect on fabric dyeability. The produced amylase proved its potentials in textile industry.
Journal Article
Cape Gooseberry —Selected Aspects
Vacuum-Assisted Sorbent Extraction (VASE) is a novel extraction technique that uses vacuum to facilitate the transfer of volatile compounds from the matrix to the sorbent. This technique was explored for extraction of volatiles from cape gooseberry fruit, for both qualitative and quantitative analyses. Selected extraction parameters were tested: sample size, extraction temperature and time, influence of tissue disintegration on release of volatiles, and also addition of Ag[sup.+1] ions in the form of AgNO[sub.3] to stop enzymatic formation of volatile compounds. For selected conditions (10 g sample, extraction for 30 min. at 40 °C of volatiles from blended fruit) quantitative aspects were explored. Twenty-two compounds of cape gooseberry were tested. The method was characterized with a very good linearity in a range of 10–5000 µg/kg and good reproducibility. The experiments proved the usefulness of VASE in both volatile profiling and quantitative analyses of cape gooseberry and in prospective other fruit.
Journal Article
Soil enzymology: classical and molecular approaches
It is still problematic to use enzyme activities as indicators of soil functions because: (1) enzyme assays determine potential and not real enzyme activities; (2) the meaning of measured enzyme activities is not known; (3) the assumption that a single enzyme activity is an indicator of nutrient dynamics in soil neglects that the many enzyme activities are involved in such dynamic processes; (4) spatio-temporal variations in natural environments are not always considered when measuring enzyme activities; and (5) many direct and indirect effects make difficult the interpretation of the response of the enzyme activity to perturbations, changes in the soil management, changes in the plant cover of soil, etc. This is the first review discussing the links between enzyme-encoding genes and the relative enzyme activity of soil. By combining measurements of enzyme activity in soil with expression (transcriptomics and proteomics) of genes, encoding the relative enzymes may contribute to understanding the mode and timing of microbial communities’ responses to substrate availability and persistence and stabilization of enzymes in the soil.
Journal Article
Efficacy and Safety of Nintedanib in Idiopathic Pulmonary Fibrosis
In this randomized, placebo-controlled trial, treatment with nintedanib, an intracellular inhibitor of multiple tyrosine kinases, led to a reduced rate of loss of forced vital capacity in patients with idiopathic pulmonary fibrosis.
Idiopathic pulmonary fibrosis is a fatal lung disease characterized by worsening dyspnea and progressive loss of lung function.
1
A decline in forced vital capacity (FVC) is consistent with disease progression and is predictive of reduced survival time.
1
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6
Idiopathic pulmonary fibrosis is believed to arise from an aberrant proliferation of fibrous tissue and tissue remodeling due to the abnormal function and signaling of alveolar epithelial cells and interstitial fibroblasts.
7
The activation of cell-signaling pathways through tyrosine kinases such as vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and platelet-derived growth factor (PDGF) has been implicated in the pathogenesis of . . .
Journal Article
Single-Agent Divarasib (GDC-6036) in Solid Tumors with a KRAS G12C Mutation
Among patients with cancers bearing the
KRAS
G12C mutation who received divarasib at a 400-mg dose, 56% with lung cancer, 36% with colorectal cancer, and 36% with other tumor types had a confirmed response.
Journal Article