Protein activities, distribution

The coupling of the GPC spin column/ESI-MS screening results with NMR (2D HSQC) is a powerful method for confirming that the non-covalent binders identified by the MS experiments truly bind at the predicted active site by observing NMR chemical shift perturbations in the vicinity of the protein active site [1, 15]. In contrast, the absence of chemical shift perturbations or a random distribution of chemical shift changes on the protein surface would imply a lack of an interaction of the compound with the protein or potentially the existence of non-specific binding. The development of the GPC spin column/MS/NMR assay... 

Albendazole is a benzimidazole carbamate. After oral administration, it is erratically absorbed (increased with a fatty meal) and then rapidly undergoes first-pass metabolism in the liver to the active metabolite albendazole sulfoxide. It reaches variable maximum plasma concentrations about 3 hours after a 400-mg oral dose, and its plasma half-life is 8-12 hours. The sulfoxide is mostly protein-bound, distributes well to tissues, and enters bile, cerebrospinal fluid, and hydatid cysts. Albendazole metabolites are excreted in the urine. 

A detailed analysis of the effect of the mutational load on the distribution of protein activity within a mutant population has been carried out... 

Copper is an essential element to most life forms. In humans it is the third most abundant trace element only iron and zinc are present in higher quantity. Utilization of copper usually involves a protein active site which catalyzes a critical oxidation reaction, e.g., cytochrome oxidase, amine oxidases, superoxide dismutase, ferroxidases, dopamine-/ -hydrox-ylase, and tyrosinase. Accordingly, animals exhibit unique homeostatic mechanisms for the absorption, distribution, utilization, and excretion of copper (J). Moreover, at least two potentially lethal inherited diseases of copper metabolism are known Wilson s Disease and Menkes s Kinky Hair Syndrome (I). 

In this chapter, we undertake a review of the quantitative aspects of dopamine neurotransmission of relevance to the spatial and temporal specificity of the dopamine signal. The kinetics of dopamine release and clearance are considered in order to estimate the temporal and spatial concentration distribution of dopamine. The location of receptors and their sensitivity to dopamine are taken into account. We then consider the regulation of ion channels by the G proteins activated by dopamine, and how this might explain the effects of dopamine on the whole cell. Finally, we consider the regulation by dopamine of corticostriatal inputs to the spiny cells. 

The relationship between the structure of the peptide environment and active site chemical properties is thus of considerable interest and to a large extent awaits future studies. In this article, some examples of such specific relationships are described, particularly in the case of iron-sulfur proteins, because this class of proteins is distributed widely in living organisms ranging from bacterial cells to mammals. The major function of the proteins is now known to be electron transfer and the... 

H. Biich, J. Knabe, W. Buzeilo, and W. Rummel, StereospeciRcity of anaesthetic activity, distribution, inactivation and protein binding of the optical antipodes of two W-methylated barbiturates, /. Pharmacol. Exp. Then, 175 709 (1970). 

The fact that animals do not need to eat continuously throughout the course of the day indicates that chylomicrons are not necessarily actively distributing nutrients during the entire day Free fatty acids ate supplied to tissues via the chylomicrons, but also from the adipose tissue, which supplies energy to the body throughout the day. The dry matter of adipose tissue consists of 5% protein and over 90% lipids. About 95% of the lipids ate TGs the nest consists of 1-2% diglycerides, 0-25% phospholipids, and 0.25% cholesterol- Adipose tissue may contain 5-30% water by weight-... 

Isepamicin is given intravenously or intramuscularly in a dosage of 15 mg/kg/day or 7.5 mg/kg bd. It is not bound to plasma proteins, it distributes in extracellular fluids, and it enters some cells (outer hair cells, kidney cortex) by an active transport mechanism (1) the transference of isepamicin to the bone marrow is excellent (3). Isepamicin is not metabolized and is renally excreted with a half-life of 2-3 hours in adults with normal renal function. Its clearance is reduced in neonates, and a dose of 7.5 mg/kg/day is recommended in children younger than 16 days. Its clearance is also reduced in elderly people, but no dosage adjustment is required. In patients with chronic renal impairment, isepamicin clearance is proportional to creatinine clearance. 

Schneider M, Verges B, Klein A, Miller ER, Decker V, Desrumaux C, Masson D, Gambert P, Brun JM, Fruchart-Najib J, Blache D, Witztum JL, Lagrost L. Alterations in plasma vitamin E distribution in type 2 diabetic patients with elevated plasma phospholipid transfer protein activity. Diabetes 2004 53(10) 2633-9. 

Ciprofloxacin is well absorbed in the gastrointestinal tract. Serum concentration peaks in 1.5-2 h postingestion. The elimination half-life with normal renal function is 4h. Ciprofloxacin is 20-40% bound to serum proteins and distributed widely throughout the body. Four metabolites in human urine have been identified, which account for 15% of an oral dose. The metabolites have antimicrobial activity, which are less active than the parent compound of ciprofloxacin. Ciprofloxacin inhibits CYP3A4 enzyme system. 

Darmani NA, Sim-Selley LJ, Martin BR, Janoyan JJ, Crim JL, Parekh B, Breivogel CS (2003b) Antiemetic and motor-depressive actions of CP55,940 cannabinoid CBl receptor characterization, distribution, and G- protein activation. Eur J Pharmacol 459 83-95... 

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