Functions tissue distribution

AdCy Effect of Gaj Effect of gpy Effects of Ca2+and/or calmodulin Effects of protein kinases Tissue distribution Physiological functions... 

Satake H, Kawada T (2006) Overview of the primary structure, tissue distribution, and function of tachykinins and their receptors. Curr Drug Targets 7 963-974... 

Chronic liposome administration in mice Effects on reticuloendothelial function and tissue distribution, J. Pharmacol. Exp. Ther.. 229, 267-275. 

All the actual or putative functional benefits of carotenoids are dependent on their bioavailability amounts consumed, amounts released from the food structure during digestion and extent of absorption and tissue distribution. The following three sections deal with each of these issues in turn. 

In this chapter we will review the recent investigations of the structure of both the a and P subunit, and the function of gastric H,K-ATPase. We will proceed from a brief overview of the tissue distribution to a successive discussion of structure, kinetics, transport properties, lipid dependency, solubilization and reconstitution, and inhibitors of H,K-ATPase that may label functionally important domains of the enzyme. 

In mammals, as in yeast, several different metallothionein isoforms are known, each with a particular tissue distribution (Vasak and Hasler, 2000). Their synthesis is regulated at the level of transcription not only by copper (as well as the other divalent metal ions cadmium, mercury and zinc) but also by hormones, notably steroid hormones, that affect cellular differentiation. Intracellular copper accumulates in metallothionein in copper overload diseases, such as Wilson s disease, forming two distinct molecular forms one with 12 Cu(I) equivalents bound, in which all 20 thiolate ligands of the protein participate in metal binding the other with eight Cu(I)/ metallothionein a molecules, with between 12-14 cysteines involved in Cu(I) coordination (Pountney et ah, 1994). Although the role of specific metallothionein isoforms in zinc homeostasis and apoptosis is established, its primary function in copper metabolism remains enigmatic (Vasak and Hasler, 2000). 

Wu, X., et al. Structural and functional characteristics and tissue distribution pattern of rat OCTN1, an organic cation transporter, cloned from placenta. Biochim. Biophys. Acta 2000, 1466, 315-327. 

The tissue distribution of P-glycoprotein yields important clues to its function. In most tissues it is localized to the apical (luminal) membrane of polarized epithelial cell layers. This location suggests that P-glycoprotein extrudes its substrates from the epithelial cells into the adjacent lumen. It is anticipated that P-glycopro-tein plays an important role as a protective mechanism against naturally occur-... 

Breast Cancer Resistance Protein (BCRP, also known as MXR or ABCP), first cloned from mitoxantrone and anthracycline-resistant breast and colon cancer cells [188, 189] is a half-transporter efflux pump believed to function as a homo-or hetero-dimer. Following its identification, BCRP-mediated drug resistance was observed for topoisomerase inhibitors including camptothecins [190, 191] and in-dolocarbazoles [192]. In normal tissues, BCRP was detected in placental syncytio-trophoblasts, hepatocyte canalicular membrane, apical intestinal epithelia and vascular endothelial cells [193]. These findings support the important role BCRP plays in modulating topotecan bioavailability, fetal exposure and hepatic elimination [194]. Considering that the substrates and tissue distributions for BCRP overlap somewhat with MDR1 and MRPs [195], additional studies will be required to define the relative contribution of each of these transporters in the overall and tis-... 

The three class I ADH promoters are very similar. Prominent among the ds-act-ing elements that contribute to promoter function are the TATA box, a pair of C/ EBP sites (that can also be bound by DBP) flanking the TATA box, an E-box sequence (CACGTG) just upstream at which USF can bind, and a G3T sequence (that binds Spl) one helical turn further upstream from the E-box [28, 29]. Further upstream are CTF/NF-1 and HNF-1 sites, and some elements that are specific to only some of these genes [24]. Differences among the class I genes in these and other sites affect the tissue distribution and amount of expression. Sequence differences among individuals could well affect the level and site(s) of expression, and thereby the effects of alcohol. 

Thiolactomycin (16) is another natural product that reversibly inhibits E. coli FabF, FabB, and FabH with respective ICso s of 6, 25 and 110 (iM. Unlike cerulenin, it binds the malonyl-ACP site of the enzyme [27]. Despite modest double-digit MICs on . coli, S. aureus, Serratia marces-cens, and Mycobacterium tuberculosis, 16 has generated quite some interest due to its good in vivo protection against an oral or intramuscular S. marcescens urinary tract infection model where it displayed rapid tissue distribution [28]. Despite several medicinal chemistry efforts, thiolactomycin has proven difficult to optimize due to some strict functional group requirements for its SAR [29]. 

T. Terada, S. Masuda, J. Asaka, M. Tsuda, T. Katsura, and K. Inui. Molecular cloning, functional characterization and tissue distribution of rat H+/organic cation antiporter MATE1. Pharm Res 23 1696-1701 (2006). 

The distinguishing structural and functional protein for caveolae is caveolin. Caveolin proteins display properties that are likely involved in the distinguishing morphology of caveolae. Caveolins have a high affinity for both cholesterol and sphingolipids coupled with 3 carboxy-terminal palmitoylated cysteine residues. Three isoforms of caveolin exist and show distinct tissue distribution. Likely because it was discovered first and is perhaps most abundant, caveolin-1 has garnered the lion s share of research attention. 

Since numerous DUBs are present in eukaryotic organisms (Table 2), it is probable that they possess substrate specificity. UCHs have been studied in some detail with respect to their substrate specificity. Two major UCHs in mammals are UCH-Ll and UCH-L3. Larsen et al showed that UCH-Ll cleaves linear polyubiquitin molecules more efficiently than UCH-L3. In contrast, UCH-L3 appears to prefer ubiquitin fused to small ribosomal proteins (see Figure 7). The tissue distribution of the two UCHs is indicative of their functional specialization as well. UCH-Ll is a neuronal-specific enzyme whereas UCH-L3 is expressed primarily in hematopoietic tissues. Another UCH called UCH-L2 has wide tissue distribution. ... 

To Study interactions between proteins and drugs, an available tool is the Drug Absorption, Distribution, Metabolism, and Excretion (ADME) Associated Protein Database (see Table 1.5). The database contains information about relevant proteins, functions, similarities, substrates and hgands, tissue distributions, and other features of targets. Eor the understanding of pharmacokinetic (PK) and pharmacodynamic (PD) features, some available resources are listed in Table 1.5. For example, the Pharmacokinetic and Pharmacodynamic Resources site provides links to relevant software, courses, textbooks, and journals (see Note 5). For quantitative structure-activity relationship (QSAR), the QSAR Datasets site collects data sets that are available in a structural format (see Table 1.5). 

E.J. Knust, C. Mueller-Platz, M. Schueller, Synthesis, quality control and tissue distribution of 2-[ F]nicotinic acid diethylamide, a potential agent for regional cerebral function studies, J. Radioanal. Chem. 74 (1982) 283-291. 

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