Mammalian subcellular distribution

Protein kinases differ in their cellular and subcellular distribution, substrate specificity and regulation. These properties determine the functional roles played by the very large number of protein kinases that have been found in mammalian tissues, most of which are known to be expressed in neurons [3]. The major classes of protein serine-threonine kinase in the brain, listed in Table 23-1, are covered in this chapter. The major classes of protein tyrosine kinases in the brain are discussed in Chapter 24. 

Saitou M, ando-Akatsuka Y, Itoh M, Furuse M, Inazawa J, Fujimoto K, and Tsukita, S [1997] Mammalian occludin in epithelial cells its expression and subcellular distribution. Eur J Cell Biol 73 222-231... 

The four forms of hexokinase found in mammalian tissues are but one example of a common biological situation the same reaction catalyzed by two or more different molecular forms of an enzyme. These multiple forms, called isozymes or isoenzymes, may occur in the same species, in the same tissue, or even in the same cell. The different forms of the enzyme generally differ in kinetic or regulatory properties, in the cofactor they use (NADH or NADPH for dehydrogenase isozymes, for example), or in their subcellular distribution (soluble or membrane-bound). Isozymes may have similar, but not identical, amino acid sequences, and in many cases they clearly share a common evolutionary origin. 

Li, Y., Dinsdale. D., and Glynn P., Protein domains, catalytic activity, and subcellular distribution of neuropathy target esterase in Mammalian cells, J. Biol. Chem., 278(10), 8820-8825, 2003. 

Until recently, cholesterol has been known to serve primarily as a precursor in steroid hormone and bile component biosynthesis and as an important structural component of biological membranes in animals [82]. A fourth major function for cholesterol in animals is suggested by its formation of a covalent linkage to amino-terminal Sonic hedgehog fragment and its modulation of spatial and subcellular distribution that affects mammalian patterning activities [79]. 

Matias et al. (2001) detected immunostaining in neural tissue of the leeches H. medicinalis and T. tessulatum using antibodies directed against the FAAH catalytic core (GGSSGGEGALI). The leech enzyme metabolized AEA, but it differed from mammalian FAAH in pH-dependency (optimal activity at pH 7 instead of pH 9 to 10), subcellular distributions (primarily cytosohc fractions instead of... 

Over the past ten years there have been many papers published about mammalian sialidase and a few about avian sialidase. Organellar and subcellular distribution studies have been reported upon, as have substrate specificity, purification, physical properties and possible effects of enzyme action. Much of the work is suggestive but not complete, i.e., characterization of the physical properties such as the kinetic parameters, and Vmaxj has only been done on crude enzyme preparations. Composition, molecular weight, and mechanism of action are not known. 

Wagner, M.C., Barylko, B., Albanesi, J.P. (1992). Tissue distribution and subcellular localization of mammalian myosin I. J. Cell Biol. 119, 163-170. 

The intracellular distribution of a glycosidase in a mammalian tissue can be studied by centrifugal fractionation of a homogenate made in isotonic (0.25 M) sucrose solution. The membranes of subcellular particles are preserved in this medium and, provided that there is no leakage of the enzyme, its partition between the different sizes of particle can be measured. Before the enzyme is assayed, it may be necessary to destroy the structure of the particles, in order to make the enzyme completely accessible to the substrate. 

The above definition of toxicity is concerned with living animals, i.e. in vivo studies. Toxicity can also be measured in vitro using mammalian cell or bacterial cultures or subcellular fractions (e.g. for mechanistic studies). However, such toxicity estimates made in vitro may not always reflect accurately the toxicity of a chemical to mammals since absorption, distribution, metabolism and excretion in vivo can markedly alter the profile of toxicity (82UP10502) (see also Section 1.05.2.6). 

The first of at least 14 serotonin (5-hydroxytryptamine [5-HT]) receptor types currently known to exist in the mammalian central nervous system (CNS) was pharmacologically defined more than 25 yr ago (1,2). Yet, it is only within the last 15 yr, with the cloning and sequencing of these receptors, that it has become possible to visualize their distribution at cellular and subcellular... 

Calmodulin, by contrast, is distributed throughout most, if not all, eukaryotic cells from both animal and plant sources. It has not been reported to exist in bacteria. Calmodulin varies in concentration from tissue to tissue with mammalian brain (4) and testis (5) and the electroplax of Electrophorus electricus (6) possessing particularly high content. While the protein has been found to be predominantly cytoplasmic in subcellular fractionation studies, substantial amounts are particulate-associated as well. Binding of calmodulin to particulate fractions is increased by Ca2+, appears to occur at specific sites (7, 8), and... 

Azoreductase activity (substrate l,2-dimethyl-4-(/ -carboxyphenylazo)-5-hydroxybenzene (CPA) (Hanzel and Carlson 1974) and nitroreductase activity (substrate. 77-nitrobenzoic acid) (Carlson 1972) have been detected in digestive gland of M. mercenaria (Table 12). Their properties were similar to those of mammalian enzyme activities and considered indicative of the existence of two separate enzyme systems. Nitroreductase activity was maximal at 35 to 45 C and pH 6.0, Stimulated by flavin mononucleotide, and inhibited by potassium cyanide and air, but not by SKF-525A or carbon monoxide (cytochrome P-450 inhibitors). Azoreductase activity was similarly stimulated by flavin mononucleotide and inhibited by air, but had a pH optimum of 8.0 activity was higher at 37 C than at 22 °C. Both enzyme activities had cytosolic and microsomal subcellular localizations, viz. activity in nmol min g wet weight (% distribution in brackets)... 

Chandra, S. (2008) Subcellular imaging of RNA distribution and DNA replication in single mammalian cells with SIMS the localization of heat shock induced RNA in relation to the distribution of intranuclear bound calcium. J Microsc, 232, 27-35. 

Fatty acids are oxidized only in the form of fatty a< l-CoA derivatives, and mitochondria from mammalian tissues contain the full equipment of enzymes necessary for the synthesis and the degradation of fatty acyl-CoA. The enzymes involved in the oxidative process are located in the mitochondrial matrix, and the inner mitochondrial membrane sequesters the oxidative process from the rest of these organelles. On the contrary, the fatty acids activating enzymes (thiokinase) seem to be present in different compartments of the mitochondrion and widely distributed among the subcellular fractions. The significance of this may lie in the fact that the conditions required for fatty acyl-CoA oxidation differ from those required for other CoA—SH dependent pathways. 

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