Cytosol kidney

Metallothioneins are a group of small proteins (about 6.5 kDa), found in the cytosol of cells, particularly of liver, kidney, and intestine. They have a high content of cysteine and can bind copper, zinc, cadmium, and mercury. The SH groups of cysteine are involved in binding the metals. Acute intake (eg, by injection) of copper and of certain other metals increases the amount (induction) of these proteins in tissues, as does administration of certain hormones or cytokines. These proteins may function to store the above metals in a nontoxic form and are involved in their overall metaboHsm in the body. Sequestration of copper also diminishes the amount of this metal available to generate free radicals. 

The 25-OH-D Is further metabolized In the kidney to 1,25 dlhydroxycholecalclferol (1,25(OH)2D) which Is considered to be the major physiologically Important, tissue-active metabolite of vitamin D. It circulates In extremely low concentrations (< 100 pg/ml of serum). Assay of 1,25(OH)2D Is extremely tedious. It Is done by competitive binding technique using a combined Intestinal cell cytosol and chromatin binding system, biosynthetic 3h-1,25(OH)2D3 as labeled ligand and synthetic 1,25(0H)2D3 as standard (31). 

Meanwhile we have shown that the excision activation of ICOR channels is due to disinhibition [72]. The respective inhibitor, operationally named cytosolic inhibitor (Cl), is present in the cytosol of placenta trophoblast cells HT29- and Tg4-colonic carcinoma cells and RE cells of normal and CF patients. The molecule has an apparent molecular weight of 700-1 500 Da it is amphiphilic heat stable and not digested by trypsin, proteases, nucleotidases, lipases or amylase [72]. Burc-khardt, Fromter and their collaborators [114] have confirmed our results and extracted a similar or identical Cl from kidney cortex. 

Adenylate kinase (AK) is a ubiquitous monomeric enzyme that catalyzes the interconversion of AMP, ADP, and ATP. This interconversion of the adenine nucleotides seems to be of particular importance in regulating the equilibrium of adenine nucleotides in tissues, especially in red blood cells. AK has three isozymes (AK 1,2, and 3). AK 1 is present in the cytosol of skeletal muscle, brain, and red blood cells, and AK 2 is found in the intermembrane space of mitochondria of liver, kidney, spleen, and heart. AK 3, also called GTP AMP phosphotransferase, exists in the mitochondrial matrix of liver and heart. 

Mistry P, Lucier GW, Fowler BA. 1985. High affinity lead binding proteins from rat kidney cytosol mediate cell-free nuclear translocation of lead. J Pharmacol Exp Ther 232 462-469. 

Mistry P, Mastri C, Fowler BA. 1986. Influence of metal ions on renal cytosolic lead-binding proteins and nuclear uptake of lead in the kidney. Biochem Pharmacol 35 711-713. 

Proulx [30] summarized the published lipid compositions of BBM isolated from epithelial cells from pig, rabbit, mouse and rat small intestines. Table 3.1 shows the lipid make-up for the rat, averaged from five reported studies [30], On a molar basis, cholesterol accounts for about 50% of the total lipid content (37% on a weight basis). Thus, the cholesterol content in BBM is higher than that found in kidney epithelial (MDCK) and brain endothelial cells (Table 3.1). Slightly different BBM lipid distribution was reported by Alcorn et al. [31] here, the outer (luminal) leaflet of the BBM was seen to be rich in sphingomyelin content, while the inner leaflet (cytosol) was rich in PE and PC. Apical (brush border) and basolateral lipids are different in epithelia. The basolateral membrane content (not reported by... 

Witzmann FA et al. Differential expression of cytosolic proteins in the rat kidney cortex and medulla preliminary proteomics. Electrophoresis 1998 19 2491-2497. 

Two distinct classes of mineralocorticoid-binding sites were first described in the rat kidney. High-affinity cytosolic aldosterone-binding sites are termed mineralocorticoid receptors [4]. Lower-affinity aldosterone-binding sites... 

Phosphoenolpyruvate carboxykinase (PEPCK) deficiency is distinctly rare and even more devastating clinically than deficiencies of glucose-6-phosphatase or fructose-1,6-bisphosphatase. PEPCK activity is almost equally distributed between a cytosolic form and a mitochondrial form. These two forms have similar molecular weights but differ by their kinetic and immunochemical properties. The cytosolic activity is responsive to fasting and various hormonal stimuli. Hypoglycemia is severe and intractable in the absence of PEPCK [12]. A young child with cytosolic PEPCK deficiency had severe cerebral atrophy, optic atrophy and fatty infiltration of liver and kidney. 

Lobel, P.B. and H.D. Marshall. 1988. A unique low molecular weight zinc-binding ligand in the kidney cytosol of the mussel Mytilus edulis, and its relationship to the inherent variability of zinc accumulation in this organism. Mar. Biol. 99 101-105. 

Cytosolic CA II is widespread through tissues, the kidney possesses CA IV which is anchored to the cell membrane of the luminal PCT brush border by linkage with a membrane phospholipid, glycosylphosphatidylinositol. Such luminal positioning allows the enzyme to act upon filtered bicarbonate ions as they enter the tubule. 

The intracellular localization of carboxylesterases is predominantly microsomal, the esterases being localized in the endoplasmic reticulum [73] [79] [93], They are either free in the lumen or loosely bound to the inner aspect of the membrane. The carboxylesterases in liver mitochondria are essentially identical to those of the microsomal fraction. In contrast, carboxylesterases of liver lysosomes are different, their isoelectric point being in the acidic range. Carboxylesterase activity is also found in the cytosolic fraction of liver and kidney. It has been suggested that cytosolic carboxylesterases are mere contaminants of the microsomal enzymes, but there is evidence that soluble esterases do not necessarily originate from the endoplasmic reticulum [94], In guinea pig liver, a specific cytosolic esterase has been identified that is capable of hydrolyzing acetylsalicylate and that differs from the microsomal enzyme. Also, microsomal and cytosolic enzymes have different electrophoretic properties [77]. Cytosolic and microsomal esterases in rat small intestinal mucosa are clearly different enzymes, since they hydrolyze rac-oxazepam acetate with opposite enantioselectivity [95], Consequently, studies of hydrolysis in hepatocytes reflect more closely the in vivo hepatic hydrolysis than subcellular fractions, since cytosolic and microsomal esterases can act in parallel. 

Fig. 6.33. The structure of human calcitonin (compare with salmon calcitonin in Fig. 6.22). The descending arrows indicate sites of cleavage in rat liver lysosomal fraction (full arrows) and rat liver and kidney cytosolic fractions (broken arrows). The ascending arrows indicate sites of cleavage by cathepsin B1 (full arrows) and cathepsin D (broken arrows) [149].

In the liver and kidney cytosolic fractions (downward-pointing broken arrows in Fig. 6.33), three positions of initial endoproteolytic cleavage were... 

Meyer RP, Podvinec M, Meyer UA. 2002. Cytochrome P450 CYPlAl accumulates in the cytosol of kidney and brain and is activated by heme. Mol Pharmacol 62 1061-1067. 

MacFarlane M, Foster JR, Gibson GG, et al. 1989. Cysteine conjugate [3-lyase of rat kidney cytosol Characterization, immunocytochemical localization, and correlation with hexachlorobutadiene nephrotoxicity. Toxicol AppI Pharmacol 98 185-197. 

Pratt IS, Lock EA. 1988. Deacetylation and further metabolism of the mercapturic acid of hexachloro-1,3-butadiene by rat kidney cytosol in vitro. Arch Toxicol 62 341-345. 

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