Kidney mitochondria

Aminophenol is a selective nephrotoxic agent and intermpts proximal tubular function (121,122). Disagreement exists concerning the nephrotoxity of the other isomers although they are not as potent as 4-aminophenol (123,124). Respiration, oxidative phosphorylation, and ATPase activity are inhibited in rat kidney mitochondria (125). The aminophenols and their derivatives are inhibitors of 5-Hpoxygenase (126) and prostaglandin synthetase... 

Hydroxy vitamin D pools ia the blood and is transported on DBF to the kidney, where further hydroxylation takes place at C-1 or C-24 ia response to calcium levels. l-Hydroxylation occurs primarily ia the kidney mitochondria and is cataly2ed by a mixed-function monooxygenase with a specific cytochrome P-450 (52,179,180). 1 a- and 24-Hydroxylation of 25-hydroxycholecalciferol has also been shown to take place ia the placenta of pregnant mammals and ia bone cells, as well as ia the epidermis. Low phosphate levels also stimulate 1,25-dihydtoxycholecalciferol production, which ia turn stimulates intestinal calcium as well as phosphoms absorption. It also mobilizes these minerals from bone and decreases their kidney excretion. Together with PTH, calcitriol also stimulates renal reabsorption of the calcium and phosphoms by the proximal tubules (51,141,181—183). 

Fig. 6.8 Electron photomicrograph of mouse kidney mitochondria. The structure of both the cytoplasmatic membrane (centre) and the mitochondrial membranes is visible on the ultrathin section. Magnification 70,000x. (By courtesy of J. Ludvik)... 

The active forms of the D vitamins are la,25-dihydroxy-vitamin Dj and 25-hydroxy-vitamin Dj. They are formed by enzymatic hydroxylation in the liver microsomes and then in the kidney mitochondria by a ferredoxin flavoprotein and cytochrome P-450. The 1,25-dihydroxy vitamin is then transported to the bone, intestine, and other target organs (kidneys, parathyroid gland). Consequently, it can be considered a hormone since it is produced in one organ but used elsewhere. It mobilizes calcium and phosphate and also influences the absorption of these ions in the intestine, thus promoting bone mineralization. The hormone is also active in relieving hypoparathyroidism and postmenopausal osteoporosis, which, for example, results in the brittle bones of elderly women. 

Glutamic acid, Lysine, Tyrosine Escherichia coli, Bacillus subtilus, Aeromonas phenologenes, Porcine kidney mitochondria, Sugar beet 74, 75,76,77, 78,79... 

Attempts to demonstrate 25-hydroxy-vitamin D3-l-hydroxylase activity in vitro with rat kidney homogenates have been unsuccessful, although chick kidney preparations exhibit such activity. A heat-labile and very potent inhibitor of the hydroxylase has now been found in the rat preparation 322 all fractions of the kidney homogenate contained the factor, but the microsomes were the richest source, and they released the inhibitor during incubation. A similar inhibitor is also present in rat intestine and serum and in pig kidney, and it may well play a regulatory role in the synthesis of 1,25-dihydroxy-vitamin D3.323 Direct spectroscopic and inhibitory evidence for the presence of cytochrome P450 in kidney mitochondria and of its... 

The assay was used to measure enzyme activity in dialyzed cytosolic fractions from rat kidney (protein concentration 2 mg/mL) and in rat kidney mitochondria (protein concentration 3 mg/mL). 

Soluble D-lactate dehydrogenases with enzymic properties similar to those of the D-2-hydroxyacid dehydrogenase of anaerobic yeast have been isolated from rabbit kidney mitochondria (333-334) and from a species of Mycohacterium (335). It is not clear whether these enzymes are metal-containing flavoproteins. 

The effect of external pH on glutamate efflux has also been studied in both liver and kidney mitochondria [103,104]. External protons decrease the of efflux without altering the of matrix glutamate. If protons are viewed as preventing the... 

Studies performed by the authors of this review [142,144], suggest that the discrepancies are due to functional microcompartmentation between the aspartate aminotransferase and the aspartate transporter. The apparent for aspartate efflux can be dramatically decreased by generation of intramitochondrial aspartate by the aminotransferase reaction. Detailed isotopic studies using labelled matrix aspartate in liver mitochondrial [142] and labelled intramitochondrial glutamate in kidney mitochondria [144] confirmed the initial suggestion. 

Santos NA, Catao CS, Martins NM, Curti C, Bianchi ML, Santos AC Cisplatin-induced nephrotoxicity is associated with oxidative stress, redox state unbalance, impairment of energetic metabolism and apoptosis in rat kidney mitochondria Arch Toxicol 2007 Jul 81 (7) 495-504. 

Lee SH, Yoon YC, Jang YY, Song JH, Han ES, Lee CS. Effect of iron and ascorbate on cyclosporine-induced oxidative damage of kidney mitochondria and microsomes. Pharmacol Res 2001 43 161-171. 

Lund BO, Miller DM, Woods JS. 1991. Mercury-induced hydrogen peroxide production and lipid peroxidation in vitro in rat kidney mitochondria. Biochem Pharmacol 42, (Suppl) S181-S187. 

Schlegel, J., Meier, P., Kass, G. E. N Richter, C. (1991). Inhibition by cyclosporine A of the prooxidant-induced but not of the sodium-induced calcium release from rat kidney mitochondria. Biochem. Pharmacol. 42, 2193-2198. 

As discussed earlier, vitamin D is an important hormone. A critical step in activation is la-hydroxylation (Figure 10.16). Early work established the P450 nature of the enzjnne, localized in kidney mitochondria . Subsequent work demonstrated that the la- and 24-hydroxylation activities could be attributed to different... 

PTH has stimulatory effects on bone and kidney, including the stimulation of la-hydroxylase activity in kidney mitochondria leading to the increased production of the biologically active hormone 1,25-dihydroxyvitamin D (calcitriol) from 25-hydroxyvitamin D (see Figure 61-5). Solid lines indicate a positive effect dashed lines refer to negative feedback. 

Throughout the course of work on the vitamin D3 metabolism, parallel work has occasionally been carried out with the vitamin D2 series. 25-OH-D2 has also been isolated and chemically identified ° Furthermore, 1,25-(OH)2D2 has been prepared in vitro with chick kidney mitochondria and its structure unequivocally elud-dated" The biological activity of the vitamin D2 compounds has been assessed in the rat and found to be identical in every respect to the vitamin D3 compounds. In the bird, however, as described above, the vitamin D2 compounds, including 1,25-(0H)2D2, are approximately 1/5 to 1/10 as active as their vitamin D3 counterparts Of some interest is that Upjohn chemists have successfully synthesized the 25-OH-D2 and the 25-OH-24-epiD2. The 25-OH-24-epiD2 much less active than 25-OH-D2 (J. A. Campbell, L. Reeve and H. F. DeLuca, unpublished results). 

This system is found in kidney mitochondria and is absent in vitamin D-deficient tissue " It is regulated by vitamin D and parathyroid hormone Little is known beyond these facts except an extra-renal site of 26-hydroxylation is known. 

Mingatto FE, Santos AC, Uyemura SA, Jordani MC, Curti C (1996) In vitro interaction of nonsteroidal anti-inflammatory drugs on oxidative phosphorylation of rat kidney mitochondria respiration and ATP synthesis. Arch Biochem Biophys 334(2) 303-308 Mingatto FE, Rodrigues T, Pigoso AA, Uyemura SA, Curti C, Santos AC (2002) The critical role of mitochondrial energetic impairment in the toxicity of nimesulide to hepatocytes. J Pharmacol Exp Ther 303 (2) 601-607... 

PEPCK Liver, kidney Mitochondria 75 kDa Mn (cofactor) Mainly Iactate->glucose... 

Pyruvate Liver, kidney Mitochondria monomer Tetramer K, Mg, acetylCoA acids to glucose... 

Johnson, D. Lardy, H. (1967) Isolation of liver or kidney mitochondria. Methods Emymol 10, 94-96. Parsons, D.F., Williams, G.R. Chance, B. (1966) Characteristics of isolated and purified preparations of the outer and inner membranes of mitochondria. Ann. New. York. Acad. Sci. 137, 643-666. 

Ishikawa, E., Oliver, R. Reed, L. (1966) Proc. Natl. Acad. Sci. 56, 534-541. Alpha-Keto acid dehydrogenase complexes, V. Macromolecular organization of pyruvate and alpha-ketoglutarate dehydrogenase complexes isolated from beef kidney mitochondria. 

Zetterstrom (1951a) observed an appreciable effect of the phosphoryl-ated vitamin D2 on the activity of purified kidney phosphatase. He also (1951b) postulated a stimulating effect of the phosphorylated vitamin D on kidney mitochondria. It would, however, seem that he worked with a system of very low activity. 

Vasington FD, Murphy JV (1962) Ca " uptake by rat kidney mitochondria and its dependence on respiration and phosphorylation. J Biol Chem 237 2670-2677... 

Sareosina, N-methyl0etne CH3-NH-CH2-COOH, an intermediate in the metabolism of choline in liver and kidney mitochondria (see One-carbon cycle). It has also been isolated from starfish and sea urchins where it appears to be a major metabolite. 

Pedersen JI, Shobaki HH, Holmberg I, Bergseth S, Bjdrkhem I (1983) 25-hydroxyvitamin Dj-24-hy-droxylasein rat kidney mitochondria. J Biol Chem 258 742-746... 

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