ATPase deficiency

Groups of 20 female Fischer 344 rats, eight weeks of age, were fed a diet containing 0 (control), 0.03, 0.10 or 1.2% di(2-ethylhexyl) phthalate [purity not specified] for two years. Neoplastic nodules or hepatocellular carcinomas were seen in 0/18 control, 1/18 low-dose, 1/19 mid-dose and 6/20 high-dose rats p < 0.01). Di(2-ethylhexyl) phthalate did not induce foci of altered hepatocytes as judged by basophilia, ATPase-deficiency or glucose-6-phosphatase-deficiency (Cattley et al., 1987). 

Di(2-ethylhexyl) phthalate exerted weak promoting activity in weanling female Sprague-Dawley rats after doses of 200 or 500 mg/kg bw, given three times per week by gavage for 11 consecutive weeks after initiation with a single oral dose of 8 mg/kg bw NDEA. Lower doses were ineffective. The incidence of ATPase-deficient foci was enhanced about two-fold compared with rats treated with NDEA alone. The incidence of foci with expression of y-GT was not affected by di(2-ethylhexyl) phthalate treatment (Oesterle Demi, 1988). 

Exposure of rats to 215 000 mg/m vinylidene fluoride for 3.5 h produced no sign of hepatoxicity. However, treatment of rats with Aroclor 1254 on three consecutive days followed by exposure for 6 h to 65 500 mg/ni did produce some hepatotoxicity. No excess ATPase-deficient foci were observed in the livers of Wistar rats that had been exposed from birth to 5200 mg/m for 8 h per day on five days per week for 10-14 weeks (lARC, 1986). 

TaI la, E., de Mendonca, R.L., Degand, I., Coffeau, A. and Chislain, M. (1998) Schistosoma mansoni Ca2+-ATPase SMA2 restores viability to yeast Ca2+-ATPase-deficient strains and functions in calcineurin-mediated Ca2+ tolerance. Journal of Biological Chemistry 273, 27831-27840. 

Hovnanian, A., 2004, Darier s disease from dyskeratosis to endoplasmic reticulum calcium ATPase deficiency. Biochem Biophys Res Commun, 322 1237—44. 

Although, as indicated above, ethanol could promote the development of PHC by several mechanisms, no animal study has yet revealed an effect of chronic ethanol consumption on the post-initiation phase. Schwarz et al. (1983) administered diethylnitrosamine (3 mg/kg) to female Wistar rats and, after the animals had been allowed to recover from the toxic effects of the carcinogen, administered ethanol in the drinking water (10% w/v) for 16 weeks. This low dosage had no effect on the number or size of ATPase-deficient foci. 

Corticosterone methyl oxidase II deficiency Costeff optic atrophy syndrome Coupling state defect Creatine deficiency Creatine transporter deficiency Cu-binding P-type ATPase deficiency y-Cystathionase deficiency Cystathionine gamma-lyase deficiency Cystathionine y -synthase deficiency Cystathioninuria... 

As noted above, all S. cerevisiae pleiotropic mutants described so far produce secondary p mutations at very high rates. This problem is easily solved by the use of S. pombe, where several distinct classes of chromosomal pleiotropic respiratory-deficient mutants have been described to date (Table V). Curiously, all pleiotropic strains of S. pombe reported so far are deficient in cytochrome aa and/or cytochrome oxidase. Early reports of additional deficiencies of the respiratory chain were hardly quantitative because of the poor basic knowledge of the respiratory chain in S. pombe and imperfect control of the interference produced by glucose repression. More recent papers report deficiencies in a cytochrome 561.5.Two types of ATPase deficiencies were also reported (a) the total absence or presence in reduced amount, of Dio-9-sensitive ATPase, and (b) the oligomycin-insensitive ATPase. 

The cytochrome and ATPase deficiencies of a particularly stable mutant, M126, obtained by X-ray irradiation has been analyzed in more detail. No reversion to the wild type could be induced—with or without muta-... 

Vanadium. Vanadium is essential in rats and chicks (85,156). Estimated human intake is less than 4 mg/d. In animals, deficiency results in impaired growth, reproduction, and Hpid metaboHsm (157), and altered thyroid peroxidase activities (112). The levels of coen2yme A and coen2yme Q q in rats are reduced and monoamine oxidase activity is increased when rats are given excess vanadium (157). Vanadium may play a role in the regulation of (NaK)—ATPase, phosphoryl transferases, adenylate cyclase, and protein kinases (112). 

Figure 7 Mixld for iron (Fe) deficiency induced changes in root physiology and rhizo-sphere chemistry associated with Fc acquisition in strategy I plants. (Modified froin Ref. 1.) A. Stimulation of proton extru.sion by enhanced activity of the plasnialemma ATPase —> Felll solubilization in the rhizospherc. B. Enhanced exudation of reductanls and chela-tors (carhoxylates. phenolics) mediated by diffusion or anion channels Pe solubilization by Fein complexation and Felll reduction. C. Enhanced activity of plasma membrane (PM)-bound Felll reductase further stimulated by rhizosphere acidificalion (A). Reduction of FolII chelates, liberation of Fell. D. Uptake of Fell by a PM-bound Fell transporter.

In iron-deficient conditions Strategy I plants (Figure 4.1) acidify the soil, through the activation of a specific H+-ATPase (Guerinot and Yi, 1994), increase their reducing capacity at the root plasma membrane, and possibly also release reduc-tants into the rhizosphere/I 11 They also release iron chelators, such as caffeic acid... 

Mutations in one nuclear gene (ATP12), encoding an ATPase assembly protein, have been associated with complex V deficiency in an infant with congenital lactic acidosis and a rapidly fatal disorder affecting brain, liver, heart, and muscle [19]. 

Accumulation/efflux studies can be performed on different cell systems or membrane vesicle preparations. In the accumulation assays, uptake of a probe over time, typically either fluorescent (e.g. calcein-AM (CAM) [25-27]) or radiolabeled, into the cell or membrane vesicles is measured in the presence or absence of a known P-gp inhibitor. As P-gp transports substrates out of the cells, the inhibition of the protein would result in an increase in the amount of the probe in the cell. Accumulation studies in cells that overexpress P-gp can be compared to those obtained in the parental cell line that does not have as high a level of P-gp expression. The probe in the absence of inhibitors shows lower accumulation in P-gp expressing cells than in P-gp deficient cells. Similarly, probe accumulation is increased under conditions where P-gp is inhibited such that the difference in accumulation in P-gp deficient and overexpressing cells, respectively, becomes smaller. Accumulation assays poorly distinguish substrates and inhibitors of P-gp and, as far as transport assays are concerned, are also influenced by a passive diffusion property of molecules [20]. In contrast to transport assays, both accumulation (i.e. calcein-AM assay) and ATPase assays tend to fail in the identification ofrelatively low permeable compounds as P-gp active compounds [20]. 

The red blood cell has no mitochondria and is totally dependent on anaerobic glycolysis for ATP. In pyruvate kinase deficiency, the decrease in ATP causes the erythrocyte to lose its characteristic biconcave shape and signals its destruction in the spleen. In addition, decreased ion pumping by Na /K -ATPase results in loss of ion balance and causes osmotic fragility, leading to swelling and lysis. 

Figure 9.21 The creatine/phosphocreatine shuttle in spermatozoa. This shuttle may not be present in all sperm it will depend upon the distance between the mitochondria and the flagellum. Mitochondria are present in the midpiece just below the head. ATP is required for movement of the flagellum which enables the sperm to swim. Dynein ATPase is the specific motor ATPase, similar to myosin ATPase, that transfers energy from ATP to the flagellum. A deficiency of creatine may explain low sperm motility in some infertile men. CK - creatine kinase. Deficiences of enzymes in the pathway for synthesis of creatine are known to occur (see Appendix 8.3).

Boron also appears to be involved in redox metabolism in cell membranes. Boron deficiency was shown to inhibit membrane H -ATPase isolated from plant roots, and H -ATPase-associated proton secretion is decreased in boron-deficient cell cultures [71]. Other studies show an effect of boron on membrane electron transport reactions and the stimulation of plasma reduced nicotinamide adenine dinucleotide (NADH) oxidase upon addition of boron to cell cultures [72, 73]. NADH oxidase in plasma membrane is believed to play a role in the reduction of ascorbate free radical to ascorbate [74]. One theory proposes that, by stimulating NADH oxidase to keep ascorbate reduced at the cell wall-membrane interface, the presence of boron is important in... 

Hokin-Neaverson M, Jefferson JW Deficient erythrocyte Na,K-ATPase activity in different affective states in bipolar affective states in bipolar affective disorder and normalization by lithium therapy. Neuropsychobiology 22 18-25, 1989a Hokin-Neaverson M, Jefferson JW Erythrocyte sodium pump activity in bipolar affective disorder and other psychiatric disorders. Neuropsychobiology 22 1-7, 1989b... 

M21. Miiller-Hocker, J., Stiinkel, S., Pongratz, D., and Hiibner, G., Focal deficiency of cytochrome-c-oxidase and of mitochondrial ATPase combined with loosely coupled oxidative phosphorylation in the skeletal muscle of a patient with progressive external ophthalmoplegia An enzyme histochemical, immunocytochemical and fine structure study. J. Neurol. Sci. 69, 27-36 (1985). 

---