Production mitochondrial activity

Numerous studies have demonstrated that degradation products of (3-carotene exhibit deleterious effects in cellular systems (Alija et al., 2004, 2006 Hurst et al., 2005 Salerno et al., 2005 Siems et al., 2003). A mixture of (3-carotene degradation products exerts pro-apoptotic effects and cytotoxicity to human neutrophils (Salerno et al., 2005 Siems et al., 2003), and enhances the geno-toxic effects of oxidative stress in primary rat hepatocytes (Alija et al., 2004, 2006), as well as dramatically reduces mitochondrial activity in a human leukaemic cell line, K562, and RPE 28 SV4 cell line derived from stably transformed fetal human retinal pigmented epithelial cells (Hurst et al., 2005). As a result of degradation or enzymatic cleavage of (3-carotene, retinoids are formed, which are powerful modulators of cell proliferation, differentiation, and apoptosis (Blomhoff and Blomhoff, 2006). 

As mentioned previously, P-carotene oxidation products substantially reduce mitochondrial activity in an RPE cell line, 28 SV4, derived from fetal human RPE cells (Hurst et al., 2005). In these experiments P-carotene was degraded in dichloromethane/methanol/water solution by hypochlorite, NaOCl. Exposure of the 28 SV4 cells to a mixture of the degradation products corresponding... 

A number of studies have reported that the MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) in vitro cytotoxicity assay is a convenient method for assessing ceU viability. The main features found with this assay are its ease of use, accuracy and rapid indication of toxicity. This method is of interest particularly when exposure to unknown chemical substances requires the rapid detection and evaluation of toxic effects. Direct comparisons of the IC50 value determined in the MTS assay and in vivo cytotoxicity showed a significant, direct correlation. The highest correlation was found when the MTS assay was compared with test systems using human cell hnes. The MTS assay is based on the conversion of a tetrazolium salt into a colored, water-soluble formazan product by mitochondrial activity of viable cells at 37 °C. The amount of formazan produced by dehydrogenase enzymes is directly proportional to the number of living cells in culture and can be measured at 492 nm. 

Zhang et al. [602] investigated the effects of icariin (ICA) on the content of Ap and the expression of neurotrophic factors in the brain of mitochondrial deficiency model rats. Chronic infusion of sodium azide by minipump induced a decrease in the activity of mitochondrial cytochrome C oxidase, an increase in the content of Ap, and a marked decline in the expression of NGF, BDNF, and its receptor TrkB in the brain of rats. Intragastric administration of ICA ameliorated all these abnormalities in the model rats, increasing mitochondrial activity, inhibiting Ap production, and enhancing the expression of neurotrophic factors in the brain of model rats induced by sodium azide. 

Ammonia is condensed with bicarbonate and ATP in the mitochondrion to form carbamoyl phosphate in a reaction catalyzed by carbamoyl phosphate synthetase I. Two molecules of ATP are used in this reaction one provides the phosphate, and the other is hydrolyzed to ADP and inorganic phosphate (P) to provide the energy that drives the reaction to products. The activated carbamoyl group is then transferred to the amino acid ornithine by the mitochondrial enzyme ornithine transcarbamoylase to form citrulline. Citrulline then is transported out of the mitochondrion to the cytosol, where the rest of the reactions... 

Kunze, B., Jansen, R., Hofle, G., and Reichenbach, H. (2004) Ajudazols, new inhibitors of the mitochondrial electron transport from Chondromyces crocatus. Production, antimicrobial activity and mechanism of action. J. Antibiot, 57 (2), 151-155. 

Aconitase (ACO) is a mitochondrial protein that acts as the second enzyme in the TCA cycle contributing to overall energy production. Aconitase activity is significantly reduced in the striatum and cortex of HD individuals thereby yielding in overall decrease of ATP production (Sorolla et al. 2008). Mitochondrial dysfunction, which is observed in HD, can occur via the oxidative modification of aconitase (Petrozzi et al. 2007). Decreased ATP production due to lipid peroxidation can lead to altered energy metabolism and reduced gluconeogenesis, which have been associated with HD pathogenesis (Josefsen et al. 2010). 

WT gametes have therefore lost their ability to survive in photo-trophic conditions and depend on mitochondrial ATP production. Table I shows that inhibition of mitochondrial activity prior to gametogenesis prevents cyt b6/f disappearance. Cyt b6/f complexes are also maintained in the thylakoid membranes from WT gametes differentiated in darkness and in gametes from PSI mutants. In these cases, both linear and cyclic photosynthetic electron flows are inactive. In contrast, the absence of PSII activity, which preserves cyclic electron flow around PSI, does not prevent cyt b6/f disappearance. Thus both mitochondrial and photosynthetic linear as well as cyclic activities control the presence cyt b6/f complexes in the thylakoid membranes from the gametes. These observations suggest that the rate of ATP synthesis in the gametes is a key factor in this metabolic process. 

Figure 2 Mitochondrial fatty-acid (FA) /3-oxidation pathway. Long-chain fatty acids are activated, converted to carnitine esters, transported across the inner mitochondrial membrane, and re-converted to their CoA thioester once in the mitochondrial matrix. Four sequential mitochondrial enzyme reactions shorten the fatty acyl-CoA (FA-CoA) by two carbon atoms, which are released as acetyl-CoA. The shortened fatty acyl-CoA can undergo additional cycles of degradation until the entire carbon chain has been converted to acetyl-CoA units. FADHa and NADH, produced in reactions 1 and 3, respectively, can enter the electron transport chain for ATP production. Acetyl-CoA enters the tricarboxylic acid (TCA) cycle, yielding additional NADH and FADHa for ATP production. Mitochondrial /3-oxidation is the primary pathway for recovering the energy stored as triacylglycerol or fat .

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