Mitochondrial activity

Mitochondria, nitric oxide synthase and arachidonic acid metabolism are sources of reactive oxygen species during ischemia-reperfusion injury. ROS generation during ischemia-reperfusion may come from several sources, including NOS activity, mitochondrial electron transport, multiple steps in the metabolism of arachidonic... 

Permeability transition pore Opening by reactive oxygen species, reactive nitrogen species, bile adds, ihio crosslinkers, atractyloside, betu-liniate, lonidamidem various anticancer drugs, to collapse mitochondrial membrane potential and activate mitochondrial apoptotic pathway... 

Letai A, Bassik MC, Walensky LD, Sorcinelli MD, Weiler S, Korsmeyer SJ (2002), Distinct BH3 domains either sensitize or activate mitochondrial apoptosis, serving as prototype cancer therapeutics, Cancer Cell 2 183-192. 

Rescues mice from lethal sepsis by supporting mitochondrial energetic metabolism and activating mitochondrial biogenesis [187]... 

Two bursts in the production of acid-soluble PolyPs were shown to occur during the growth of some S. cerevisiae strains on a medium containing glucose and galactose under aerobic conditions (Solimene et al., 1980). The respiratory deficient mutant, however, had only one PolyP burst , which indicated that the accumulation of PolyP produced in the first burst depended on the active mitochondrial function (Solimene et al., 1980). 

In addition, hepatic fatty acid oxidation is also required to sustain gluconeogenesis. These fatty acids may be obtained from exogenous feeding or metabolism of fatty acids released from endogenous lipid stores. (3-Oxidation of fatty acids provides the acetyl-CoA needed to activate mitochondrial pyruvate carboxylase and the NADH used as the substrate in the reaction catalyzed by glyceraldehyde 3-phosphate dehydrogenase in the direction of gluconeogenesis (see Fig. 10-1). 

Vinca species. It occurs in the (-) form vincamone, mp. 173-174°C, [ajp-102° (CHCI3)) in Vinca minor, aitd also as racemate vincanorine, mp. 203-204 °C). Activity Vasodilative, hypotensive effects, as well as bronchoconstrictory activity. On chronic administration of (-)-E. to rats increased enzyme activities (mitochondrial cytochrome oxidase) were measured in rat brains. 

Quant, PA., Tubbs, P.K. Brand, M.D. (1990)i ur. J. Biochem. 187, 169-174. Glucagon activates mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase in vivo by decreasing the extent of succinylation of the enzyme. 

Figme 2. Developmental profile of total human hepatic HMG-CoA synthase Homogenates isolated from postmortem human fresh or frozen liver were assayed spectrophotometrically for total HMG-CoA synthase (inactive + active mitochondrial + cytoplasmic isoenzymes) 1 monitoring the disappearance of acetoacetyl-CoA (AAm3 ,J. Total activity is expressed as mU (mg total protein) mean (4 assays from 1 preparation) or mean (mean of 4 assays from each of a number of preparations from each sample) S.E.M. n = 4 or as indicated next to closed squares. Data taken from Quant et aV ... 

Figure 2. Apoptotic pathways-serine and cysteine proteases. Intrinsic and extrinsic Fas and granzyme B apoptotic pathways that are potentially targeted by Serp-2 and Crm A are illustrated. Staurosporine activates mitochondrial apoptotic pathways, Fas ligand and Granzyme B activate extrinsic apoptotic pathways Camptothecin inhibits topoisomerase and blocks DNA repair.

TMT poisoning leads to apopotic cell death including nuclear fragmentation, chromatin condensation, membrane blebbing, caspase activation, mitochondrial dysfunction, and production of reactive oxygen compounds [60,66-69]. 

Apoptosis can be triggered by mitochondrial damage, which is followed by the release of cytochrome c and the caspase cascade [167], The BAX protein activates mitochondrial release of cytochrome c [168], while Bcl-2 is a mitochondrial protein inhibits the apoptotic process and promotes cell survival [169]. Ji et al. [163] research showed that occur a decrease in mitochondrial Bcl-2 and a markedly increase in mitochondrial level of Bax in the HepG2 cells treated with PA from 200 to 400 mM concentrations. The authors suggest that this mechanism can contribute to NASH and NAFLD installation, and especially may play an important role in the transition from steatosis to steatohepatitis in human. Other studies [170] on the effect of FAs-induced steatosis on cellular apoptosis have demonstrated that palmitic and oleic FA mixtures-induced steatosis is associated with apoptosis in hepatocyte cell cultures. Joshi-Barve s et al. [171] studies also showed that exposure to excess palmitic acid induces apoptosis and lL-8 production in hepatocytes in a relation of dose-dependent and time dependent manner, via activation of c-Jun amino terminal kinase (JNK/AP-1), and nuclear factor kappa B (NF-B) transcription factors for IL-8 expression. 

It differs from the Type I enzyme [81] in that both glutamine and ammonia are substrates, although in animal cells glutamine is probably the physiological substrate. A highly active mitochondrial carbamoyl phosphate synthetase I is essential for the detoxication of ammonia through the urea cycle in mammalian livers. 

The effect of stavudine-based HAART on mitochondrial respiratory transport chain function in CD4-I- peripheral blood lymphocytes has been studied in HTV-positive patients in Australia [73. CD4-I-lymphocytes isolated from asymptomatic stavudine-treated patients had reduced basal mitochondrial oxygen consumption compared with untreated HIV-infected patients and uninfected controls. Cells from the stavudine-treated patients also had reduced maximal oxygen consumption. There were no significant differences in citrate synthase activities, mitochondrial volume, or mitochondrial DNA copy numbers per cell between the groups. These findings support an association between stavudine and mitochondrial dysfunction and suggest that the alteration in function does not solely result from the... 

They also contained 25 % more GSH and demonstrated 70 % greater manganese superoxide dismu-tase activity and a 35% reduction in glutathione peroxidase activity. Mitochondrial generation of H2O2 was increased by 200 % and the activities of enzymes that detoxify HjOj in other cellular compartments were abnormal. 

A discussion of all the enzymes known to be associated with the nucleus is unnecessary for the purposes of this text however, it might be valuable to review the nuclear association of some hydrolytic enzymes. The presence of adenosine triphosphatase in the nucleus remains controversial. Although some investigators found it in large amounts, none was present in the nuclear preparations of others but since dinitro-phenol, which activates mitochondrial adenosine triphosphatase, has no effect on the nuclear enzyme, it seems that nuclear adenosine triphosphatase is different from the mitochondrial enzyme. The association of phosphorylase with the nucleus is also puzzling it is not clear what part the enzyme plays in the synthesis or breakdown of nuclear glycogen. 

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