Cytochrome concentration

Cytochrome concentration AOD between 424 and 409 of the differential spectra red-ox (a) and (b) ordinate scale 100 x AOD. —, NADPH cytochrome c reductase,... 

Cytochrome concentrations are expressed as millimicromoles per milligram of protein. From Litmane [92]. 

Nitric oxide ( NO) and its derivative peroxyni-trite (ONOO ) inhibit mitochondrial respiration by distinct mechanisms. Nanomolar concentrations of NO specifically inhibit cytochrome oxidase in competition with oxygen, and this inhibition is fully reversible when NO is removed. The NO inhibition of cytochrome oxidase may be involved in the cytotoxicity of NO, and may cause increased oxygen radical production by mitochondria, with may in turn lead to the generation of peroxynitrite. Mitochondrial damage by peroxynitrite may mediate the cytotoxicity of NO, and may be involved in a variety of pathologies (for review see Brown 1999). Under turnover conditions, depending on the cytochrome concentration, either the cytochrome aj -NO or the nitrite bound enzyme is formed (Sarti et al. 2000). The predominance of one of the two inhibitory pathways depends on the occupancy of the turnover intermediates. In the dark, the respiration recovers at the rate of NO dis-... 

Brady, K., Herrera, Y. and Zenick, H. (1975). Influence of parental lead exposure on subsequent learning ability of offspring. Pharmacol. Biochem. Behav., 3, 561 Brashear, C. W., Kopp, V. J. and Krigman, M. R. (1978). Effect of lead on the developing peripheral nervous system. J. Neuropathy Exp. Neurol., 31 414 Brennan, M. J. W. and Cantrill, R. C. (1979). o-Aminolaevulinic acid is a potent agonist for GABA autoreceptors. Nature (London), 280, 514 Brown, D. R. Neonatal lead exposure in the rat decreased learning as a function of age and blood lead concentrations. Toxicol. Appl. Pharmacol., 32, 628 Bull, R. J., Lutkenhoff, S. D., McCarty, G. E. and Miller, R. G. (1979). Delays in the postnatal increase of cerebral cytochrome concentrations in lead-exposed rats. Neuropharmacol, 18, 83... 

FIGURE 2. The effect of cytochrome concentration on the apparent first order rate constant for the reaction with P700 following a flash. The results are derived from a series of experiments similar to that shown in Fig. 1. 0. Low salt medium. The points shown are the mean values for... 

Further support for the idea of complex formation was provided by measurements of the photooxidation of substrate amounts of cytochrome c in continuous light. The observed time courses were exponential rather than linear even at the highest cytochrome concentrations used. A similar result is well-established in the analogous assay with mitochondrial cytochrome oxidase and is believed to be caused by binding of both oxidised and reduced cytochrome to the oxidase with equal affinity (reviewed by Wikstrom et al, 1981). The effect of cytochrome concentration on the rate is shown in Fig. 3. In contrast to the usual observation with the mitochondrial enzyme, there is evidence for only one binding site, with a K... 

This is the reverse Pasteur or Crabtree effect and is also known as glucose inhibition or cataboHte repression. In the presence of higher sugar concentrations, synthesis of respiratory enzymes such as cytochromes is inhibited. 

Miconazole. Miconazole nitrate [22832-87-7] (Fig. 2), the 1-phenethyl-imidazole derivative first described in 1969, interferes at low doses with the cytochrome P-450 dependent ergosterol biosynthesis in yeasts and fungi. The result is accumulation of C-14 methylated sterols on the one hand and reduction of the ergosterol levels in the membranes on the other hand (12). Analogous to clotrimazole, this leads to a disturbance in the membranes it results in inhibition of ceU repHcation, mycelium development (in C. albicans) and finally, ceU death. High concentrations of miconazole, which may be achieved with topical use, disturb the orientation of phosphoHpids in the membranes, which produces leaks (13). 

Second, most membrane materials adsorb proteins. Worse, the adsorption is membrane-material specific and is dependent on concentration, pH, ionic strength, temperature, and so on. Adsorption has two consequences it changes the membrane pore size because solutes are adsorbed near and in membrane pores and it removes protein from the permeate by adsorption in addition to that removed by sieving. Porter (op. cit., p. 160) gives an illustrative table for adsorption of Cytochrome C on materials used for UF membranes, with values ranging from 1 to 25 percent. Because of the adsorption effects, membranes are characterized only when clean. Fouling has a dramatic effect on membrane retention, as is explained in its own section below. 

FIGURE 6.28 Examples of protein domains with different numbers of layers of backbone strnctnre. (a) Cytochrome c with two layers of a-helix. (b) Domain 2 of phosphoglycerate kinase, composed of a /3-sheet layer between two layers of helix, three layers overall, (c) An nnnsnal five-layer strnctnre, domain 2 of glycogen phosphorylase, a /S-sheet layer sandwiched between four layers of a-helix. (d) The concentric layers of /S-sheet (inside) and a-helix (outside) in triose phosphate isomerase. Hydrophobic residnes are bnried between these concentric layers in the same manner as in the planar layers of the other proteins. The hydrophobic layers are shaded yellow. (Jane Richarelson)... 

The poisoning effect of molecules such as CO and PF3 (p. 495) arises simply from their ability to bond reversibly to haem in the same manner as O2, but much more strongly, so that oxygen transport is prevented. The cyanide ion CN can also displace O2 from oxyhaemoglobin but its very much greater toxicity at small concentrations stems not from this but from its interference with the action of cytochrome a. 

Neurodegeneration. Figure 3 Illustration of synaptic (neuritic) apoptosis. A pyramidal neuron is depicted with cortical afferents synapsing on its dendrites. Localized apoptotic mechanisms lead to the release of cytochrome c from the mitochondria and an increase in the concentration of activated caspase-3 in a presynaptic terminal that is synapsing on a dendritic spine. Increased caspase-3 activity results in a localized breakdown of this nerve terminal and its synapse. Subsequently, the postsynaptic dendritic spine retracts and disappears (Figure modified from Glantz et al. [5] [3]). 

Imidazole antimycotics, ketoconazole, clotrimazole, and miconazole are potent inhibitors of various cytochrome P450-isoenzymes that also affect the metabolism of retinoids. They were fust shown to inhibit the metabolism of RA in F9 embryonal carcinoma cells. When tested in vitm liarazole, a potent CYP-inhibitor, suppressed neoplastic transformation and upregulated gap junctional communication in murine and human fibroblasts, which appeared to be due to the presence of retinoids in the serum component of the cell culture medium. Furthermore, liarazole magnified the cancer chemopreventive activity of RA and (3-carotene in these experiments by inhibiting RA-catabolism as demonstrated by absence of a decrease in RA-levels in the culture medium in the presence of liarazole over 48 h, whereas without liarazole 99% of RA was catabolized. In vivo, treatment with liarazole and ketoconazole reduced the accelerated catabolism of retinoids and increased the mean plasma all-irans-RA-concentration in patients with acute promyelocytic leukemia and other cancels. 

Shi J, Hui L, Xu Y, et al Sequence variations in the mu-opioid receptor gene (OPRM1) associated with human addiction to heroin. Hum Mutat 19 459 60, 2002 Shinderman M, Maxwell S, Brawand-Arney M, etal Cytochrome P4503A4 metabolic activity, methadone blood concentrations, and methadone doses. Drug Alcohol Dependence 69 205-211, 2003... 

Exposure. Known biomarkers of exposure to endosulfan include the measurement of endosulfan or its metabolites in tissue and excreta (Deema et al. 1966 Dorough et al. 1978 Gorbach et al. 1968) these measurements can indicate whether absorption of endosulfan has occurred. The presence of the parent compound and its metabolites are specific biomarkers for endosulfan exposure. However, no studies are available that quantify the concentrations of endosulfan or its metabolites in relation to specific environmental exposure levels. Since endosulfan induces cytochrome P450-dependent monooxygenases... 

Many drugs when administered to humans can result in a marked increase in ALASl. Most of these drugs are metabolized by a system in the liver that utilizes a specific hemoprotein, cytochrome P450 (see Chapter 53). During their metabolism, the utilization of heme by cytochrome P450 is greatly increased, which in turn diminishes the intracellular heme concentration. This latter event effects a derepression of ALASl with a corresponding increased rate of heme synthesis to meet the needs of the cells. 

---