Respiratory control ratio

Polarographic studies of a mitochondrial fraction from Hymenolepis diminuta showed that of four substrates tested, DL-glycerol-3-phosphate was the most rapidly oxidized, but the highest respiratory control ratio (1.7) was obtained with dl-isocitric acid. With isocitrate as substrate oxyclozanide at 1.61 nM stimulated O uptake and relieved oligomycin inhibition of adinosine diphosphate-stimulated respiration, but at concentrations above 2 pM progressively inhibited O uptake. Rafoxanide, niclosamide, 3,4,5-tribromo-salicylanilide, nitroxynil, resorantel, di-chlorophen, and 2,4-dinitrophenol exhibited effects similar to those of oxyclozanide on the respiration in cestode mitochondria. The relative potencies were compared and the possible mode of action discussed [38]. 

Gpxl-deficient mice Increase in ROS level and in lipid peroxidation level in liver decrease in liver mitochondrial respiratory control ratio and power output index Growth retardation E3... 

Note The respiratory control ratio was calculated as the ratio of oxygen uptake following, and prior to, the addition of ADP. 02 uptake was measured polarographically. 

JNK activation may be a mechanism that is associated with the initiation of mitochondrial permeability transition (MPT) (Hanawa et al. 2008 Latchoumycan-dane et al. 2006, 2007). As discussed above, both JNK activation (Matsumaru et al. 2003) and MPT (Lemasters 1998) are known to occur as a result of increased oxidative stress. MPT leads to additional oxidative stress with loss of mitochondrial membrane potential and loss of the ability of the hepatocyte to synthesize ATP. Latchoumycandane et al. (2006, 2007) found that leflunomide protected mice from mitochondrial permeabilization. Direct evidence for a role of JNK activation in acetaminophen-induced MPT was recently reported by Hanawa et al. (2008). A time course of events indicated GSH depletion by 1-2 h, JNK activation in liver homogenate by 2-4- h, JNK translocation to mitochondria by 4 h, and increased toxicity (serum ALT by 6 h). The JNK inhibitor did not alter GSH depletion but blocked JNK activation in homogenate, JNK translocation to mitochondria, and toxicity. Mitochondria from liver of acetaminophen-treated mice showed decreased State III respiration and decreased respiratory control ratios, whereas mice treated with acetaminophen plus JNK inhibitor were partially protected from these losses. Addition of activated JNKl or JNK2 to mitochondria from acetaminophen-treated mice plus JNK inhibitor showed a decrease in State 111 respiration and decreased respiratory control ratio. Addition of the MPT inhibitor cyclosporine A prevented these decreases. It was hypothesized that activated JNK is an important mediator of acetaminophen-induced MPT (Hanawa et al. 2008). 

No effects in isolated mitochondrial preparations on state 4 respiration, ADP-stimulated or 2,4-dinitrophenol-stimulated respiration, the respiratory control ratio, the adenosine diphosphate/oxygen ratio, the rate of calcium-induced mitochondrial swelling at 50 pM. Loss of MMP was seen rally at the highest concentration of ximelagatrtm tested, 300 pM, in mitochondria exposed for 24 h. No effects on P-oxidation of fatty acids up to 300 pM... 

Respiratory control ratio 28 days Decreased Holtzman and Hsu, 1976... 

Fig. 5.7A-C. Changes in (A) respiratory control ratio RCR) (B) ADP/0 ratio and (C) mitochondrial cytochrome oxidase activity in intact cotyledons of dark-grown Alaska peas. Based on Nawa et al., 1973 [96]...

A different and simpler approach to the measurement of P/O ratios came from the introduction of an oxygen electrode suitable for biochemical studies. Chance and Williams (1955) established conditions under which mitochondrial respiration, in the presence of excess substrate, was totally dependent on the amount of ADP available, i.e., the mitochondria were exhibiting respiratory control. From the change in potential when a known amount of ADP was admitted into the electrode vessel, the oxygen uptake and thus the P/O ratio could be determined, completely confirming the earlier results. 

Optimum living conditions also give rise to intensification of aerobic metabolism. Within the zone of temperature tolerance, the intensification depends directly upon temperature (Van t Hoff-Arrhenius law). Many workers have shown that, in the optimum temperature zone, there are increases in oxygen consumption, activities of cytochrome oxidase and succinic dehyrogenase, respiration/phosphorylation ratio (respiratory control) and muscle electrical potential (Hochachka and Somero, 1973,1977 Wodtke, 1974 Khaskin, 1975 Derkatchev et al., 1976 Walesby and Johnston, 1980 Romanenko etal., 1991). 

ADP phosphorylation is tightly coupled to electron transport. Shutting down one shuts down the other. It is well known that if ADP phosphorylation is inhibited by such compounds as oligomycin, electron transport also ceases. If the proton gradient is broken by a proton ionophore, however, such as 2,4-dinitrophenol, electron transport resumes at a rapid pace and no phosphorylation takes place. Such proton ionophores are also termed "uncouplers" of electron transport and ADP phosphorylation. Under normal conditions, the factors limiting ATP production are the pH gradient across the inner mitochondrial membrane and the cellular ADP/ATP ratio. An increase in the proton gradient shuts down phosphorylation and electron transport, whereas an increase in the ADP/ATP ratio stimulates both. Stimulation of oxidative phosphorylation by increases in cellular ADP concentration is termed respiratory control. 

Respiratory Control Ion Accumulated (nmol/mq protein) Ratio... 

The values of P/O change within the range of 1-3, and characteristic of the substrate undergoing oxidation and characteristic of the organ s physiological role. In the case of excess oxygen and inorganic phosphate, the respiratory activity of the mitochondria is controlled by the amount of ADP available. In the controlled state called state 4, the amount of ADP is low. With the addition of ADP, the respiratory rate increases sharply this active state is called state 3. The ratio of the respiratory rates of state 3 to state 4 is called the respiratory control index. 

The mung bean mitochondria had respiratory control (state 3/state 4) ratios that averaged 3.9, 3.6, and 2.2 and calculated ADP/0 ratios that averaged 2.3, 1.3, and 1.5, for the oxidation of malate, NADH, and succinate, respectively. 

Data are based on cytox activity. To obtain some information on the total capacity per cell, data were converted to Ot consumption per total cell DNA. Respiration and cytox were measured polarograpbically. Respiratory control was between 2 and 4 for embryo-mitochondrial fractions. ADP/0 ratios succinate ca. 1.9 -hydroxybutyrate ea. 2.6 [Pg.437]

As the cotyledonary reserves are consumed the mitochondria become disorganized and gradually lose their respiratory efficiency, enzyme complement and activity. In cotyledons of dark-grown Alaska peas this is marked by a decline in respiratory control (Fig. 5.7A), a loss of efficiency of oxidative phosphorylation (shown by the fall in ADP/0 ratio) (Fig. 5.7 B) and in cytochrome oxidase activity (Fig. 5.7 C). Another mitochondrial enzyme, malate dehydrogenase does not decline however. The gradual loss of mitochondrial activity is accompanied by the disruption of cell structure (see Chap. 6). 

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