Respiration phosphorylation

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). 

Aminophenol is a selective nephrotoxic agent and intermpts proximal tubular function (121,122). Disagreement exists concerning the nephrotoxity of the other isomers although they are not as potent as 4-aminophenol (123,124). Respiration, oxidative phosphorylation, and ATPase activity are inhibited in rat kidney mitochondria (125). The aminophenols and their derivatives are inhibitors of 5-Hpoxygenase (126) and prostaglandin synthetase... 

The modes of action for niclosamide are interference with respiration and blockade of glucose uptake. It uncouples oxidative phosphorylation in both mammalian and taenioid mitochondria (22,23), inhibiting the anaerobic incorporation of inorganic phosphate into adenosine triphosphate (ATP). Tapeworms are very sensitive to niclosamide because they depend on the anaerobic metaboHsm of carbohydrates as their major source of energy. Niclosamide has selective toxicity for the parasites as compared with the host because Httle niclosamide is absorbed from the gastrointestinal tract. Adverse effects are uncommon, except for occasional gastrointestinal upset. 

Many inhibitors of substrate oxidations, substrate transport, electron transport, and ATP synthesis are known including many well-known toxins (see Sherratt, 1981 Harold, 1986 Nicholls and Ferguson, 1992). These are not discussed here except to mention specific uncouplers of oxidative phosphorylation. Classic uncouplers such as 2,4-dinitrophenol have protonated and unprotonated forms, both of which are lipid soluble and cross the inner mitochondrial membrane discharging the proton gradient. This prevents ATP synthesis and stimulates respiration. 

Hafher, R.P., Brown, G.C.. Brand, M.D. (1990). Analysis of the control of respiration rate, phosphorylation rate, proton leak rate and proton motive force in isolated mitochondria using the top-down approach of metabolic control theory. Eur. J. Biochem. 188,313-319. 

Slater, E.C., Rosing, J., Mol, A. (1973). The phosphorylation potential generated by respiring mitochondria. Biochim. Biophys. Acta 292, 534-553. 

The rate of respiration of mitochondria can be controlled by the availability of ADP. This is because oxidation and phosphorylation are tightly coupled ie, oxidation cannot proceed via the respiratory chain without concomitant phosphorylation of ADP. Table 12-1 shows the five conditions controlling the rate of respiration in mitochondria. Most cells in the resting state are in state 4, and respiration is controlled by the availability of ADP. When work is performed, ATP is converted to ADP, allowing more respiration to occur, which in turn replenishes the store of ATP. Under certain conditions, the concentration of inorganic phosphate can also affect the rate of functioning of the respiratory chain. As respiration increases (as in exercise). 

The action of uncouplers is to dissociate oxidation in the respiratory chain from phosphorylation. These compounds are toxic in vivo, causing respiration to become uncontrolled, since the rate is no longer limited by the concentration of ADP or Pj. The uncoupler that has been used most frequently is 2,4-dinitrophenol, but other compounds act in a similar manner. The antibiotic oligomycin completely blocks oxidation and phosphorylation by acting on a step in phosphorylation (Figures 12-7 and 12-8). 

Nucleic acids are not the only biomolecules susceptible to damage by carotenoid degradation products. Degradation products of (3-carotene have been shown to induce damage to mitochondrial proteins and lipids (Siems et al., 2002), to inhibit mitochondrial respiration in isolated rat liver mitochondria, and to induce uncoupling of oxidative phosphorylation (Siems et al., 2005). Moreover, it has been demonstrated that the degradation products of (3-carotene, which include various aldehydes, are more potent inhibitors of Na-K ATPase than 4-hydroxynonenal, an aldehydic product of lipid peroxidaton (Siems et al., 2000). 

In environments lacking a suitable external electron acceptor - such as dioxygen, sulfate, or ferric iron - respiration is not possible. Here, many organic compounds may be metabolized by fermenting microorganisms. Microbes of this class may create ATP by a direct coupling mechanism, using a process known as substrate level phosphorylation, SLP with an ion translocation mechanism like that employed by respirers, as already described or by a combination of SLP and ion translocation.1... 

Answer C. The toxic agent (example, 2,4-dinitrophenol) would uncouple oxidative phosphorylation, leading to a fall in ATP levels, increased respiration, and increased substrate utilization. 

Mitochondria, which are cytoplasmic organelles involved in cellular respiration, have their own chromosome, which contains 16,569 DNA base pairs (bp) arranged in a drcalar molecule. This DNA encodes 13 proteins that are subunits of complexes in the electron transport and oxidative phosphorylation processes (see Section 1, Chapter 13). In addition, mitochondrial DNA encodes 22 transfer RNAs and two ribosomal RNAs. 

Other work has indicated that chlordane and heptachlor are energy transfer inhibitors as evidenced by marked decreases in oxidative phosphorylation of rat hepatic mitochondria following in vitro incubation of the mitochondria with the pesticides (Ogata et al. 1989). Interestingly, even though heptachlor epoxide is more toxic than either chlordane or heptachlor in tests of general toxicity, it was less effective in inhibiting mitochondrial respiration. 

The metabolic machinery responsible for the heterotrophic respiration reactions is contained in specialized organelles called mitochondria. These reactions occur in three stages (1) glycolysis, (2) the Krebs or tricarboxylic acid cycle, and (3) the process of oxidative phosphorylation also known as the electron transport chain. As illustrated in... 

Uncoupling of oxidative phosphorylation from respiration in brown adipose tissue and possibly other tissues (e.g. in muscle) (Chapter 9). 

Toxicology. 2,4-Dichlorophenol (2,4-DCP) is an uncoupler of oxidative phosphorylation toxic manifestations include central nervous system depression followed by increased respiration, hyperthermia, increased blood pressure, progressive weakness, and cyanosis. 

Regardless of the source, phenolic acids are ultimately broken down to gaseous products such as CO2 and methane. This breakdown occurs by three general methods (i) aerobic respiration, using molecular oxygen as an electron acceptor, the end product being CO2, (ii) anaerobic respiration with electron acceptors such as nitrate and (iii) anaerobic fermentation with phosphorylation reactions involving no external electron acceptor (50). 

Phenolic compounds naturally occurring in plants have induced many physiological responses that duplicate those reported for ozone and/or peroxyacetylnitrate (PAN). Chlorogenic acid is a competitive inhibitor of lAA-oxidase (35) and plant growth is adversely affected by increased concentrations of auxins (36). Concentrations of chlorogenic acid are increased in tobacco tissue exposed to ozone ( ) Phenols inhibit ATP synthesis (37), oxidative phosphorylation ( ) and SH enzyme activity (27) they increase respiration (38), reduce CO2 fixation (22), modify both membrane permeability (40) and oxidation rate of reduced NADH... 

Ozone has been shown to initiate many physiological and biochemical changes in sensitive plant species. Decreases in photosynthesis and increases and decreases in respiration have occurred in response to ozonation. The bioenergetic status of mitochondria and chloroplasts is disturbed by ozone. Decreases in oxidative- and photo- phosphorylation have been reported as have increases in adenosine triphosphate and total adenylate content of plant tissue. The variable physiological responses appear to be related to the stage of symptom development at the time of analysis and to the mode of ozone exposure, viz. in vivo and in vitro. 

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