Inhibition/inhibitors respiration

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). 

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. 

ATP is synthesized. Addition of cyanide (CN ), which blocks electron transfer between cytochrome oxidase and 02, inhibits both respiration and ATP synthesis, (b) Mitochondria provided with succinate respire and synthesize ATP only when ADP and P, are added. Subsequent addition of venturicidin or oligomycin, inhibitors of ATP synthase, blocks both ATP synthesis and respiration. Dinitrophenol (DNP) is an uncoupler, allowing respiration to continue without ATP synthesis. 

Recently Kerkenaar and Kaars Sijpesteijn (1979) demonstrated that inhibition of respiration cannot be the primary cause of growth inhibition, and that the action of tridemorph is similar to that of known sterol biosynthesis inhibitors. Their study seems to favour in lipid biosynthesis, possibly ergosterol biosynthesis, as a primary mode of action of tridemorph, and would agree with the rather late interference of this compound with protein and RNA synthesis (Kerkenaar et al., 1979, 1981). 

MPP+ is a potent inhibitor of oxidation of the NAD+-linked substrates pyruvate/malate and glu-tamate/malate in isolated rat liver and brain mitochondria, while leaving the oxidation of succinate unaffected (Nicklas et al., 1985). The locus of inhibition of the mitochondrial respiration is assumed to be between the highest potential Fe-S cluster in NADH dehydrogenase and the coenzyme Q located probably at the rotenone-binding site (Ramsay et al., 1991). As a consequence of inhibition of respiration, cellular energy supplies in the form of ATP would rapidly be consumed, followed by depolarization of membranes, probable Ca influx and overstimulation of Ca +-dependent lysosomal enzymes. 

Sorgoleone was initially found to inhibit mitochondrial respiration, but it was later found to be a more potent inhibitor of photosyndietic electron transport of photosystem II (PSII) IS, 16). Sorgoleone is structurally similar to plastoquinone (PQ), a benzoquinone involved in photosyndietic electron transport. Sorgoleone competes for the PQ binding site of die D-1 protein in a manner similar to most commercial photosynthetic inhibitors IT). The in vitro PSII inhibiting activity of sorgoleone is similar to some of the commercial herbicides targeting this site e.g., atrazine and diuron). 

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... 

Barbiturates such as amobarbital inhibit NAD-hnked dehydrogenases by blocking the transfer from FeS to Q. At sufficient dosage, they are fatal in vivo. Antin cin A and dimercaprol inhibit the respiratory chain between cytochrome b and cytochrome c. The classic poisons H2S, carbon monoxide, and cyanide inhibit cytochrome oxidase and can therefore totally arrest respiration. Malonate is a competitive inhibitor of succinate dehydrogenase. 

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