Adenosine 5 -triphosphate mitochondrial synthesis

An ex vivo study with rat hepatocytes found a strong correlation between the cytotoxicity of a flavonoid and its ability to induce an early collapse of the mitochondrial transmembrane potential [6]. In contrast, nontoxic flavonoids had no effect on the transmembrane potential. As discussed previously, the ability of flavonoids and isoflavones to inhibit mitochondrial respiration and adenosine triphosphate (ATP) synthesis or uncouple oxidative phosphorylation represents a potential mechanism whereby they can trigger dissipation of the transmembrane potential and thus cytochrome c-dependent apoptosis. Thus, it is interesting to note that epicatechin, which had little or no proapoptotic effect in cancer cells [64] and exerted antiapoptotic effects in primary culture models [7,8,59], had essentially no inhibitory effect against complex I, II, or HI activity and FoFi-ATPase activity [24,25]. However, the preceding discussion has also indicated that the pro- or antiapoptotic effects of flavonoids may be explained by more specific mechanisms, potentially independently of their antioxidant capacity. These include effects on protein kinase cascades and gene expression, including MARK and the Bcl-2 family of proteins. 

Mechanism of Action A systemic anti-infective that inhibits the mitochondrial electron-transport system at the cytochrome bcl complex (Complex 111), which interrupts nucleic acid and adenosine triphosphate synthesis. Therapeutic Effect Antiprotozoal and antipneumocystic activity. 

Oxidative phosphorylation The process by which adenosine triphosphate (ATP) is synthesized from a hydrogen ion gradient across the mitochondrial inner membrane. The hydrogen ion gradient is formed by the action of protein complexes in the mitochondrial membrane that sequentially transfer electrons from the rednced cofactors nicotinamide adenine dinucleotide (NADH) and FADH to molecnlar oxygen. Movement of hydrogen ions back into the mitochondrion via ATP synthase drives the synthesis of ATP. 

Atovaquone is an antiprolozoal agent (750 mg p.o. t.i.d for 21 days), that inhibits mitochondrial electron transport in metabohc enzymes of microorganisms. This may cause inhibition of nucleic acid and adenosine triphosphate synthesis. Atovaquone is indicated in the treatment of mild to moderate Pneumocystis carinii pneumonia in patients who cannot tolerate trimethoprimsulfamethoxazole, and in acute oral treatment of mild to moderate PCP in patients who are intolerant to trimethoprimsulfamethoxazole. 

Mitchell/ Peter Dennis (1920-92) English biochemist who revolutionized thought on the process of oxidative phosphorylation in which adenosine triphosphate (ATP) is regenerated from adenosine diphosphate (ADP) and phosphate. Breakdown of ATP to ADP releases large amounts of energy for cell functions from the phosphate bonds. MitcheU proposed that electron transport formed a proton gradient across the mitochondrial membrane that directly brought about the synthesis of ATP from ADP. He was awarded the 1978 Nobel Prize in chemistry. 

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