Oxidative phosphorylation ATP synthesis

This can be used in several ways. H+-ATPase plays a key role in oxidative phosphorylation (ATP synthesis) as it transfers protons back into the matrix space with simultaneous synthesis of ATP (with temporary enzyme phosphorylation, cf. page 451). 

Matsuno-Yagi, A., and Hatefi, Y. (1993). Studies on the mechanism of oxidative phosphorylation. ATP synthesis by submitochondrial particles inhibited at Fo by venturicidin and organotin compounds. J. Biol. Chem. 268, 6168-6173. 

High Phosphoryl Transfer Potential Compounds Can Couple Carbon Oxidation to ATP Synthesis... 

Figure 18.2. Essence of Oxidative Phosphorylation. Oxidation and ATP synthesis are coupled by transmembrane proton fluxes.

Mitochondria 39% 18-22% 1,700-2,200 Protein secretion, haem synthesis, transport and degradation functions, cellular energy generation (ATP), oxidative phosphorylation, urea synthesis, gluconeogenesis, liponeogenesis, ketogenesis, p-oxidation of fatty acids, citric acid cycle, respiratory chain, etc. 

Glycolysis and the citric acid cycle (to be discussed in Chapter 20) are coupled via phosphofructokinase, because citrate, an intermediate in the citric acid cycle, is an allosteric inhibitor of phosphofructokinase. When the citric acid cycle reaches saturation, glycolysis (which feeds the citric acid cycle under aerobic conditions) slows down. The citric acid cycle directs electrons into the electron transport chain (for the purpose of ATP synthesis in oxidative phosphorylation) and also provides precursor molecules for biosynthetic pathways. Inhibition of glycolysis by citrate ensures that glucose will not be committed to these activities if the citric acid cycle is already saturated. 

FIGURE 20.1 Pyruvate produced hi glycolysis is oxidized in the tricarboxylic acid (TCA) cycle. Electrons liberated in this oxidation flow through the electron transport chain and drive the synthesis of ATP in oxidative phosphorylation. In eukaryotic cells, this overall process occurs in mitochondria. 

Wall Piece IV (1985), a kinetic sculpture by George Rhoads. This complex meehanieal art form can be viewed as a metaphor for the molecular apparatus underlying electron transport and ATP synthesis by oxidative phosphorylation. (1985 ty George Rhoaeh)... 

Whereas ATP made in glycolysis and the TCA cycle is the result of substrate-level phosphorylation, NADH-dependent ATP synthesis is the result of oxidative phosphorylation. Electrons stored in the form of the reduced coenzymes, NADH or [FADHa], are passed through an elaborate and highly orga-... 

Because the 2 NADH formed in glycolysis are transported by the glycerol phosphate shuttle in this case, they each yield only 1.5 ATP, as already described. On the other hand, if these 2 NADH take part in the malate-aspartate shuttle, each yields 2.5 ATP, giving a total (in this case) of 32 ATP formed per glucose oxidized. Most of the ATP—26 out of 30 or 28 out of 32—is produced by oxidative phosphorylation only 4 ATP molecules result from direct synthesis during glycolysis and the TCA cycle. 

Under these conditions, what is the maximum ratio of [ATP]/[ADP] attainable by oxidative phosphorylation when [PJ = 1 mM (Assume AG° for ATP synthesis = +30.5 kj/mol.)... 

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. 

Vance, J.E., eds.), pp. 116-142, Benjamin/Cummings Publishing Co., Menlo Park, California. Senior, A.E. (1988). ATP synthesis by oxidative phosphorylation. Physiological Rev. 68, 177-230. Senior, A.E. (1990). The proton-translocating ATPase of Esherichia colt. Ann. Rev. Biophys. Chem. 19,7- 1. 

Mechanistic studies have shown that TBT and certain other forms of trialkyltin have two distinct modes of toxic action in vertebrates. On the one hand they act as inhibitors of oxidative phosphorylation in mitochondria (Aldridge and Street 1964). Inhibition is associated with repression of ATP synthesis, disturbance of ion transport across the mitochondrial membrane, and swelling of the membrane. Oxidative phosphorylation is a vital process in animals and plants, and so trialkyltin compounds act as wide-ranging biocides. Another mode of action involves the inhibition of forms of cytochrome P450, which was referred to earlier in connection with metabolism. This has been demonstrated in mammals, aquatic invertebrates and fish (Morcillo et al. 2004, Oberdorster 2002). TBTO has been shown to inhibit P450 activity in cells from various tissues of mammals, including liver, kidney, and small intestine mucosa, both in vivo and in vitro (Rosenberg and Drummond 1983, Environmental Health Criteria 116). 

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