Synthesis of ATP

TABLE 5.11 Agents Causing Sustained Elevation of Cytosolic Ca and/or Impaired Synthesis of ATP... 

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. 

As we have seen, the metabolic energy from oxidation of food materials—sugars, fats, and amino acids—is funneled into formation of reduced coenzymes (NADH) and reduced flavoproteins ([FADHg]). The electron transport chain reoxidizes the coenzymes, and channels the free energy obtained from these reactions into the synthesis of ATP. This reoxidation process involves the removal of both protons and electrons from the coenzymes. Electrons move from NADH and [FADHg] to molecular oxygen, Og, which is the terminal acceptor of electrons in the chain. The reoxidation of NADH,... 

In 1961, Peter Mitchell, a British biochemist, proposed that the energy stored in a proton gradient across the inner mitochondrial membrane by electron transport drives the synthesis of ATP in cells. The proposal became known as... 

Assuming that 3 H are transported per ATP synthesized in the mitochondrial matrix, the membrane potential difference is 0.18 V (negative inside), and the pH difference is 1 unit (acid outside, basic inside), calculate the largest ratio of [ATP]/[ADP] [P,] under which synthesis of ATP can occur. 

Complex V catalyzes the synthesis of ATP from ADP and Pj utilizing the energy of the proton motive force across the inner membrane (Senior, 1988,1990). 

The synthesis of ATP from ADP and phosphoric acid is nonspontaneous. Consequently, ATP synthesis must be coupied to some more spontaneous reaction. Example 14-10 describes one of these reactions. 

This potential, or protonmotive force as it is also called, in turn drives a number of energy-requiring functions which include the synthesis of ATP, the coupling of oxidative processes to phosphorylation, a metabohc sequence called oxidative phosphorylation and the transport and concentration in the cell of metabolites such as sugars and amino acids. This, in a few simple words, is the basis of the chemiosmotic theory linking metabolism to energy-requiring processes. 

A dynamic model has been proposed for the synthesis of ATP during oxidative phosphorylation in which ADP and inorganic phosphate combine directly to give a quinquecovalent intermediate. While such a model may be valuable in drawing attention to the possible participation of quinquecovalent intermediates in ATP synthesis, no mention is made of the role of oxidation in this reaction. 

Reductive dechlorination in combination with the elimination of chloride has been demonstrated in a strain of Clostridium rectum (Ohisa et al. 1982) y-hexachlorocyclohexene formed 1,2,4-trichlorobenzene and y-l,3,4,5,6-pentachlorocyclohexene formed 1,4-dichlorobenzene (Figure 7.69). It was suggested that this reductive dechlorination is coupled to the synthesis of ATP, and this possibility has been clearly demonstrated during the dehalogenation of 3-chlorobenzoate coupled to the oxidation of formate in Desulfomonile tiedjei (Mohn and Tiedje 1991). Combined reduction and elimination has also been demonstrated in methanogenic cultures that transform 1,2-dibromoethane to ethene and 1,2-dibromoethene to ethyne (Belay and Daniels 1987). 

A well-known example of active transport is the sodium-potassium pump that maintains the imbalance of Na and ions across cytoplasmic membranes. Flere, the movement of ions is coupled to the hydrolysis of ATP to ADP and phosphate by the ATPase enzyme, liberating three Na+ out of the cell and pumping in two K [21-23]. Bacteria, mitochondria, and chloroplasts have a similar ion-driven uptake mechanism, but it works in reverse. Instead of ATP hydrolysis driving ion transport, H gradients across the membranes generate the synthesis of ATP from ADP and phosphate [24-27]. 

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). 

The difference in the hydrogen ion electrochemical potential, formed in bacteria similarly as in mitochondria, can be used not only for synthesis of ATP but also for the electrogenic (connected with net charge transfer) symport of sugars and amino acids, for the electroneutral symport of some anions and for the sodium ion/hydrogen ion antiport, which, for example, maintains a low Na+ activity in the cells of the bacterium Escherichia coli. 

The search for routes to phosphorylated nucleosides or phosphorylated ribose started, as mentioned in Sect. 4.7.3, with work done by Ponnamperuma (1963). The synthesis of ATP was carried out by phosphorylation of ADP using carbamoyl phosphate in the presence of Ca2+ ions as catalyst yields of up to about 20% were obtained (Saygin and Ellmauerer, 1984). 

Thus, in one cycle, eight hydrogen atoms (H+ + e ) are transferred to hydrogen-transmitting coenzymes and later oxidized to water in the respiratory chain. This process is linked to oxidative phosphorylation, i.e., the synthesis of ATP from ADP and inorganic phosphate. 

From the plastoquinone pool, the electrons pass through the cyt b6f complex, which generates much of the electrochemical proton gradient that drives the synthesis of ATP. 

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