ATP synthase activation

Snyder JW, Pastorino JG, Thomas AP, et al. 1993. ATP synthase activity is required for fructose to protect cultured hepatocytes from the toxicity of cyanide. Am J Physiol Cell Physiol 264(3) C709-C714. 

S ATP -I- 1 D-myo-inositol hexakisphosphate <1> (<1>, enzyme is responsible for the biosynthesis of diphospho-myo-inositol pentakisphosphate. The enzyme also has a ATP synthase activity, implying that 5-diphos-pho-1 D-myo-inositol pentakisphosphate functions as high-energy phosphate donor [1]) (Reversibility r <1> [1]) [1]... 

FIGURE 19-58 Comparison of the topology of proton movement and ATP synthase orientation in the membranes of mitochondria, chloroplasts, and the bacterium E. coli. In each case, orientation of the proton gradient relative to ATP synthase activity is the same. 

ATP synthase activity can be restored by adding back the F] complex to the depleted membranes. The F[ complexes bind to membrane channels known as the F complex, which are also composed of multiple subunits. The polypeptides of the F0 component are very hydrophobic and form a proton transport channel through the membrane, which links the proton gradient to ATP synthesis. This channel appears to be lined with hydrophilic residues such as seryl, threonyl and carboxyl groups. The stalk that connects the F, to the F complex comprises one copy each of the polypeptide known as the oligomycin-sensitivity-conferring protein (OSCP) and another protein known as F6. 

The A/iNa formed may be converted via a Na /H antiporter into a AftfT which then drives the synthesis of ATP via a DCCD-sensitive H -translocating ATP synthase. This ATP formation explains net ATP synthesis coupled to acetate formation from H2/CO2 [192,195,199], Alternatively, A/lNa" could drive ATP synthesis directly via Na "-translocating ATP synthase. A Na -stimulated ATP-synthase activity has recently been reported for Acetobacterium woodii [200]. 

The chloroplast thylakoids were first incubated in apH=5 medium and then rapidly changed to a basic medium with pH fixed at 8.2. The acid incubation period was restricted to 30 sec to minimize inactivation of the ATP synthase activity. AT values were maintained at 5,44 or 60 mV. At ApH=3.2 and each given AT, a linear increase in the ATP yield was observed up to a reaction time of 200 ms. The authors thus concluded that within this time span both ApH and AT remained practically constant. The slopes of the three curves, representing the rates of ATP synthesis at ApH=3.2, are 120,260 and 380 mmol ATP/mol Chi for AT equal to 5,44 and 60 mV, respectively. The rate of ATP synthesis gradually decreased after the initial linear portion and eventually approached zero, as ApH and AT decayed to approach threshold values completely. The three separate plots clearly show that the eventual ATP yield as well as the initial ATP rate increases with increasing amplitude of the diffusion potential AT. 

ATP synthase activity upon reduction of the disulfide bond with DTT. It is also possible to exchange the two originally non-crosslinked p-subunits withradiolabeledsubunits. 

Fig. 40. Two similar models for ATP synthase. (A) The Capaldi model shows cross-links between various Fq and F, subunits which result in blocking or not blocking enzymatic activity the open bow-ties are used to represent cross-links that do not affect the ATP synthase activity and the black bow-ties those that do. (B) The Junge model places emphasis on the structural sectors of the "motor" and the engine parts, the rotor and stator. See text for discussion. (A) Adapted from Ogilvie, Aggeler and Capaldi (1997) Cross-linking of the subunit to one of the three a subunits has no effect on functioning as expected if is a part of the stator that links the Fi and Fo ports of the Escherichia coliA TP synthase. J Biol Chem 272 16655 (B) Adapted from Junge, Lill and Engelbrecht (1997) A TP synthase an electrochemical transducer with rotatory mechanics. Trends in Biochem Sci 22 420. Also cf. model of Peter GrSber in color in Color Plate 17.

Obeying the laws of thermodynamics. Why will isolated F] subunits display Al Pase activity and not ATP synthase activity ... 

Protons, which are present in the intermembrane space in great excess, can pass through the inner membrane and back into the matrix down their concentration gradient only through special channels. (The inner membrane itself is impermeable to ions such as protons.) As the thermodynamically favorable flow of protons occurs through a channel, each of which contains an ATP synthase activity, ATP synthesis occurs. 

FqFi complex The enzyme complex in the inner mitochondrial membrane that uses energy from the transmembrane proton gradient to catalyze ATP synthesis. The Fq portion of the complex spans the membrane, and the Fi portion, which performs the ATP synthase activity, projects into the mitochondrial matrix. 

It should be taken into account that the state 3 respiration rate is eontroUed by (1) the aetivity of the reactions involved in the oxidation of the substrates and in the produetion of membrane potential, including the activities of electron transport chain complexes and (2) the activity of reactions that use the membrane potential for the synthesis and the export of ATP, ineluding ATP synthase activity. The absence of an age-related change in state 3 respiration, despite a reduction of the aetivity of each individual complex of the electron transport chain as well as of the ATP synthase eomplex, support the hypothesis that supramolecular assembly of respiratory ehain eomplexes into respirasomes (described in the previous chapter) can compensate for the eomplex being present at the lower levels and activities in old mitochondria. 

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