Inhibition of the soluble adenosine triphosphatase from mitochondria by adenylyl imidodiphosphate

Philo, R D; Selwyn, Michael J.

doi:10.1042/bj1430745

Cited by 37 publications

(10 citation statements)

References 5 publications

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“…1, the inhibition is substantial (compare with trace a) but not as great as the maximal inhibition produced when zinc is present initially (trace c). Trace d also shows that inhibition by zinc is time dependent but fairly rapid on the time scale of these experiments with a f,, of about 2 s (estimated by fitting a first-order exponential expression to the development of inhibition [22] by non-linear regression). This time dependence may lead to an underestimation of inhibition, particularly at low zinc concentrations.…”

Section: Resultsmentioning

confidence: 80%

The pH‐dependent anion‐conducting channel of the mitochondrial inner membrane is potently inhibited by zinc ions

Selwyn

Choo

1993

FEBS Letters

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Zinc is a potent reversible inlubitor of the pH-dependent anion-conductmg channel m the mitochondrial inner membrane, 50% inhibition was produced by 1.5 PM added Zn" at which point free Zn" was 5 10~8 M. Inhibition by Zn" IS rapid but can be prevented or rapidly reversed by excess EDTA. Concentrations of Zn" higher than 4 PM caused reversal of inhibition to a variable extent depending on the anion. Under these conditions Zn*' did not inhibit ribose entry, the phosphate transporter, or the pH-Insensitive component of the NO,-uniport.

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Section: Resultsmentioning

confidence: 80%

The pH‐dependent anion‐conducting channel of the mitochondrial inner membrane is potently inhibited by zinc ions

Selwyn

Choo

1993

FEBS Letters

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“…2). Philo & Selwyn (1974) and Schuster et al (1975Schuster et al ( , 1976 believe that the hydrolysis of ATP and GTP occurs in the different nucleotide-binding sites of factor F1. However, the results obtained by us (the inhibition of the ATPase and GTPase activities of factor F1 as the result of binding by the enzyme of one nucleotide residue) are in better agreement with the suggestion that the hydrolysis of ATP and GTP occurs in one and the same site of factor F1.…”

Section: Resultsmentioning

confidence: 99%

Mixed anhydrides of nucleotides and mesitylenecarboxylic acid as new specific inhibitors of mitochondrial adenosien triphosphatase

Kozlov¹,

Shalamberidze²,

Novikova³

et al. 1979

Biochemical Journal

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Mixed anhydrides of nucleoside triphosphates and mesitylenecarboxylic acid inhibit soluble mitochondrial ATPase (adenosine triphosphatase), but do not inhibit ATPase of submitochondrial particles. Inhibition of soluble mitochondrial ATPase by the mixed anhydride of epsilon-ATP and mesitylenecarboxylic acid is followed by the covalent binding of one nucleotide residue to a molecule of the protein. It is suggested that this covalent binding occurs in the catalytic site of the mitochondrial ATPase. The mixed anhydride of ADP and mesitylenecarboxylic acid inhibits the ATPase activity of submitochondrial particles and has no effect on the activity of soluble mitochondrial ATPase. After separation of the submitochondrial particles from the mixed anhydride of ADP and mesitylenecarboxylic acid, their ATPase activity is restored to its original value (half-time of reactivation 3--4 min). Incubation of submitochondrial particles or soluble mitochondrial ATPase with the mixed anhydride of ADP and mesitylenecarboxylic acid results in AMP formation.

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“…At pH 7.8, k+4 is 6.7 x 10-2 S-1, k4 is 3.8 x 10-3S-1 and K q is 17.6. Therefore k+4 is higher than k 4, indicating that EI* will be favoured over EI and thus explaining the stability of the inhibition of the ATPase (Philo & Selwyn, 1974;Harris et al, 1978).…”

Section: Kinetic Parametermentioning

confidence: 99%

“…[fly-Imido]ATP has also been shown to be a potent competitive inhibitor of F1-ATPase activity (Schuster et al, 1975a), of the ATP-dependent reduction of NAD+ by succinate and of ATP-[32P]P1 exchange; however, it does not affect the ATP synthesis from ADP and Pi (Penefsky, 1974). [f7-Imido]ATP inhibits F1-0306-3283/83/030727-09$2.00 (© 1983 The Biochemical Society ATPase in a time-dependent manner, forming a relatively stable complex (Philo & Selwyn, 1974;Harris et al, 1978), and Harris et al (1981) have shown that it inhibits by binding to the hydrolytic site of the enzyme. The stoicheiometry of the binding has been studied, and the presence of three exchangeable binding sites that are distinct from non-catalytic sites, i.e.…”

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A kinetic study of the interaction between mitochondrial F1 adenosine triphosphatase and adenylyl imidodiphosphate and guanylyl imidodiphosphate

Belda¹,

Carmona²,

Cánovas³

et al. 1983

Biochemical Journal

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1. The presence of 5'-adenylyl imidodiphosphate, a non-hydrolysable analogue of ATP, in the solution used to assay the soluble bovine heart mitochondrial F1-ATPase produced slow competitive inhibition. If the enzyme was preincubated with the inhibitor before the substrate, MgATP, was added, a partial re-activation was obtained. 2. The slow inhibitory process showed first-order rate kinetics, and therefore it seems likely that a conformational change of the enzyme occurs following a faster binding process. A reaction scheme is suggested. At pH 7.8 the rate constant for the inhibition reaction was calculated to be 6.7 X 10(-2)s-1 and that for the re-activation 3.8 X 10(-3)s-1, with Keq. 17.6, indicating that the inhibited enzyme-inhibitor complex will be favoured over the non-inhibited enzyme-inhibitor complex. 3. The presence of 5'-guanylyl imidodiphosphate in the solution used to assay F1-ATPase produced rapid competitive inhibition, which was then slowly reversed until a steady state was reached. This might be explained by a rapid but reversible shift of the inhibition pathway induced by this non-hydrolysable analogue of ATP. A complex rate constant for the displacement of the inhibitor by the substrate of 7.6 X 10(-3)s-1 was calculated. 4. The results are discussed in the light of other recent observations about binding of 5'-adenylyl imidodiphosphate to F1-ATPase and with reference to the binding-site-change mechanism of hydrolysis of ATP by F1-ATPase.

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Inhibition of the soluble adenosine triphosphatase from mitochondria by adenylyl imidodiphosphate

Cited by 37 publications

References 5 publications

The pH‐dependent anion‐conducting channel of the mitochondrial inner membrane is potently inhibited by zinc ions

The pH‐dependent anion‐conducting channel of the mitochondrial inner membrane is potently inhibited by zinc ions

Mixed anhydrides of nucleotides and mesitylenecarboxylic acid as new specific inhibitors of mitochondrial adenosien triphosphatase

A kinetic study of the interaction between mitochondrial F1 adenosine triphosphatase and adenylyl imidodiphosphate and guanylyl imidodiphosphate

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