Mitochondrial creatine kinase: a key enzyme of aerobic energy metabolism

Wyss, Markus; Smeitink, Jan A.M.; Wevers, Ron A.; Wallimann, Theo

doi:10.1016/0005-2728(92)90096-k

Cited by 333 publications

(147 citation statements)

References 399 publications

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“…The values of the constants were chosen on the basis of the literature [2][3][4][19][20][21][22][23][24][25][26]. An interpretation of some of the rate constants is the following: k_Jk+5 =Km(ATP) for E2; k_7/k+7.~Ks(ADP) for E3; k_ 11/k+ 11 = Ks(ADP)Km(CrP) and k_ 12//k+ 12 = Ks(ATP)Km(Cr) for E 4.…”

Section: The Features Of the Cytoplasmic Enzymesmentioning

confidence: 99%

“…The constant values were chosen on the basis of the literature [2,3,[12][13][14][15][16][17][18][19][20]. Relatively fast substrate binding and release (E + S ~ ES) were assumed, compared to the rate of catalysis.…”

Section: Free Energy Of Atp Hydrolysismentioning

confidence: 99%

“…The ratio Xll/X12 varied from mode 1 to mode 5 to bring the steady state Pi concentration to ---2 mM which is known for the resting muscle [3,4,6,7]. The steady state concentrations of cytoplasmic metabolites at 'rest' were obtained after several iterations, going from initial X~ ..... X18 values, and are presented in Table 2.…”

Section: 'Resting System': Steady-state Concentrations Of Metabolitesmentioning

confidence: 99%

“…In the following simulations the sensitivity of the model to the variations in the exchange rate constants was investigated. The ADP constants were taken as minimal as this metabolite is believed to be the most diffusion restricted species in the ADP-ATP and Cr-CrP shuttles [3,4]. The constants for the other metabolites were assigned equal or 10 times higher than those for ADP, keeping the ratio kin//kout = 0.01 constant.…”

Section: Variations In Diffusion Constantsmentioning

confidence: 99%

“…The abundance of CrP and cytoplasmic CK activity ensure the effective buffering of the ATP pool. The second important function of CK is energy transmission from mitochondria to the places of its utilization [1][2][3]. The spatially separated isoenzymes of CK catalyze the reaction CrP + ADP * Cr + ATP in the mitochondrial and cytoplasmic compartments.…”

Section: Introductionmentioning

confidence: 99%

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Creatine-creatine phosphate shuttle modeled as two-compartment system at different levels of creatine kinase activity

Fedosov

1994

Biochimica et Biophysica Acta (BBA) - Protein Structure and Mol

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In order to characterize ADP-ATP and creatine-creatine phosphate (Cr-CrP) shuttles a minimal mathematical model with two compartments and cyclic turnover of matter was designed. The 'mitochondrial' compartment contained 'ATP-synthase' and 'mitochondrial ereatine kinase' (mitCK). The 'cytoplasmic' compartment consisted of 'ATPase', 'cytoplasmic creatine kinase' (cytCK) and an 'ADP-binding structure'. The exchange of metabolites between these compartments was limited. Different levels of cytCK and mitCK expression as welt as different exchange rate constants between the compartments were assigned to obtain several different modes. Every steady state obtained in the presence of low ATPase activity ('resting' conditions) was then disturbed by a steep activation of ATPase ('muscle performance') and afterwards the transition to a new steady state was followed in time. The ATP-buffering capacity of the system initially acquired by cytCK expression significantly increased after additional mitCK supplement. Nevertheless, even the complete Cr-CrP shuttle failed to maintain a high [ATP]/[ADP] ratio during long term 'muscle performance' due to the rate limiting CK-transphosphorylation in the mitochondria. The facilitated diffusion of Cr and CrP was not critical, and the model worked with the same efficiency even at equal permeabilities for nucleotides and guanidines. Under 'resting conditions' the main flux of matter went through the Cr-CrP shuttle, resulting in 'pumping' of CrP. This ensured a 40 s delay in the [ATP] decrease at 'work'. The partial systems without mitCK were not as effective, and this delay was 0-10 s. However, the ADP-ATP shuttle was of more importance at the steady state achieved under ' working' conditions.

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Section: The Features Of the Cytoplasmic Enzymesmentioning

confidence: 99%

Section: Free Energy Of Atp Hydrolysismentioning

confidence: 99%

Section: 'Resting System': Steady-state Concentrations Of Metabolitesmentioning

confidence: 99%

Section: Variations In Diffusion Constantsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Creatine-creatine phosphate shuttle modeled as two-compartment system at different levels of creatine kinase activity

Fedosov

1994

Biochimica et Biophysica Acta (BBA) - Protein Structure and Mol

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Immunogold transmission electron microscopic localization of arginine kinase in arthropod mitochondria

Pineda

Ellington

1998

J. Exp. Zool.

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Crystal structure of human ubiquitous mitochondrial creatine kinase

et al. 2000

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Creatine kinase (CK), catalyzing the reversible trans-phosphorylation between ATP and creatine, plays a key role in the energy metabolism of cells with high and fluctuating energy requirements. We have solved the X-ray structure of octameric human ubiquitous mitochondrial CK (uMtCK) at 2.7 A resolution, representing the first human CK structure. The structure is very similar to the previously determined structure of sarcomeric mitochondrial CK (sMtCK). The cuboidal octamer has 422 point group symmetry with four dimers arranged along the fourfold axis and a central channel of approximately 20 A diameter, which extends through the whole octamer. Structural differences with respect to sMtCK are found in isoform-specific regions important for octamer formation and membrane binding. Octameric uMtCK is stabilized by numerous additional polar interactions between the N-termini of neighboring dimers, which extend into the central channel and form clamp-like structures, and by a pair of salt bridges in the hydrophobic interaction patch. The five C-terminal residues of uMtCK, carrying positive charges likely to be involved in phospholipid-binding, are poorly defined by electron density, indicating a more flexible region than the corresponding one in sMtCK. The structural differences between uMtCK and sMtCK are consistent with biochemical studies on octamer stability and membrane binding of the two isoforms.

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Mitochondrial creatine kinase: a key enzyme of aerobic energy metabolism

Cited by 333 publications

References 399 publications

Creatine-creatine phosphate shuttle modeled as two-compartment system at different levels of creatine kinase activity

Creatine-creatine phosphate shuttle modeled as two-compartment system at different levels of creatine kinase activity

Immunogold transmission electron microscopic localization of arginine kinase in arthropod mitochondria

Crystal structure of human ubiquitous mitochondrial creatine kinase

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