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

Fedosov, Sergey N.

doi:10.1016/0167-4838(94)90109-0

Cited by 12 publications

(7 citation statements)

References 28 publications

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“…Whether or not these diVerences also aVect phosphate stimulated respiration remains to be elucidated. Also, a possible eVect of especially the mitochondrial CK activity remains to be elucidated (Fedosov 1994).…”

Section: Discussionmentioning

confidence: 99%

Regulation of mitochondrial respiration by inorganic phosphate; comparing permeabilized muscle fibers and isolated mitochondria prepared from type-1 and type-2 rat skeletal muscle

Scheibye‐Knudsen

Quistorff

2008

Eur J Appl Physiol

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ADP is generally accepted as a key regulator of oxygen consumption both in isolated mitochondria and in permeabilized fibers from skeletal muscle. The present study explored inorganic phosphate in a similar regulatory role. Saponin permeabilized fibers and isolated mitochondria from type-I and type-II muscle from male Wistar rats were prepared. Respiration was measured while the medium P(i) concentration was gradually increased. The apparent K(m) values for P(i) were 607 +/- 17 microM and 405 +/- 15 microM (P < 0.0001) for type-I and type-II fibers, respectively. For isolated mitochondria the values were significantly lower than type-1 permeabilized fibers, 338 +/- 130 microM and 235 +/- 30 microM (P < 0.05), but not different with respect to fiber type. The reason for this difference in K(m) values in the permeabilized muscle is unknown, but a similar pattern has been observed for K(m) of ADP. Our data indicate that phosphate may play a role in regulation of oxygen consumption in vitro and in vivo.

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Section: Discussionmentioning

confidence: 99%

Regulation of mitochondrial respiration by inorganic phosphate; comparing permeabilized muscle fibers and isolated mitochondria prepared from type-1 and type-2 rat skeletal muscle

Scheibye‐Knudsen

Quistorff

2008

Eur J Appl Physiol

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“…Computation and Statistics. The data fitting was performed by the computer program for regression analysis and simulation of metabolic chain reactions (Fedosov, 1995). The statistical data are presented as mean ±SD.…”

Section: Methodsmentioning

confidence: 99%

Binding of cobalamin and cobinamide to transcobalamin from bovine milk

Fedosov

Petersen²,

Nexø³

1995

Biochemistry

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We have studied the interaction between transcobalamin (TC) and the ligands cobalamin (Cbl) and cobinamide (Cbi). Partially purified TC from bovine milk was depleted of endogenous Cbl by 8 M urea treatment. Unsaturated TC was adsorbed on CM-Sepharose in order to ensure fast separation of the matrix-bound protein from the reaction medium. The forward reaction TC+Cbl-->TC-Cbl (rate constant k+Cbl) and the backward reaction TC-Cbl-->TC+Cbl (k-Cbl) were followed in time. A single-step binding model (with no intermediate protein-ligand complex) was sufficient to fit the data. The calculated rate constants were k+Cbl = 0.6 nM-1 min-1 and k-Cbl = 1.3 x 10(-4) min-1, which corresponded to the TC-Cbl dissociation constant KDCbl = 0.2 pM. Reaction between TC and Cbl developed against electrostatic forces, and the effective charges of the interacting species were estimated as both +1 or both -1. The competition between Cbl and Cbi for TC was studied, which resulted in determination of the relevant rate constants for Cbi: k+Cbi = 0.03 nM-1 min-1, k-Cbi = 0.03 min-1, and KDCbi = 1 nM. Slow dissociation of TC-Cbl guarantees its stability in plasma for 5-10 h, while Cbi bound to TC would be transferred to haptocorrin in less than 1 h.

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“…These analyses neglect changes in [ATP] which are not seen in the present experiments, but can be incorporated into both linear [66] and ADP-control models [73]. Lastly, attempts have been made to avoid assuming that creatine kinase is necessarily at equilibrium, and to allow for possible roles of mitochondrial creatine kinase [4,74,75].…”

Section: Mitochondrial Regulationmentioning

confidence: 99%

Muscle oxygenation and ATP turnover when blood flow is impaired by vascular disease

Kemp

Roberts

Bimson

et al. 2002

Journal of Spectroscopy

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In exercising muscle, creatine kinase ensures that mismatch between ATP supply and ATP use results in net phosphocreatine (PCr) splitting. This,inter alia, makes31P magnetic resonance spectroscopy a useful tool for studying muscle ‘energy metabolism’ noninvasivelyin vivo. We combined this with near–infrared spectroscopy (NIRS) to study ATP synthesis and oxygenation in calf muscle of normal subjects and patients with peripheral vascular disease. Experimental and clinical details and basic data have been published elsewhere (G.J. Kemp et al.,Journal of Vascular Surgery34 (2001), 1103–10); we here propose an analysis of interactions between metabolic ‘error signals’ and cellular PO2(estimated from NIRS changes, provisionally assumed to reflect deoxymyoglobin). Post–exercise PCr recovery is monoexponential, and the linear relationship between PCr resynthesis rate (= oxidative ATP synthesis) and the perturbation in PCr (conceptually the simplest error signal) is consistent with negative feedback. In patients the inferred ‘mitochondrial capacity’ (= oxidative ATP synthesis at ‘zero’ PCr) is decreased by 53±6%, leading to reduced oxidative ATP contribution in exercise, because of increased deoxygenation. Increased PCr perturbation partially outweighs cellular hypoxia, but as low cellular PO2is required for capillary–mitochondrion O2diffusion, rate–signal relationships may overstate maximum oxidative ATP synthesis rate.

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

Cited by 12 publications

References 28 publications

Regulation of mitochondrial respiration by inorganic phosphate; comparing permeabilized muscle fibers and isolated mitochondria prepared from type-1 and type-2 rat skeletal muscle

Regulation of mitochondrial respiration by inorganic phosphate; comparing permeabilized muscle fibers and isolated mitochondria prepared from type-1 and type-2 rat skeletal muscle

Binding of cobalamin and cobinamide to transcobalamin from bovine milk

Muscle oxygenation and ATP turnover when blood flow is impaired by vascular disease

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