Factors determining the relative contribution of the adenine-nucleotide translocator and the ADP-regenerating system to the control of oxidative phosphorylation in isolated rat-liver mitochondria
Open accessAbstract
The control exerted by the adenine nucleotide translocator and the ADP‐regenerating system on oxidative phosphorylation was studied in isolated rat‐liver mitochondria respiring with succinate. At intermediate rates of respiration the flux control coefficient (control strength) of the adenine nucleotide translocator on respiration was much higher with creatine/creatine kinase than with glucose/hexokinase as the ADP‐regenerating system. In contrast, at the same rate of respiration the flux control coefficient of creatine kinase was much lower than that of hexokinase. On addition of a small amount of carboxyatractyloside to mitochondria respiring in the presence of glucose/hexokinase or creatine/creatine kinase, the rate of respiration decreased abruptly and then increased again to a new steady state which was lower with creatine/creatine kinase than with glucose/hexokinase. In the new steady state, the extramitochondrial ATP/ADP ratio was lower with glucose/hexokinase than with creatine/creatine kinase. At the same rate of respiration, the elasticity coefficient of creatine kinase towards the extramitochondrial ATP/ADP ratio was much higher than that of hexokinase. The connectivity theorem [Kacser, H. and Burns, J. A. (1973) in Rate Control of Biological Processes (Davies, D. D., ed.) pp. 65–104, Cambridge University Press, London] which relates the flux control coefficients of two adjacent enzymes to their elasticity coefficients towards the common intermediate, provides an explanation for the difference in flux control coefficient of the adenine nucleotide translocator with the two ADP‐regenerating systems. Using principles developed by R. Heinrich and T. A. Rapoport [BioSystems 7, 130–136 (1975)], the flux control coefficients of the adenine nucleotide translocator and hexokinase on phosphorylation were also calculated from the elasticity coefficients of these enzymes towards the extramitochondrial ATP/ADP ratio and the controls exerted by these enzymes on the extramitochondrial ATP/ADP ratio. The calculated values were approximately 30% lower than the values measured directly. The elasticity coefficient of the adenine nucleotide translocator towards the extramitochondrial ATP/ADP ratio was determined, using either the connectivity theorem of Kacser and Burns (loe. cit.) or a new connectivity theorem developed by Westerhoff (following paper in this journal). Good agreement was obtained using the different methods of calculation. It is concluded that flux through the adenine nucleotide translocator, although in principle dependent on ([ATP]/[ADP])out, ([ATP]/[ADP])in and ΔΨ, is regulated primarily by ([ATP]/[ADP])out under the conditions used in this study.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Control experiments with atractyloside ensured that ADP/ATP exchange was mediated by the ADP/ATP carrier.
“Control experiments were carried out in the presence of atractyloside (ATR), a substrate of ANT, to ensure that the ADP/ATP exchange was mediated by the ADP/ATP carrier (Atlante et al., 2003; Rossignol et al., 2000; Wanders et al., 1984).”
From Mitochondrial Dysfunction Induced by Sertraline, an Antidepressant Agent (2012) · cites this paper as Wanders et al., 1984
The flux-control section reports that carboxyatractyloside inhibits flux through the adenine-nucleotide translocator, supporting the rationale for an inhibitor-based carrier control. But this paper used carboxyatractyloside rather than the citing sentence’s atractyloside control, and it describes the compound as an inhibitor, not a substrate. It cannot verify the citing authors’ own control experiments. (LLM, conf=0.87)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Heinrich, R., & Rapoport, T. A. (1974) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1974.tb03318.x · Cited by 1,400 · see citing works
WILLIAMSON, J. R., & Corkey, B. E. (1969) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(69)13072-4 · Cited by 876 · see citing works
[3] Fractionation of cell components of animal tissues
Hogeboom, G. H. (1955) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(55)01007-0 · Cited by 734 · see citing works
Respiratory granules of heart muscle
Cleland, K. W., & Slater, E. C. (1953) · Biochemical Journal · doi:10.1042/bj0530547 · Cited by 663 · see citing works
Quantification of the contribution of various steps to the control of mitochondrial respiration.
Groen, A. K., Wanders, R. J. A., Westerhoff, H. V., van der Meer, R., & Tager, J. M. (1982) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)81026-8 · Cited by 629 · see citing works
Self-citationMyers, D. K., & Slater, E. C. (1957) · Biochemical Journal · doi:10.1042/bj0670558 · Cited by 546 · see citing works
Metabolic regulation and mathematical models
Heinrich, R., Rapoport, S. M., & Rapoport, T. A. (1978) · Progress in Biophysics and Molecular Biology · doi:10.1016/0079-6107(78)90017-2 · Cited by 499 · see citing works
Molecular Democracy: Who Shares the Controls?
KACSER, H., & Burns, J. (1979) · Biochemical Society Transactions · doi:10.1042/bst0071149 · Cited by 456 · see citing works
Function and molecular aspects of biomembrane transport
Kenny, J. M. (1981) · Biochemical Education · doi:10.1016/0307-4412(81)90071-6 · Cited by 333 · see citing works
Fructose-1, 6-diphosphate Aldolase UV Assay, Manuel Method
Bergmeyer, H. U., & Bernt, E. (1974) · Elsevier eBooks · doi:10.1016/b978-0-12-091302-2.50109-2 · Cited by 251 · see citing works
(1983) · Analytical Biochemistry · doi:10.1016/0003-2697(83)90635-8 · Cited by 197 · see citing works
How do enzyme activities control metabolite concentrations?
Westerhoff, H. V., & Chen, Y.-D. (1984) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1984.tb08304.x · Cited by 153 · see citing works
The phosphorus/oxygen ratio of mitochondrial oxidative phosphorylation
Hinkle, P. C., & Yu, M. L. (1979) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)30244-2 · Cited by 150 · see citing works
Mathematical analysis of multienzyme systems. II. Steady state and transient control
Heinrich, R., & Rapoport, T. A. (1975) · Biosystems · doi:10.1016/0303-2647(75)90050-7 · Cited by 148 · see citing works
Lemasters, J. J., & Sowers, A. E. (1979) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)34194-7 · Cited by 105 · see citing works
Nicholls, D. G., & BERNSON, V. S. M. (1977) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1977.tb11560.x · Cited by 105 · see citing works
Gellerich, F. N., Bohnensack, R., & Kunz, W. (1983) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/0005-2728(83)90086-5 · Cited by 101 · see citing works
Control of mitochondrial metabolism by the ATPADP ratio
Davis, E. J., & Thienen, W. I. A. D.-V. (1978) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(78)91357-8 · Cited by 92 · see citing works
Relationship between chemiosmotic flows and thermodynamic forces in oxidative phosphorylation
DAM, K. V., Westerhoff, H. V., Krab, K., et al. (1980) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/0005-2728(80)90156-5 · Cited by 83 · see citing works
Souverijn, J. H. M., Huisman, L. A., Rosing, J., & Kemp, A. (1973) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/0005-2728(73)90168-0 · Cited by 80 · see citing works
Bohnensack, R., Küster, U., & Letko, G. (1982) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/0005-2728(82)90139-6 · Cited by 61 · see citing works
WANDERS, R. J. A., Groen, A. K., Meijer, A. J., et al. (1981) · FEBS Letters · doi:10.1016/0014-5793(81)81160-x · Cited by 48 · see citing works
Self-citationControl of mitochondrial respiration
Tager, J. M., Groen, A. K., Wanders, R. J. A., et al. (1983) · Biochemical Society Transactions · doi:10.1042/bst0110040 · Cited by 44 · see citing works
Self-citationKüster, U., Letko, G., Kunz, W., et al. (1981) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/0005-2728(81)90072-4 · Cited by 43 · see citing works
Investigation of the dependence of the intramitochondrial [ATP]/[ADP] ratio on the respiration rate
Letko, G., Küster, U., Duszyński, J., et al. (1980) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/0005-2728(80)90057-2 · Cited by 41 · see citing works
WANDERS, R. J. A., WOERKOM, G. M. V., NOOTEBOOM, R. F., et al. (1981) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1981.tb05066.x · Cited by 35 · see citing works
Self-citationRelation between extra- and intramitochondrial ATPADP ratios in rat liver mitochondria
Brawand, F., Folly, G., & Walter, P. (1980) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/0005-2728(80)90199-1 · Cited by 35 · see citing works
Westerhoff, H. V., Groen, A. K., & Wanders, R. J. A. (1983) · Biochemical Society Transactions · doi:10.1042/bst0110090 · Cited by 21 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 9
- Groen, A. K., Van der Meer, R., Westerhoff, H. V., Wanders, R. J. A., Akerboom, T. P. M. & Tager, J. M. (1982) in Metabolic Comnpartmentation (Sies, H., ed.) pp. 9-37, Academic Press, New York.
- Kacser, H. & Burns, J. A. (1973) in Rate Coiitro1 of Biological Processes (Davies, D. D., ed.) pp. 65 -104, Cambridge University Press, London.
- Kacser, H. & Burns, J. A. (1979) Biochem. Soc. Trans. 7, 1149- 11 60.
- Groen, A. K., Wanders, R. J. A,, Van Roermund, C., Westerhoff, H. V. & Tager, J. M. (1982) in Short Reports of the Second European Bioenergetics Conjerence, pp. 565 -566, LBTM- CNRS, Villeurbanne.
- rager, J. M., Groen, A. K., Wanders, R. J. A., Duszynski, J., Westerhoff, H. V. & Vervoorn, R. C. (1983) Biochenz. Soc. Trans. 11, 40-43.
- Tager, J. M., Groen, A. K., Wanders, R. J. A., Duszynski, J., Westerhoff, H. V. & Vervoorn, R. C. (1983) in Isolation, Characterization and Use of Hepatocytes (Harris, R. A. & Cornell, N. W., eds) pp. 31 3-322, Elsevier, New York.
- Wanders, R. J. A., Groen, A. K., Meijer, A. J . & Tager, J. M. Williamson, J. R. & Corkey, B. E. (1969) Methods Enzymol. 13, Bergmeyer, H. U. (ed.) (1 974) Methods of Enzymatic Analysis, 2nd Engl. edn, Verlag Chemie/Academic Press, Weinheim/New York.
- Westerhoff, H. V. (1983) Ph. D. Thesis, University of Amsterdam.
- Westerhoff, H. V., Groen, A. K. & Wanders, R. J. A. (1983) Biochem. Soc. Trans. 11, 90-91. 2455. Biophys. Res. Commun. 83, 1260 -1266. (1981) FEBS Lett. 132, 201 -206. 434 -51 3. 590, 285 -289.
Cited by
Sorted by citations
Mitochondrial Dysfunction Induced by Sertraline, an Antidepressant Agent
Li, Y., Couch, L., Higuchi, M., Fang, J.-L., & Guo, L. (2012) · Toxicological Sciences · doi:10.1093/toxsci/kfs100 · Cited by 120 · see citing works
Oxaloacetic acid mediates ADP-dependent inhibition of mitochondrial complex II-driven respiration
Fink, B. D., Bai, F., Yu, L., Sheldon, R. D., Sharma, A., Taylor, E. B., & Sivitz, W. I. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.005144 · Cited by 54 · see citing works
- Authors
- WANDERS, R. J. A., GROEN, A. K., VAN ROERMUND, C. W. T., & TAGER, J. M.
- Affiliations
- University of Amsterdam (NL)
- Venue
- European Journal of Biochemistry
- Publisher
- Wiley
- Published
- 1984-07
- Volume
- 142
- Issue
- 2
- Pages
- 417-424
- ISSN
- 0014-2956 (ISSN-L)
- 1432-1033
- OpenAlex
- W1992056356
- Cited by
- 93
- References
- 28
- Citations by year
- 2025: 1 · 2023: 2 · 2022: 3 · 2021: 1 · 2018: 4 · 2017: 5 · 2016: 3 · 2015: 2 · 2013: 2 · 2012: 2
- FWCI
- 2.74
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- European Journal of Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › ATP Synthase and ATPases Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- adenine nucleotide translocase, oxidative phosphorylation, flux control coefficients, elastic constants, creatine kinase, hexokinase, ATP/ADP ratio, carboxyatractyloside, rat liver mitochondria, succinate respiration, metabolic control analysis
- MeSH terms
- Mitochondrial ADP, ATP Translocases, Adenosine Diphosphate, Adenosine Triphosphate, Animals, Creatine, Creatine Kinase, Glucose, Hexokinase, Male, Mathematics, Mitochondria, Liver, Nucleotidyltransferases, Oxidative Phosphorylation, Oxygen Consumption, Rats, Inbred Strains, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
