The DOI matches its Crossref record.
Recent advances in mechanisms regulating glucose oxidation at the level of the pyruvate dehydrogenase complex by PDKs
Abstract
The mitochondrial pyruvate dehydrogenase complex (PDC) catalyzes the oxidative decarboxylation of pyruvate, linking glycolysis to the tricarboxylic acid cycle and fatty acid (FA) synthesis. Knowledge of the mechanisms that regulate PDC activity is important, because PDC inactivation is crucial for glucose conservation when glucose is scarce, whereas adequate PDC activity is required to allow both ATP and FA production from glucose. The mechanisms that control mammalian PDC activity include its phosphorylation (inactivation) by a family of pyruvate dehydrogenase kinases (PDKs 1–4) and its dephosphorylation (activation, reactivation) by the pyruvate dehydrogenase phosphate phosphatases (PDPs 1 and 2). Isoform-specific differences in kinetic parameters, regulation, and phosphorylation site specificity of the PDKs introduce variations in the regulation of PDC activity in differing endocrine and metabolic states. In this review, we summarize recent significant advances in our knowledge of the mechanisms regulating PDC with emphasis on the PDKs, in particular PDK4, whose expression is linked with sustained changes in tissue lipid handling and which may represent an attractive target for pharmacological interventions aimed at modulating whole body glucose, lipid, and lactate homeostasis in disease states.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
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?
In the citing paper
“PDH is the enzyme responsible for converting pyruvate to acetyl-CoA and is a central metabolic node.35”
From (Pro)renin Receptor Inhibition Reprograms Hepatic Lipid Metabolism and Protects Mice From Diet-Induced Obesity and Hepatosteatosis (2018) · cites this paper as [35]
Citations
Cites
No references could be resolved yet.
Research works printed but not linked: 72
- 10.1172/JCI9056 · DOI
- 10.1042/bj3440047 · DOI
- 10.1042/bj3290191 · DOI
- 10.1074/jbc.273.37.23786 · DOI
- 10.1006/abbi.1998.0627 · DOI
- 10.1016/S0952-3278(99)80009-X · DOI
- 10.1172/JCI3949 · DOI · Paper page
- 10.1210/endo.142.10.8458 · DOI
- 10.1042/bj2340233 · DOI
- 10.1172/JCI0214080 · DOI
- 10.1074/jbc.270.48.28989 · DOI
- 10.1073/pnas.91.23.11012 · DOI
- 10.1042/bj20020754 · DOI
- 10.2337/diabetes.49.5.775 · DOI
- 10.1042/bj2520325 · DOI
- 10.1042/bj20011841 · DOI
- 10.1042/bj2580529 · DOI
- 10.1074/jbc.273.28.17680 · DOI
- 10.2337/diabetes.51.2.276 · DOI
- 10.1152/ajpendo.1985.248.5.E567 · DOI
- 10.1089/dna.1997.16.335 · DOI
- 10.1042/bj1540327 · DOI
- 10.1038/35013000 · DOI · Paper page
- 10.1172/JCI6223 · DOI · Paper page
- 10.1042/bj3580069 · DOI
- 10.1074/jbc.270.24.14297 · DOI
- 10.1074/jbc.M103069200 · DOI · Paper page
- 10.1021/bi00086a002 · DOI
- 10.1074/jbc.272.50.31625 · DOI
- 10.1073/pnas.96.13.7473 · DOI · Paper page
- 10.1073/pnas.62.1.234 · DOI
- 10.1042/bj2670245 · DOI
- 10.1074/jbc.273.27.16710 · DOI
- 10.1074/jbc.M203997200 · DOI
- 10.1016/0014-5793(93)80864-Q · DOI
- 10.1152/ajpregu.2001.280.3.R661 · DOI
- 10.1152/ajpendo.2001.281.6.E1151 · DOI
- 10.1016/0006-291X(72)90448-2 · DOI
- 10.1016/S1040-7952(97)80012-2 · DOI
- Popov KM, 1994, J Biol Chem, 269, 29720, 10.1016/S0021-9258(18)43940-3 · DOI
- Popov KM, 1993, J Biol Chem, 268, 26602, 10.1016/S0021-9258(19)74354-3 · DOI
- 10.1111/j.1432-1033.1982.tb06690.x · DOI
- 10.1016/0014-5793(96)00877-0 · DOI
- 10.1074/jbc.271.37.22376 · DOI
- 10.1111/j.1432-1033.1981.tb05733.x · DOI
- 10.1016/0167-4889(92)90137-Z · DOI
- 10.1074/jbc.M104285200 · DOI
- 10.2337/diabetes.50.12.2729 · DOI
- 10.1006/abbi.2001.2586 · DOI
- 10.1042/bj20011699 · DOI
- 10.1042/bst0290272 · DOI
- 10.1042/bj2620669 · DOI
- 10.1096/fasebj.8.1.8299890 · DOI
- 10.1042/bj3460651 · DOI
- 10.1042/bj3520731 · DOI
- 10.1021/bi00265a031 · DOI
- 10.1016/0006-291X(79)91672-3 · DOI
- 10.1042/bj3490195 · DOI
- 10.1074/jbc.273.41.26618 · DOI
- 10.1042/bj2380093 · DOI
- 10.1042/bj2380083 · DOI
- 10.1016/S0952-3278(97)90491-9 · DOI
- Van der Lee KA, 2000, J Lipid Res, 41, 41, 10.1016/S0022-2275(20)32072-1 · DOI
- 10.1210/endo.142.3.8037 · DOI
- 10.1006/abbi.2000.1946 · DOI
- 10.2337/diabetes.48.8.1593 · DOI
- 10.1006/bbrc.2001.5608 · DOI
- 10.1042/bj3290197 · DOI
- 10.1073/pnas.93.10.4953 · DOI
- 10.1074/jbc.273.23.14130 · DOI
- 10.1021/bi00605a017 · DOI
- 10.1096/fj.00-0351com · DOI
Cited by
Sorted by citations
HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption
Papandreou, I., Cairns, R. A., Fontana, L., Lim, A. L., & Denko, N. C. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.01.012 · Cited by 2,267
Regulation of glucose homeostasis by glucocorticoids
Kuo, T., McQueen, A., Chen, T.-C., & Wang, J.-C. (2015) · Advances in Experimental Medicine and Biology · doi:10.1007/978-1-4939-2895-8_5 · Cited by 723
Regulation and function of the mammalian tricarboxylic acid cycle
Arnold, P. K., & Finley, L. W. S. (2023) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.102838 · Cited by 535
“While the PDHC is activated byNAD, ADP, and pyruvate, the PDKs are conversely activated by NADH, ATP, and high acetyl-CoA levels (140) (Fig.”
BackgroundMuoio, D. M., Noland, R. C., Kovalik, J.-P., Seiler, S. E., Davies, M. N., DeBalsi, K. L., Ilkayeva, O. R., Stevens, R. D., Kheterpal, I., Zhang, J., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.04.005 · Cited by 372
“…PDH activity through direct 766 Cell Metabolism 15, 764–777, May 2, 2012 ª2012 Elsevier Inc. allosteric inhibition of the enzyme complex and by stimulating a family of PDH kinases that inactive the E1a catalytic subunit via phosphorylation at multiple serine residues (Sugden and Holness, 2003).”
BackgroundWende, A. R., Huss, J. M., Schaeffer, P. J., Giguère, V., & Kelly, D. P. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.24.10684-10694.2005 · Cited by 354
Gong, B., Pan, Y., Vempati, P., Zhao, W., Knable, L., Ho, L., Wang, J., Sastre, M., Ono, K., Sauve, A. A., et al. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2012.12.005 · Cited by 345
Acetyl-CoA metabolism in cancer
Guertin, D. A., & Wellen, K. E. (2023) · Nature Reviews Cancer · doi:10.1038/s41568-022-00543-5 · Cited by 303
Boudina, S., Bugger, H., Sena, S., O'Neill, B. T., Zaha, V. G., Ilkun, O., Wright, J. J., Mazumder, P. K., Palfreyman, E., Tidwell, T. J., et al. (2009) · Circulation · doi:10.1161/circulationaha.108.792101 · Cited by 301
PGC-1α-mediated adaptations in skeletal muscle
Olesen, J., Kiilerich, K., & Pilegaard, H. (2010) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-010-0834-0 · Cited by 244
Koukourakis, M. I., Giatromanolaki, A., Sivridis, E., Gatter, K. C., & Harris, A. L. (2005) · Neoplasia · doi:10.1593/neo.04373 · Cited by 214
Gene expressions and copy numbers associated with metastatic phenotypes of uterine cervical cancer
Lyng, H., Brøvig, R. S., Svendsrud, D. H., Holm, R., Kaalhus, O., Knutstad, K., Oksefjell, H., Sundfør, K., Kristensen, G. B., & Stokke, T. (2006) · BMC Genomics · doi:10.1186/1471-2164-7-268 · Cited by 158
Illsley, N. P., Caniggia, I., & Zamudio, S. (2010) · The International Journal of Developmental Biology · doi:10.1387/ijdb.082798ni · Cited by 107
Ma, Y.-H., Wang, X., Niu, Y.-F., Yang, Z.-K., Zhang, M.-H., Wang, Z.-M., Yang, W.-D., Liu, J.-S., & Li, H.-Y. (2014) · Microbial Cell Factories · doi:10.1186/s12934-014-0100-9 · Cited by 106
“Overexpression of Brassica napus PDK in Arabidopsis repressed the PDC activity, leading to a decrease in seed oil content [10].”
BackgroundInfluentialLiu, L., Shi, X., Choi, C. S., Shulman, G. I., Klaus, K., Nair, K. S., Schwartz, G. J., Zhang, Y., Goldberg, I. J., & Yu, Y.-H. (2009) · Diabetes · doi:10.2337/db08-1096 · Cited by 66
PPARs and the orchestration of metabolic fuel selection
Sugden, M. C., Zariwala, M. G., & Holness, M. J. (2009) · Pharmacological Research · doi:10.1016/j.phrs.2009.03.014 · Cited by 64
Self-citationRen, L., Sun, Y., Lu, H., Ye, D., Han, L., Wang, N., Daugherty, A., Li, F., Wang, M., Su, F., et al. (2018) · Circulation Research · doi:10.1161/circresaha.117.312422 · Cited by 59
Warrier, M., Hinds, T. D., Ledford, K. J., Cash, H. A., Patel, P. R., Bowman, T. A., Stechschulte, L. A., Yong, W., Shou, W., Najjar, S. M., et al. (2010) · Endocrinology · doi:10.1210/en.2009-1158 · Cited by 57
Mitochondria and regulated tyrosine nitration
Koeck, T., Stuehr, D. J., & Aulak, K. S. (2005) · Biochemical Society Transactions · doi:10.1042/bst0331399 · Cited by 30
Metadata
- Authors
- Sugden, M. C., & Holness, M. J.
- Affiliations
- Department of Diabetes and Metabolic Medicine, Division of General and Developmental Medicine, Bart's and the London, Queen Mary's School of Medicine and Dentistry, University of London, London E1 4NS, United Kingdom
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2003-05-01
- Volume
- 284
- Issue
- 5
- Pages
- E855-E862
- ISSN
- 0193-1849
- 1522-1555
- Cited by
- 428
- References
- 0
- Language
- en
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
