Pyruvate dehydrogenase lipoamide kinase isozyme 1
| PDK1 | |||
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Gene ontology | |||
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| Biological process |
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| Sources:Amigo / QuickGO | |||
Ensembl | |||||||||
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| RefSeq (protein) | |||||||||
| Location (UCSC) | Chr 2: 172.56 – 172.61 Mb | Chr 2: 71.7 – 71.73 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
| View/Edit Human | View/Edit Mouse |
Pyruvate dehydrogenase lipoamide kinase isozyme 1, mitochondrial is an enzyme that in humans is encoded by the PDK1 gene.[5][6] It codes for an isozyme of pyruvate dehydrogenase kinase (PDK).
Structure
The mature protein encoded by the
Function
The Pyruvate Dehydrogenase (PDH) complex must be tightly regulated due to its central role in general metabolism. Within the complex, there are three serine residues on the E1 component that are sites for phosphorylation; this phosphorylation inactivates the complex. In humans, there have been four
Regulation
As the primary regulators of a crucial step in the central metabolic pathway, the pyruvate dehydrogenase family is tightly regulated itself by a myriad of factors. PDK activity has been shown to decrease in individuals consuming a diet that is high in
Clinical Significance
PDK1 is relevant in a variety of clinical conditions throughout the body. As PDK1 regulates the PDH complex, it has been proven to be an important regulator in certain cells, including the beta cells within the islets of the pancreas. In order to optimize glucose-stimulated insulin secretion (GSIS), a primary function of the pancreas, a low PDK1 activity must be maintained to keep PDH in a dephosphorylated and active state.[11] Maintaining low PDK1 levels has also proven to be beneficial in certain regions of the brain, as it confers a high tolerance to amyloid beta, a metabolite that is directly correlated with the development of Alzheimer's disease.[12]
Cancer
The ubiquitous role of this gene lends itself to being involved in a variety of disease pathologies, including cancer. PDK1
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000152256 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000006494 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 7499431.
- ^ a b c "Entrez Gene: PDK1 pyruvate dehydrogenase kinase, isozyme 1".
- PMID 24044887.
- PMID 11485553.
- PMID 15591305.
- PMID 17683942.
- PMID 20415663.
- PMID 22948140.
- PMID 23135628.
- PMID 18542064.
- PMID 22195962.
- PMID 16517405.
- PMID 18541534.
- PMID 24810059.
Further reading
- Sugden MC, Holness MJ (2003). "Recent advances in mechanisms regulating glucose oxidation at the level of the pyruvate dehydrogenase complex by PDKs". Am. J. Physiol. Endocrinol. Metab. 284 (5): E855–62. PMID 12676647.
- Liu S, Baker JC, Andrews PC, Roche TE (1995). "Recombinant expression and evaluation of the lipoyl domains of the dihydrolipoyl acetyltransferase component of the human pyruvate dehydrogenase complex". Arch. Biochem. Biophys. 316 (2): 926–40. PMID 7864652.
- Kolobova E, Tuganova A, Boulatnikov I, Popov KM (2001). "Regulation of pyruvate dehydrogenase activity through phosphorylation at multiple sites". Biochem. J. 358 (Pt 1): 69–77. PMID 11485553.
- Korotchkina LG, Patel MS (2001). "Site specificity of four pyruvate dehydrogenase kinase isoenzymes toward the three phosphorylation sites of human pyruvate dehydrogenase". J. Biol. Chem. 276 (40): 37223–9. PMID 11486000.
- Tuganova A, Boulatnikov I, Popov KM (2002). "Interaction between the individual isoenzymes of pyruvate dehydrogenase kinase and the inner lipoyl-bearing domain of transacetylase component of pyruvate dehydrogenase complex". Biochem. J. 366 (Pt 1): 129–36. PMID 11978179.
