PDK4

Pyruvate dehydrogenase kinase, isozyme 4
Rendering based on PDB 2E0A.
Available structures PDB 2E0A, 2ZDX, 2ZDY, 2ZKJ, 3D2R
Identifiers
Symbols	PDK4; FLJ40832
External IDs	OMIM: 602527 MGI: 1351481 HomoloGene: 38109 GeneCards: PDK4 Gene
EC number	2.7.11.2
Gene Ontology Molecular function • two-component sensor activity • nucleotide binding • protein kinase activity • pyruvate dehydrogenase (acetyl-transferring) kinase activity • ATP binding • transferase activity Cellular component • mitochondrion • mitochondrial inner membrane • mitochondrial matrix Biological process • carbohydrate metabolic process • glucose metabolic process • pyruvate metabolic process • protein phosphorylation • protein phosphorylation • regulation of acetyl-CoA biosynthetic process from pyruvate • peptidyl-histidine phosphorylation Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	5166	27273
Ensembl	ENSG00000004799	ENSMUSG00000019577
UniProt	Q16654	Q544J2
RefSeq (mRNA)	NM_002612	NM_013743.2
RefSeq (protein)	NP_002603	NP_038771.1
Location (UCSC)	Chr 7: 95.21 – 95.23 Mb	Chr 6: 5.43 – 5.45 Mb
PubMed search	[1]	[2]

[Pyruvate dehydrogenase [lipoamide]] kinase isozyme 4, mitochondrial is an enzyme that in humans is encoded by the PDK4 gene.^[1][2] It codes for an isozyme of pyruvate dehydrogenase kinase.

This gene is a member of the PDK/BCKDK protein kinase family and encodes a mitochondrial protein with a histidine kinase domain. This protein is located in the matrix of the mitrochondria and inhibits the pyruvate dehydrogenase complex by phosphorylating one of its subunits, reducing the conversion of pyruvate, which is produced from the oxidation of glucose and amino acids, to acetyl-CoA and contributing to the regulation of glucose metabolism. Expression of this gene is regulated by glucocorticoids, retinoic acid and insulin.^[2] PDK4 is increased in hibernation and helps to decrease metabolism and conserve glucose by decreasing its conversion to acetyl-CoA, which enters the citric acid cycle and is converted to ATP.^[3]

Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles.^[4]

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Citric_acid_cycle edit

References

1. ^ Gudi R, Bowker-Kinley MM, Kedishvili NY, Zhao Y, Popov KM (Jan 1996). "Diversity of the pyruvate dehydrogenase kinase gene family in humans". J Biol Chem 270 (48): 28989–94. doi:10.1074/jbc.270.48.28989. PMID 7499431. 
2. ^ ^{a b} "Entrez Gene: PDK4 pyruvate dehydrogenase kinase, isozyme 4". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5166. 
3. ^ Andrews MT, Squire TL, Bowen CM, Rollins MB (Jul 1998). "Low-temperature carbon utilization is regulated by novel gene activity in the heart of a hibernating mammal". Proc Natl Acad Sci U S A 95 (14): 8392–7. doi:10.1073/pnas.95.14.8392. PMC 20986. PMID 9653197. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=20986. 
4. ^ The interactive pathway map can be edited at WikiPathways: "TCACycle_WP78". http://www.wikipathways.org/index.php/Pathway:WP78. 

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. doi:10.1152/ajpendo.00526.2002. PMID 12676647. 
• Kwon HS, Harris RA (2005). "Mechanisms responsible for regulation of pyruvate dehydrogenase kinase 4 gene expression". Adv Enzyme Regul 44: 109–21. doi:10.1016/j.advenzreg.2003.11.020. PMID 15581486. 
• Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298. 
• Rowles J, Scherer SW, Xi T, et al. (1996). "Cloning and characterization of PDK4 on 7q21.3 encoding a fourth pyruvate dehydrogenase kinase isoenzyme in human". J Biol Chem 271 (37): 22376–82. doi:10.1074/jbc.271.37.22376. PMID 8798399. 
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149. 
• Majer M, Popov KM, Harris RA, et al. (1998). "Insulin downregulates pyruvate dehydrogenase kinase (PDK) mRNA: potential mechanism contributing to increased lipid oxidation in insulin-resistant subjects". Mol Genet Metab 65 (2): 181–6. doi:10.1006/mgme.1998.2748. PMID 9787110. 
• Pilegaard H, Ordway GA, Saltin B, Neufer PD (2000). "Transcriptional regulation of gene expression in human skeletal muscle during recovery from exercise". Am J Physiol Endocrinol Metab 279 (4): E806–14. PMID 11001762. 
• 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. doi:10.1042/0264-6021:3580069. PMC 1222033. PMID 11485553. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1222033. 
• 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. doi:10.1074/jbc.M103069200. PMID 11486000. 
• Peters SJ, Harris RA, Wu P, et al. (2002). "Human skeletal muscle PDH kinase activity and isoform expression during a 3-day high-fat/low-carbohydrate diet". Am J Physiol Endocrinol Metab 281 (6): E1151–8. PMID 11701428. 
• 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. doi:10.1042/BJ20020301. PMC 1222743. PMID 11978179. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1222743. 
• Razeghi P, Young ME, Ying J, et al. (2002). "Downregulation of metabolic gene expression in failing human heart before and after mechanical unloading". Cardiology 97 (4): 203–9. doi:10.1159/000063122. PMID 12145475. 
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc Natl Acad Sci U S A 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241. 
• Boulatnikov I, Popov KM (2003). "Formation of functional heterodimers by isozymes 1 and 2 of pyruvate dehydrogenase kinase". Biochim Biophys Acta 1645 (2): 183–92. PMID 12573248. 
• Rosa G, Di Rocco P, Manco M, et al. (2003). "Reduced PDK4 expression associates with increased insulin sensitivity in postobese patients". Obes Res 11 (2): 176–82. doi:10.1038/oby.2003.28. PMID 12582211. 
• Pilegaard H, Saltin B, Neufer PD (2003). "Effect of short-term fasting and refeeding on transcriptional regulation of metabolic genes in human skeletal muscle". Diabetes 52 (3): 657–62. doi:10.2337/diabetes.52.3.657. PMID 12606505. 
• Scherer SW, Cheung J, MacDonald JR, et al. (2003). "Human chromosome 7: DNA sequence and biology". Science 300 (5620): 767–72. doi:10.1126/science.1083423. PMC 2882961. PMID 12690205. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2882961. 
• Hillier LW, Fulton RS, Fulton LA, et al. (2003). "The DNA sequence of human chromosome 7". Nature 424 (6945): 157–64. doi:10.1038/nature01782. PMID 12853948.