The complete cDNA of PDPR, which contains 2885 base pairs, has an open reading frame of 2634 nucleotides encoding a putative presequence of 31 amino acid residues and a mature protein of 847. Characteristics of native PDPR include ability to decrease the sensitivity of the catalytic subunit to Mg2+, and reversal of this inhibitory effect by the polyamine spermine. A BLAST search of protein databases revealed that PDPr is distantly related to the mitochondrial flavoprotein dimethylglycine dehydrogenase, which functions in choline degradation.[2]
Function
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).[3]
Clinical significance
As PDPR is involved in the regulation of the central metabolic pathway, its participation in disease pathophysiology is likely, but there has been no published research on this thus far.[1]
↑Lawson, JE; Park, SH; Mattison, AR; Yan, J; Reed, LJ (12 December 1997). "Cloning, expression, and properties of the regulatory subunit of bovine pyruvate dehydrogenase phosphatase". The Journal of Biological Chemistry. 272 (50): 31625–9. doi:10.1074/jbc.272.50.31625. PMID9395502.
↑Sugden, MC; Holness, MJ (May 2003). "Recent advances in mechanisms regulating glucose oxidation at the level of the pyruvate dehydrogenase complex by PDKs". American Journal of Physiology. Endocrinology and Metabolism. 284 (5): E855–62. doi:10.1152/ajpendo.00526.2002. PMID12676647.
Further reading
Sugden, M. C.; Holness, M. J. (2003). "Recent advances in mechanisms regulating glucose oxidation at the level of the pyruvate dehydrogenase complex by PDKs". American Journal of Physiology. Endocrinology and Metabolism. 284 (5): E855–62. doi:10.1152/ajpendo.00526.2002. PMID12676647.
Ohara, O; Nagase, T; Mitsui, G; Kohga, H; Kikuno, R; Hiraoka, S; Takahashi, Y; Kitajima, S; Saga, Y; Koseki, H (2002). "Characterization of size-fractionated cDNA libraries generated by the in vitro recombination-assisted method". DNA research : an international journal for rapid publication of reports on genes and genomes. 9 (2): 47–57. doi:10.1093/dnares/9.2.47. PMID12056414.
Lawson, J. E.; Park, S. H.; Mattison, A. R.; Yan, J; Reed, L. J. (1997). "Cloning, expression, and properties of the regulatory subunit of bovine pyruvate dehydrogenase phosphatase". The Journal of Biological Chemistry. 272 (50): 31625–9. doi:10.1074/jbc.272.50.31625. PMID9395502.
