Phosphoenolpyruvate carboxykinase
| Phosphoenolpyruvate carboxykinase 1 (cytosolic) | ||
|---|---|---|
|
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| Belt / surface model of the PEPCK-C according to PDB 1KHF . Bound PEP is highlighted as a dome. | ||
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Existing structural data: s. UniProt |
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| Properties of human protein | ||
| Mass / length primary structure | 622 amino acids | |
| Cofactor | manganese | |
| Identifier | ||
| Gene name | PCK1 | |
| External IDs | ||
| Enzyme classification | ||
| EC, category | 4.1.1.32 , lyase | |
| Response type | Phosphorylative decarboxylation | |
| Substrate | GTP + oxaloacetate | |
| Products | GDP + phosphoenolpyruvate + CO 2 | |
| Occurrence | ||
| Homology family | PEPCK (GTP) | |
| Parent taxon | Creature | |
| Exceptions | plants | |
| Orthologue | ||
| human | House mouse | |
| Entrez | 5105 | 18534 |
| Ensemble | ENSMUSG00000027513 | |
| UniProt | P35558 | Q9Z2V4 |
| Refseq (mRNA) | NM_002591 | NM_011044 |
| Refseq (protein) | NP_002582 | NP_035174 |
| Gene locus | Chr 20: 57.56 - 57.57 Mb | Chr 2: 173.15 - 173.16 Mb |
| PubMed search | 5105 |
18534
|
| Phosphoenolpyruvate carboxykinase 2 (mitochondrial) | ||
|---|---|---|
| Properties of human protein | ||
| Mass / length primary structure | 608 amino acids | |
| Cofactor | manganese | |
| Identifier | ||
| Gene name | PCK2 | |
| External IDs | ||
| Orthologue | ||
| human | House mouse | |
| Entrez | 5106 | 74551 |
| Ensemble | ENSG00000100889 | ENSMUSG00000040618 |
| UniProt | Q16822 | Q8BH04 |
| Refseq (mRNA) | NM_004563 | NM_028994 |
| Refseq (protein) | NP_004554 | NP_083270 |
| Gene locus | Chr 14: 24.09 - 24.1 Mb | Chr 14: 55.54 - 55.55 Mb |
| PubMed search | 5106 |
74551
|
Phosphoenolpyruvate carboxykinase [GTP] (abbr .: PEPCK) is that of the enzyme that catalyzes the conversion of oxaloacetate by GTP to phosphoenolpyruvate catalyzed . This reaction step is the rate-determining sub-step of gluconeogenesis . PEPCK is also found in bacteria, in vertebrates there are two isoforms , cytosolic and mitochondrial. They are encoded in humans by the genes PCK1 and PCK2 and are particularly expressed in the liver , kidneys and adipocytes . In contrast to PEPCK-M, the activity of PEPCK-C can be regulated by hormones. Mutations in PCK1 or PCK2 can cause the corresponding (rare) PEPCK deficiency disease.
The PEPCK [GTP] is not to be confused with the ATP-dependent PEPCK, which occurs in plants and bacteria, but not in animals.
Because of its central position in gluconeogenesis, the PEPCK is a candidate when it comes to hereditary diabetes or obesity.
Catalyzed reaction
GTP + GDP + + CO 2
A phosphate group is transferred from GTP to oxaloacetate and carbon dioxide is split off. In the active center of the enzyme there is an arginine residue and the metal manganese in oxidation state + II. The keto oxygen forms a complex between arginine and Mn 2+ and thus enables the carboxy group to be split off at the end further away with the formation of a double bond. A phosphate is then transferred from GTP to the oxygen. At the same time, Mn 2+ and arginine also ensure the complexation of GTP in the enzyme.
regulation
The activity of PEPCK-C, and thus gluconeogenesis as a whole, is influenced by a number of hormones . Glucagon promotes the transcription of PEPCK by phosphorylation of a transcription factor in the liver , just like all-trans retinoic acid . Other regulating molecules are liver lipids , insulin (via SREBP -1c) and γ- interferon .
For regulation by glucocorticoids, see the detailed example there.
literature
- Reynolds CH: Activation and inactivation of phosphoenolpyruvate carboxykinase by ferrous ions . In: Biochem. J. . 185, No. 2, February 1980, pp. 451-4. PMID 7396825 . PMC 1161372 (free full text).
Individual evidence
- ↑ UniProt P35558 , UniProt Q16822
- ↑ Beale EG, Harvey BJ, Forest C: PCK1 and PCK2 as candidate diabetes and obesity genes . In: Cell Biochem. Biophys. . 48, No. 2-3, 2007, pp. 89-95. PMID 17709878 .
- ^ LW Tari: Structure and Mechanism of Phosphoenolpyruvate Carboxykinase. In: Journal of Biological Chemistry. 272, pp. 8105-8108, doi : 10.1074 / jbc.272.13.8105 .
- ↑ Christ B: Inhibition of glucagon signaling and downstream actions by interleukin 1beta and tumor necrosis factor alpha in cultured primary rat hepatocytes . In: Horm. Metab. Res. . 40, No. 1, January 2008, pp. 18-23. PMID 18335579 .
- ↑ Cadoudal T, Glorian M, Massias A, Fouque F, Forest C, Benelli C: Retinoids upregulate phosphoenolpyruvate carboxykinase and glyceroneogenesis in human and rodent adipocytes . In: J. Nutr. . 138, No. 6, June 2008, pp. 1004-9. PMID 18492826 .
- ↑ Chen G: Liver lipid molecules induce PEPCK-C gene transcription and attenuate insulin action . In: Biochem. Biophys. Res. Commun. . 361, No. 3, September 2007, pp. 805-10. doi : 10.1016 / j.bbrc.2007.07.108 . PMID 17678617 .
- ↑ Chakravarty K, Hanson RW: Insulin regulation of phosphoenolpyruvate carboxykinase-c gene transcription: the role of sterol regulatory element-binding protein 1c . In: Nutr. Rev. . 65, No. 6 Pt 2, June 2007, pp. S47-56. doi : 10.1111 / j.1753-4887.2007.tb00328.x . PMID 17605314 .
- ↑ Khazen W, Distel E, Collinet M, et al : Acute and selective inhibition of adipocyte glyceroneogenesis and cytosolic phosphoenolpyruvate carboxykinase by interferon gamma . In: Endocrinology . 148, No. 8, August 2007, pp. 4007-14. doi : 10.1210 / en.2006-1760 . PMID 17495004 .
