Biology:Glycine dehydrogenase (decarboxylating)
 Generic protein structure example |
| glycine decarboxylase | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| EC number | 1.4.4.2 | ||||||||
| CAS number | 37259-67-9 | ||||||||
| Databases | |||||||||
| IntEnz | IntEnz view | ||||||||
| BRENDA | BRENDA entry | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
| Gene Ontology | AmiGO / QuickGO | ||||||||
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Glycine decarboxylase also known as glycine cleavage system P protein or glycine dehydrogenase is an enzyme that in humans is encoded by the GLDC gene.[1][2][3]
Reaction
Glycine decarboxylase (EC 1.4.4.2) is an enzyme that catalyzes the following chemical reaction:
- glycine + H-protein-lipoyllysine [math]\displaystyle{ \rightleftharpoons }[/math] H-protein-S-aminomethyldihydrolipoyllysine + CO2
Thus, the two substrates of this enzyme are glycine and H-protein-lipoyllysine, whereas its two products are H-protein-S-aminomethyldihydrolipoyllysine and CO2.[4]
This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-NH2 group of donors with a disulfide as acceptor. This enzyme participates in glycine, serine and threonine metabolism. It employs one cofactor, pyridoxal phosphate.
Function
Glycine decarboxylase is the P-protein of the glycine cleavage system in eukaryotes. The glycine cleavage system catalyzes the degradation of glycine. The P protein binds the alpha-amino group of glycine through its pyridoxal phosphate cofactor. Carbon dioxide is released and the remaining methylamine moiety is then transferred to the lipoamide cofactor of the H protein.
Degradation of glycine is brought about by the glycine cleavage system, which is composed of four mitochondrial protein components: P protein (a pyridoxal phosphate-dependent glycine decarboxylase), H protein (a lipoic acid-containing protein), T protein (a tetrahydrofolate-requiring enzyme), and L protein (a lipoamide dehydrogenase).[3]
Clinical significance
Glycine encephalopathy is due to defects in GLDC or AMT of the glycine cleavage system.[3]
References
- ↑ "The glycine cleavage system. Molecular cloning of the chicken and human glycine decarboxylase cDNAs and some characteristics involved in the deduced protein structures". J Biol Chem 266 (5): 3323–9. Mar 1991. doi:10.1016/S0021-9258(18)49991-7. PMID 1993704.
- ↑ "Structural and expression analyses of normal and mutant mRNA encoding glycine decarboxylase: three-base deletion in mRNA causes nonketotic hyperglycinemia". Biochem Biophys Res Commun 174 (3): 1176–82. Mar 1991. doi:10.1016/0006-291X(91)91545-N. PMID 1996985.
- ↑ 3.0 3.1 3.2 "Entrez Gene: GLDC glycine dehydrogenase (decarboxylating)". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2731.
- ↑ Kikuchi G (2008). "The glycine cleavage system: reaction mechanism, physiological significance, and hyperglycinemia". Proc. Jpn. Acad. Ser. B Phys. Biol. Sci. 84 (7): 246–63. doi:10.2183/pjab.84.246. PMID 18941301. Bibcode: 2008PJAB...84..246K.
Further reading
- "The mitochondrial glycine cleavage system. Functional association of glycine decarboxylase and aminomethyl carrier protein". J. Biol. Chem. 255 (24): 11671–6. 1980. doi:10.1016/S0021-9258(19)70184-7. PMID 7440563.
- Perham RN (2000). "Swinging arms and swinging domains in multifunctional enzymes: catalytic machines for multistep reactions". Annu. Rev. Biochem. 69: 961–1004. doi:10.1146/annurev.biochem.69.1.961. PMID 10966480.
- "Expression, purification, and physical characterization of Escherichia coli lipoyl(octanoyl)transferase". Protein Expr. Purif. 39 (2): 269–82. 2005. doi:10.1016/j.pep.2004.10.021. PMID 15642479.*"Nonketotic hyperglycinemia (glycine encephalopathy): laboratory diagnosis". Mol. Genet. Metab. 74 (1–2): 139–46. 2001. doi:10.1006/mgme.2001.3224. PMID 11592811.
- "Identification of a common mutation in Finnish patients with nonketotic hyperglycinemia". J. Clin. Invest. 90 (1): 160–4. 1992. doi:10.1172/JCI115831. PMID 1634607.
- "One of the two genomic copies of the glycine decarboxylase cDNA has been deleted at a 5' region in a patient with nonketotic hyperglycinemia". Biochem. Biophys. Res. Commun. 173 (3): 801–6. 1991. doi:10.1016/S0006-291X(05)80858-7. PMID 2268343.
- "Nonketotic hyperglycinemia in a patient with the 9p- syndrome". Am. J. Med. Genet. 32 (4): 504–5. 1989. doi:10.1002/ajmg.1320320416. PMID 2773994.
- "Purification and properties of glycine decarboxylase, a component of the glycine cleavage system, from rat liver mitochondria and immunochemical comparison of this enzyme from various sources". J. Biochem. 88 (4): 1193–9. 1981. doi:10.1093/oxfordjournals.jbchem.a133074. PMID 6778858.
- "Defective glycine cleavage system in nonketotic hyperglycinemia. Occurrence of a less active glycine decarboxylase and an abnormal aminomethyl carrier protein". J. Clin. Invest. 68 (2): 525–34. 1981. doi:10.1172/JCI110284. PMID 6790577.
- "Human glycine decarboxylase gene (GLDC) and its highly conserved processed pseudogene (psiGLDC): their structure and expression, and the identification of a large deletion in a family with nonketotic hyperglycinemia". Hum. Genet. 106 (3): 298–305. 2000. doi:10.1007/s004390051041. PMID 10798358.
- "Biochemical and molecular investigations of patients with nonketotic hyperglycinemia". Mol. Genet. Metab. 70 (2): 116–21. 2000. doi:10.1006/mgme.2000.3000. PMID 10873393.
- "Recurrent mutations in P- and T-proteins of the glycine cleavage complex and a novel T-protein mutation (N145I): a strategy for the molecular investigation of patients with nonketotic hyperglycinemia (NKH)". Mol. Genet. Metab. 72 (4): 322–5. 2001. doi:10.1006/mgme.2001.3158. PMID 11286506.
- "Heterozygous GLDC and GCSH gene mutations in transient neonatal hyperglycinemia". Ann. Neurol. 52 (5): 643–6. 2002. doi:10.1002/ana.10367. PMID 12402263.
- "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. 2003. doi:10.1073/pnas.242603899. PMID 12477932. Bibcode: 2002PNAS...9916899M.
- "Gene Symbol: GLDC. Disease: NKH glycine encephalopathy". Hum. Genet. 113 (5): 465. 2003. doi:10.1007/s00439-003-1014-5. PMID 14552331.
- "Glycine decarboxylase mutations: a distinctive phenotype of nonketotic hyperglycinemia in adults". Neurology 64 (7): 1255–7. 2006. doi:10.1212/01.WNL.0000156800.23776.40. PMID 15824356.
- "Mild glycine encephalopathy (NKH) in a large kindred due to a silent exonic GLDC splice mutation". Neurology 64 (8): 1426–30. 2006. doi:10.1212/01.WNL.0000158475.12907.D6. PMID 15851735.
- "A single nucleotide substitution that abolishes the initiator methionine codon of the GLDC gene is prevalent among patients with glycine encephalopathy in Jerusalem". J. Hum. Genet. 50 (5): 230–4. 2005. doi:10.1007/s10038-005-0243-y. PMID 15864413.
- "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes". Genome Res. 16 (1): 55–65. 2006. doi:10.1101/gr.4039406. PMID 16344560.
- "Treatment from birth of nonketotic hyperglycinemia due to a novel GLDC mutation". Ann. Neurol. 59 (2): 411–5. 2006. doi:10.1002/ana.20759. PMID 16404748.
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