Glycine dehydrogenase (decarboxylating)

GLDC
Identifiers
Aliases	GLDC , GCE, GCSP, HYGN1, Glycine dehydrogenase, glycine decarboxylase
External IDs	OMIM: 238300; MGI: 1341155; HomoloGene: 141; GeneCards: GLDC; OMA:GLDC - orthologs
Gene location (Human) Chr. Chromosome 9 (human) [1] Band 9p24.1 Start 6,532,467 bp [1] End 6,645,729 bp [1]
Gene location (Mouse) Chr. Chromosome 19 (mouse) [2] Band 19 C1|19 24.87 cM Start 30,075,847 bp [2] End 30,152,829 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right lobe of liver kidney tubule gonad human kidney ventricular zone sural nerve placenta metanephric glomerulus testicle embryo Top expressed in otic placode otic vesicle yolk sac morula primitive streak morula epiblast left lobe of liver right kidney ciliary body More reference expression data BioGPS More reference expression data
Gene ontology Molecular function lyase activity electron transfer activity oxidoreductase activity catalytic activity pyridoxal phosphate binding protein dimerization activity glycine binding glycine dehydrogenase (decarboxylating) activity protein homodimerization activity pyridoxal binding enzyme binding Cellular component mitochondrial matrix plasma membrane nucleus glycine cleavage complex mitochondrion Biological process cellular amino acid metabolic process glycine metabolic process glycine decarboxylation via glycine cleavage system glycine catabolic process response to methylamine response to lipoic acid cellular response to leukemia inhibitory factor electron transport chain Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 2731 104174 Ensembl ENSG00000178445 ENSMUSG00000024827 UniProt P23378 Q91W43 RefSeq (mRNA) NM_000170 NM_138595 RefSeq (protein) NP_000161 NP_613061 Location (UCSC) Chr 9: 6.53 – 6.65 Mb Chr 19: 30.08 – 30.15 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

glycine decarboxylase
Identifiers
EC no.	1.4.4.2
CAS no.	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
Search PMC articles PubMed articles NCBI proteins

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. ^{[5] [6] [7]}

Reaction

Glycine decarboxylase (EC 1.4.4.2) is an enzyme that catalyzes the following chemical reaction:

glycine + H-protein-lipoyllysine ⇌ 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. ^[8]

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). ^[7]

Clinical significance

Glycine encephalopathy is due to defects in GLDC or AMT of the glycine cleavage system. ^[7]

References

1. GRCh38: Ensembl release 89: ENSG00000178445 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000024827 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Kume A, Koyata H, Sakakibara T, Ishiguro Y, Kure S, Hiraga K (Mar 1991). "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. doi: 10.1016/S0021-9258(18)49991-7 . PMID   1993704.
6. Kure S, Narisawa K, Tada K (Mar 1991). "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. Bibcode:1991BBRC..174.1176K. doi:10.1016/0006-291X(91)91545-N. PMID   1996985.
7. "Entrez Gene: GLDC glycine dehydrogenase (decarboxylating)".
8. 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. Bibcode:2008PJAB...84..246K. doi:10.2183/pjab.84.246. PMC   3666648 . PMID   18941301.

Further reading

• Hiraga K, Kikuchi G (1980). "The mitochondrial glycine cleavage system. Functional association of glycine decarboxylase and aminomethyl carrier protein". J. Biol. Chem. 255 (24): 11671–6. 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.
• Broadwater JA, Haas JA, Fox BG, Booker SJ (2005). "Expression, purification, and physical characterization of Escherichia coli lipoyl(octanoyl)transferase". Protein Expr. Purif. 39 (2): 269–82. doi:10.1016/j.pep.2004.10.021. PMID   15642479.*Applegarth DA, Toone JR (2001). "Nonketotic hyperglycinemia (glycine encephalopathy): laboratory diagnosis". Mol. Genet. Metab. 74 (1–2): 139–46. doi:10.1006/mgme.2001.3224. PMID   11592811.
• Kure S, Takayanagi M, Narisawa K, et al. (1992). "Identification of a common mutation in Finnish patients with nonketotic hyperglycinemia". J. Clin. Invest. 90 (1): 160–4. doi:10.1172/JCI115831. PMC   443076 . PMID   1634607.
• Sakakibara T, Koyata H, Ishiguro Y, et al. (1991). "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. doi:10.1016/S0006-291X(05)80858-7. PMID   2268343.
• Burton BK, Pettenati MJ, Block SM, et al. (1989). "Nonketotic hyperglycinemia in a patient with the 9p- syndrome". Am. J. Med. Genet. 32 (4): 504–5. doi:10.1002/ajmg.1320320416. PMID   2773994.
• Hayasaka K, Kochi H, Hiraga K, Kikuchi G (1981). "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. doi:10.1093/oxfordjournals.jbchem.a133074. PMID   6778858.
• Hiraga K, Kochi H, Hayasaka K, et al. (1981). "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. doi:10.1172/JCI110284. PMC   370827 . PMID   6790577.
• Takayanagi M, Kure S, Sakata Y, et al. (2000). "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. doi:10.1007/s004390051041 (inactive 5 July 2025). PMID   10798358.
• Toone JR, Applegarth DA, Coulter-Mackie MB, James ER (2000). "Biochemical and molecular investigations of patients with nonketotic hyperglycinemia". Mol. Genet. Metab. 70 (2): 116–21. doi:10.1006/mgme.2000.3000. PMID   10873393.
• Toone JR, Applegarth DA, Coulter-Mackie MB, James ER (2001). "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. doi:10.1006/mgme.2001.3158. PMID   11286506.
• Kure S, Kojima K, Ichinohe A, et al. (2002). "Heterozygous GLDC and GCSH gene mutations in transient neonatal hyperglycinemia". Ann. Neurol. 52 (5): 643–6. doi:10.1002/ana.10367. PMID   12402263. S2CID   7553866.
• 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. Bibcode:2002PNAS...9916899M. doi: 10.1073/pnas.242603899 . PMC   139241 . PMID   12477932.
• Toone JR, Applegarth DA, Laliberte G (2003). "Gene Symbol: GLDC. Disease: NKH glycine encephalopathy". Hum. Genet. 113 (5): 465. doi:10.1007/s00439-003-1014-5. PMID   14552331. S2CID   266046066.
• Dinopoulos A, Kure S, Chuck G, et al. (2006). "Glycine decarboxylase mutations: a distinctive phenotype of nonketotic hyperglycinemia in adults". Neurology. 64 (7): 1255–7. doi:10.1212/01.WNL.0000156800.23776.40. PMID   15824356. S2CID   38972294.
• Flusser H, Korman SH, Sato K, et al. (2006). "Mild glycine encephalopathy (NKH) in a large kindred due to a silent exonic GLDC splice mutation". Neurology. 64 (8): 1426–30. doi:10.1212/01.WNL.0000158475.12907.D6. PMID   15851735. S2CID   6661158.
• Boneh A, Korman SH, Sato K, et al. (2005). "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. doi: 10.1007/s10038-005-0243-y . PMID   15864413.
• Kimura K, Wakamatsu A, Suzuki Y, et al. (2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes". Genome Res. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC   1356129 . PMID   16344560.
• Korman SH, Wexler ID, Gutman A, et al. (2006). "Treatment from birth of nonketotic hyperglycinemia due to a novel GLDC mutation". Ann. Neurol. 59 (2): 411–5. doi:10.1002/ana.20759. PMID   16404748. S2CID   37119917.