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Information on EC 1.4.4.2 - glycine dehydrogenase (aminomethyl-transferring) and Organism(s) Homo sapiens

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IUBMB Comments
A pyridoxal-phosphate protein. A component of the glycine cleavage system, which is composed of four components that only loosely associate: the P protein (EC 1.4.4.2), the T protein (EC 2.1.2.10, aminomethyltransferase), the L protein (EC 1.8.1.4, dihydrolipoyl dehydrogenase) and the lipoyl-bearing H protein . Previously known as glycine synthase.
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Homo sapiens
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Word Map
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
Synonyms
gdc, h protein, h-protein, glycine decarboxylase, t protein, protein p1, h1 protein, glycine decarboxylase complex, glycine cleavage enzyme complex, h2 protein, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
decarboxylase, glycine
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glycine cleavage enzyme complex
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Glycine cleavage system P-protein
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glycine decarboxylase
glycine decarboxylase P-protein
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glycine dehydrogenase
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glycine dehydrogenase (decarboxylating)
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glycine-cleavage complex
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H-protein
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P protein
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P-protein
P-protein (glycine decarboxylase)
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Protein P1
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REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
glycine + [glycine-cleavage complex H protein]-N6-lipoyl-L-lysine = [glycine-cleavage complex H protein]-S-aminomethyl-N6-dihydrolipoyl-L-lysine + CO2
show the reaction diagram
mechanism of the GLDC-catalyzed reaction, detailed overview. GLDC is an unusual PLP-containing alpha-amino acid decarboxylase that removes carbon dioxide from the glycine substrate without releasing the expected amine (methylamine, a metabolic precursor of toxic formaldehyde) as a product. In an unusual decarboxylation mechanism, the resulting aminomethyl moiety is instead transferred to an accessory H-protein. (1) H-Protein is not required for glycine decarboxylation but, instead, is required for the release of the aminomethyl moiety from the quinonoid adduct. (2) Glycine decarboxylation is reversible and presumably proceeds through a stable quinonoid intermediate. (3) The physiological product of glycine decarboxylation is H-protein-S-aminomethyl dihydrolipoyllysine and not methylamine (in the absence of H-protein, the aminomethyl moiety remains as a quinonoid adduct)
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
decarboxylation
oxidation
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redox reaction
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reduction
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SYSTEMATIC NAME
IUBMB Comments
glycine:H-protein-lipoyllysine oxidoreductase (decarboxylating, acceptor-amino-methylating)
A pyridoxal-phosphate protein. A component of the glycine cleavage system, which is composed of four components that only loosely associate: the P protein (EC 1.4.4.2), the T protein (EC 2.1.2.10, aminomethyltransferase), the L protein (EC 1.8.1.4, dihydrolipoyl dehydrogenase) and the lipoyl-bearing H protein [3]. Previously known as glycine synthase.
CAS REGISTRY NUMBER
COMMENTARY hide
37259-67-9
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SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
glycine + H-protein-lipoyllysine
H-protein-S-aminomethyldihydrolipoyllysine + CO2
show the reaction diagram
glycine + [glycine-cleavage complex H protein]-N6-lipoyl-L-lysine
[glycine-cleavage complex H protein]-S-aminomethyl-N6-dihydrolipoyl-L-lysine + CO2
show the reaction diagram
additional information
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
glycine + H-protein-lipoyllysine
H-protein-S-aminomethyldihydrolipoyllysine + CO2
show the reaction diagram
glycine + [glycine-cleavage complex H protein]-N6-lipoyl-L-lysine
[glycine-cleavage complex H protein]-S-aminomethyl-N6-dihydrolipoyl-L-lysine + CO2
show the reaction diagram
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r
additional information
?
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nonketotic hyperglycinaemia is an autosomal recessive disorder of glycine metabolism caused by a deficiency in the mitochondrial glycine cleavage enzyme. The majority of cases are caused by mutations in the P-protein
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
pyridoxal 5'-phosphate
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Mg2+
required
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
H-protein
upon addition of exogenous unlipoylated H-protein, kcat increases 190fold, in the absence of the lipoic acid moiety on H-protein, the methylamine adduct with pyridoxal 5'-phosphate (aminomethyl-quinonoid intermediate) is released as the product of the GLDC-catalyzed decarboxylation of glycine
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lipoylated H-protein
the presence of the lipoyl moiety on H-protein does not affect the rates of GLDC (or GLDCcoexp)-catalyzed glycine decarboxylation
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additional information
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0003 - 2.1
glycine
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0001 - 0.047
glycine
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.009 - 890
glycine
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
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mutations have a 6 to 8% of normal glycine decarboxylase activities when expressed in COS7 cells
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
25
assay at
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
inhibition of the enzyme induces alterations of metabolome and advanced glycation end product (AGEs) accumulation, thereby suppressing the embryonic pluripotent state. Glycine decarboxylase-mediated regulation of glycolysis and controlling AGE accumulation is related to maintenance and induction of pluripotency
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
glycine decarboxylase is a key enzyme of glycine cleavage system that converts glycine into one-carbon units
physiological function
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
GCSP_HUMAN
1020
0
112730
Swiss-Prot
Mitochondrion (Reliability: 3)
Q9HDA3_HUMAN
331
0
36549
TrEMBL
other Location (Reliability: 2)
A0A1W2PQV3_HUMAN
388
0
42610
TrEMBL
Mitochondrion (Reliability: 5)
A0A1J0GNC2_HUMAN
914
0
101395
TrEMBL
other Location (Reliability: 1)
A0A1W2PP74_HUMAN
420
0
46273
TrEMBL
Mitochondrion (Reliability: 5)
A0A1W2PPH6_HUMAN
140
0
15840
TrEMBL
Mitochondrion (Reliability: 4)
GCSH_HUMAN
173
0
18885
Swiss-Prot
Secretory Pathway (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
200000
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value about
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
homodimer
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monomer
1 * 112730, mass spectrometry
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
acetylation
the activity is regulated by sequential posttranslational modifications, including acetylation and polyubiquitination, and reveal critical regulatory mechanisms of glycine metabolism and tumorigenesis. Acetylation of K514 inhibits glycine catabolism and pyrimidine synthesis. In addition, this acetylation of glycine decarboxylase also primes for its K33-linked polyubiquitination and proteasomal degradation, leading to suppression of glycine metabolism and tumorigenesis
ubiquitination
the activity is regulated by sequential posttranslational modifications, including acetylation and polyubiquitination (K33-linked polyubiquitination), and reveal critical regulatory mechanisms of glycine metabolism and tumorigenesis
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
A389V
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missense mutation, 6-8% of normal GLDC activity when expressed in COS7 cells
R739H
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missense mutation, 6-8% of normal GLDC activity when expressed in COS7 cells
R998Q
homozygous mutation within the GLDC gene is detected in a neonate with the neonatal type of nonketotic hyperglycinemia
additional information
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
Ni-NTA column chromatography
recombinant His6-tagged enzymes from Escherichia coli strain BL21(DE3) by nickel affinity chromatography and dialysis
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in Pichia pastoris strain GS115
gene GLDC, DNA and amino acid sequence determination and analysis, genotyping
missense mutations expressed in COS7 cells
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recombinant expression of codon optimized C-terminally His6-tagged enzyme GLDC in Escherichia coli strain BL21(DE3), GLDC is expressed either separately (without H-protein) or simultaneously with H-protein, coexpression of His6-tagged enzyme with codon-optimized human H-protein in Escherichia coli strain BL21(DE3) from pJexpress-416 vector
two identified mutations, A389V and R739V, are introduced into the pEUK-(N) expression vector pEUK-(C1) carrying human glycine decarboxylase complementary DNA for expression in COS7 cells
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
glycine decarboxylase (GLDC) is a direct transcriptional target of MYCN. As a result, GLDC expression is markedly elevated in neuroblastoma tumors and cell lines amplified by the oncogene
glycine decarboxylase is commonly up-regulated and plays important roles in many human cancers
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
diagnostics
medicine
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Toone, J.R.; Applegarth, D.A.; Kure, S.; Coulter-Mackie, M.B.; Sazegar, P.; Kojima, K.; Ichinohe, A.
Novel mutations in the P-protein (glycine decarboxylase) gene in patients with glycine encephalopathy (non-ketotic hyperglycinemia)
Mol. Genet. Metab.
76
243-249
2002
Homo sapiens
Manually annotated by BRENDA team
Sellner, L.; Edkins, E.; Greed, L.; Lewis, B.
Detection of mutations in the glycine decarboxylase gene in patients with nonketotic hyperglycinaemia
Mol. Genet. Metab.
84
167-171
2005
Homo sapiens
Manually annotated by BRENDA team
Dinopoulos, A.; Kure, S.; Chuck, G.; Sato, K.; Gilbert, D.L.; Matsubara, Y.; Degrauw, T.
Glycine decarboxylase mutations: a distinctive phenotype of nonketotic hyperglycinemia in adults
Neurology
64
1255-1257
2005
Homo sapiens
Manually annotated by BRENDA team
Kikuchi, G.; Motokawa, Y.; Yoshida, T.; Hiraga, K.
Glycine cleavage system: reaction mechanism, physiological significance, and hyperglycinemia
Proc. Jpn. Acad. Ser. B Phys. Biol. Sci.
84
246-263
2008
Gallus gallus, Gottschalkia acidurici, Escherichia coli, Peptoclostridium acidaminophilum, Thermus thermophilus, Homo sapiens, Pisum sativum
Manually annotated by BRENDA team
Zay, A.; Choy, F.Y.; Patrick, C.; Sinclair, G.
Glycine cleavage enzyme complex: molecular cloning and expression of the H-protein cDNA from cultured human skin fibroblasts
Biochem. Cell Biol.
89
299-307
2011
Homo sapiens (P23434), Homo sapiens
Manually annotated by BRENDA team
Go, M.K.; Zhang, W.C.; Lim, B.; Yew, W.S.
Glycine decarboxylase is an unusual amino acid decarboxylase involved in tumorigenesis
Biochemistry
53
947-956
2014
Homo sapiens (P23378), Homo sapiens
Manually annotated by BRENDA team
Azize, N.A.; Ngah, W.Z.; Othman, Z.; Md Desa, N.; Chin, C.B.; Md Yunus, Z.; Mohan, A.; Hean, T.S.; Syed Zakaria, S.Z.; Lock-Hock, N.
Mutation analysis of glycine decarboxylase, aminomethyltransferase and glycine cleavage system protein-H genes in 13 unrelated families with glycine encephalopathy
J. Hum. Genet.
59
593-597
2014
Homo sapiens (P23378), Homo sapiens
Manually annotated by BRENDA team
Wei, H.Y.; Feng, R.; Shao, H.; Feng, B.; Liu, H.Q.; Men, J.L.; Zou, W.
Serum glycine dehydrogenase is associated with increased risk of lung cancer and promotes malignant transformation by regulating DNA methyltransferases expression
Mol. Med. Rep.
18
2293-2299
2018
Homo sapiens (P23378)
Manually annotated by BRENDA team
Zhuang, H.; Li, Q.; Zhang, X.; Ma, X.; Wang, Z.; Liu, Y.; Yi, X.; Chen, R.; Han, F.; Zhang, N.; Li, Y.
Downregulation of glycine decarboxylase enhanced cofilin-mediated migration in hepatocellular carcinoma cells
Free Radic. Biol. Med.
120
1-12
2018
Homo sapiens (P23378)
Manually annotated by BRENDA team
Kang, P.J.; Zheng, J.; Lee, G.; Son, D.; Kim, I.Y.; Song, G.; Park, G.; You, S.
Glycine decarboxylase regulates the maintenance and induction of pluripotency via metabolic control
Metab. Eng.
53
35-47
2019
Homo sapiens (P23378)
Manually annotated by BRENDA team
Liu, R.; Zeng, L.W.; Gong, R.; Yuan, F.; Shu, H.B.; Li, S.
mTORC1 activity regulates post-translational modifications of glycine decarboxylase to modulate glycine metabolism and tumorigenesis
Nat. Commun.
12
4227
2021
Homo sapiens (P23378), Homo sapiens
Manually annotated by BRENDA team
Kose, E.; Yis, U.; Hiz, S.; Arslan, N.
A novel mutation in the glycine decarboxylase gene in patient with non-ketotic hyperglycinemia
Neurosciences (Riyadh)
22
131-133
2017
Homo sapiens (P23378), Homo sapiens
Manually annotated by BRENDA team
Alptekin, A.; Ye, B.; Yu, Y.; Poole, C.J.; van Riggelen, J.; Zha, Y.; Ding, H.F.
Glycine decarboxylase is a transcriptional target of MYCN required for neuroblastoma cell proliferation and tumorigenicity
Oncogene
38
7504-7520
2019
Homo sapiens (P23378)
Manually annotated by BRENDA team
Berezowska, S.; Galvan, J.A.; Langer, R.; Bubendorf, L.; Savic, S.; Gugger, M.; Schmid, R.A.; Marti, T.M.
Glycine decarboxylase and HIF-1alpha expression are negative prognostic factors in primary resected early-stage non-small cell lung cancer
Virchows Arch.
470
323-330
2017
Homo sapiens (P23378), Homo sapiens
Manually annotated by BRENDA team