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Information on EC 2.1.1.2 - guanidinoacetate N-methyltransferase and Organism(s) Homo sapiens and UniProt Accession Q14353
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2.1.1.2 guanidinoacetate N-methyltransferaseSpecify your search results
Word Map
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Reaction Schemes
Synonyms
guanidinoacetate methyltransferase, guanidinoacetate n-methyltransferase, guanidoacetate methyltransferase, s-adenosyl-l-methionine:n-guanidinoacetate methyltransferase, n-guanidinoacetate methyltransferase, 
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topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
GA methylpherase
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guanidinoacetate methyltransferase
guanidinoacetate transmethylase
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guanidoacetate methyltransferase
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methionine-guanidinoacetic transmethylase
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guanidinoacetate methyltransferase
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
methyl group transfer
methyl group transfer
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PATHWAY SOURCE
PATHWAYS
BRENDA
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SYSTEMATIC NAME
IUBMB Comments
S-adenosyl-L-methionine:N-guanidinoacetate methyltransferase
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CAS REGISTRY NUMBER
COMMENTARY
9029-75-8
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
S-adenosyl-L-methionine + guanidinoacetate
S-adenosyl-L-homocysteine + creatine
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additional information
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since the L197P mutation in the exon 6 of the guanidinoacetate N-methyltransferase gene leaves the isoform B of the enzyme unaffected, the occurrence of biochemical alterations and disease in this subject testifies against the possibility that isoform B has guanidinoacetate N-methyltransferase activity
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
S-adenosyl-L-methionine + guanidinoacetate
S-adenosyl-L-homocysteine + creatine
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?
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
stable transfection of primary guanidinoacetate N-methyltransferase-deficient fibroblasts with pEGFP-guanidinoacetate N-methyltransferase results in the restoration of guanidinoacetate N-methyltransferase activity to 501 pmol creatine/mg/h from original 1 pmol creatine/mg/h. A 56fold increased guanidinoacetate N-methyltransferase activity is detected in transfected HeLa cells (7700 pmol creatine/mg/h vs. original 137 pmol creatine/mg/h).
additional information
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stable transfection of primary guanidinoacetate N-methyltransferase-deficient fibroblasts with pEGFP-guanidinoacetate N-methyltransferase results in the restoration of guanidinoacetate N-methyltransferase activity to 501 pmol creatine/mg/h from original 1 pmol creatine/mg/h. A 56fold increased guanidinoacetate N-methyltransferase activity is detected in transfected HeLa cells (7700 pmol creatine/mg/h vs. original 137 pmol creatine/mg/h).
additional information
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nonradioactive method for measuring enzyme activity in lymphoblasts by using HPLC with UV detector
additional information
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L197P transition in exon 6 reduces activity to 0.03 nMol creatine/mg/h, activity is assessed in lymphoblasts
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
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L197P mutation in exon 6: guanidinoacetate increases to 33.6 microMol/l, creatine decreases to 24 microMol/l
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L197P mutation in exon 6: guanidinoacetate increases to 2566 microMol/l, creatine decreases to 3.7 microMol/l
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L197P mutation in exon 6, reduces the activity of guanidinoacetate N-methyltransferase
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
guanidinoacetate methyltransferase deficiency, GAMT-D, is an autosomal recessively inherited disorder of creatine biosynthesis. Creatine deficiency on cranial proton magnetic resonance spectroscopy, and elevated guanidinoacetate levels in body fluids are the biomarkers of GAMT-D, 50 different mutations in the GAMT gene have been identified with missense variants being the most common, phenotypes overview
malfunction
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GAMT-deficient patients have strongly decreased levels of creatine in cerebrospinal fluid but are able to import creatine from the blood
physiological function
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GAMT is not only involved in p53-dependent apoptosis in response to genotoxic stress but is important for apoptosis induced by glucose deprivation
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). GAMT_HUMAN
236
0
26318
Swiss-Prot
other Location (Reliability: 2)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
60000
Western Blot analyses shows the presences of the guanidinoacetate N-methyltransferase-EGFP fusion protein
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
A54P
naturally occuring mutation from enzyme deficiency patients, no recombinant expression of the mutant achieved, inactive mutant
A74P
naturally occuring mutation from enzyme deficiency patients, no recombinant expression of the mutant achieved, inactive mutant
C169Y
naturally occuring mutation from enzyme deficiency patients, no recombinant expression of the mutant achieved
D135N
naturally occuring mutation from enzyme deficiency patients, inactive mutant
G68C
naturally occuring mutation from enzyme deficiency patients, no recombinant expression of the mutant achieved
H147Y
naturally occuring mutation from enzyme deficiency patients, almost inactive mutant
H51P
naturally occuring mutation from enzyme deficiency patients, no recombinant expression of the mutant achieved
L166P
naturally occuring mutation from enzyme deficiency patients, inactive mutant
L197P
naturally occuring mutation from enzyme deficiency patients, no recombinant expression of the mutant achieved, inactive mutant
N92D
naturally occuring mutation from enzyme deficiency patients, inactive mutant
P8T
naturally occuring mutation from enzyme deficiency patients, the mutant shows similar activity as the wild-type enzyme
R208P
naturally occuring mutation from enzyme deficiency patients, almost inactive mutant
T136M
naturally occuring mutation from enzyme deficiency patients, inactive mutant
W45R
naturally occuring mutation from enzyme deficiency patients, inactive mutant
Y27H
naturally occuring mutation from enzyme deficiency patients, the mutant shows similar activity as the wild-type enzyme
L197P
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the sequencing of the guanidinoacetate N-methyltransferase gene reveals a homozygous missense mutation on exon 6, resulting in the substitution of leucine in position 197 with proline. The 13-year old girl has mental retardation, as main symptom, associated with a typical pattern of biochemical and neurochemical alterations.
additional information
additional information
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finding of a novel homozygous missense mutation in exon 5, p.Leu166Pro, c.497T>C
additional information
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mutation analysis of the guanidinoacetate methyltransferase gene is performed, the patient is found to be compound heterozygous for a known mitation in exon 2, c.327G>A, and for a novel mutation in exon 1, c170C>A
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
genotyping, overexpression of wild-type and mutant enzymes as EGFP-fusion proteins in a primary enzyme-deficient human fibroblast cell line, homozygous for a frameshift mutation
the open reading frame of the guanidinoacetate N-methyltransferase gene (NM_000156) from a fibroblast cell line is transfected into primary fibroblasts from a guanidinoacetate N-methyltransferase-deficient patient (Trp20Ser) or transient transected in HeLa cells.
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
GAMT induction in response to DNA damage is dependent upon p53, GAMT also shows p53-dependent induction in response to exogenously expressed p53 and genotoxic stress, metabolic stress induces GAMT expression to regulate creatine levels in a p53-dependent manner
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
development of a fast, less invasive, and valid method to measure GAMT activity in lymphocytes using LC-MS/MS. GAMT activity decreases when the venous blood sample is older. Blood isolated after 48 h is not reliable to use for lymphocyte analysis for GAMT enzymatic analysis
analysis
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nonradioactive method for measuring enzyme activity in lymphoblasts by using HPLC with UV detector
medicine
medicine
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guanidinoacetate methyltransferase deficiency is a rare autosomal recessive inborn error of creatine synthesis leading to accumulation of guanidinoacetate and lack of creatine in all tissues, particularly in the brain and muscle
medicine
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guanidinoacetate methyltransferase deficient patients show intellectual disability, epilepsy and sigificant movement disorder
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Grazia Alessandri, M.; Celati, L.; Battini, R.; Baldinotti, F.; Item, C.; Leuzzi, V.; Cioni, G.
HPLC assay for guanidinoacetate methyltransferase
Anal. Biochem.
331
189-191
2004
Homo sapiens
Leuzzi, V.; Carducci, C.; Carducci, C.; Matricardi, M.; Bianchi, M.C.; Di Sabato, M.L.; Artiola, C.; Antonozzi, I.
A mutation on exon 6 of guanidinoacetate methyltransferase (GAMT) gene supports a different function for isoform a and b of GAMT enzyme
Mol. Genet. Metab.
87
88-90
2006
Homo sapiens
Almeida, L.S.; Rosenberg, E.H.; Martinez-Munoz, C.; Verhoeven, N.M.; Vilarinho, L.; Jakobs, C.; Salomons, G.S.
Overexpression of GAMT restores GAMT activity in primary GAMT-deficient fibroblasts
Mol. Genet. Metab.
89
392-394
2006
Homo sapiens (Q14353), Homo sapiens
Vodopiutz, J.; Item, C.B.; Haeusler, M.; Korall, H.; Bodamer, O.A.
Severe speech delay as the presenting symptom of guanidinoacetate methyltransferase deficiency
J. Child Neurol.
22
773-774
2007
Homo sapiens
Braissant, O.; Henry, H.
AGAT, GAMT and SLC6A8 distribution in the central nervous system, in relation to creatine deficiency syndromes: A review
J. Inherit. Metab. Dis.
31
230-239
2008
Homo sapiens, Mus musculus
Verbruggen, K.T.; Sijens, P.E.; Schulze, A.; Lunsing, R.J.; Jakobs, C.; Salomons, G.S.; van Spronsen, F.J.
Successful treatment of a guanidinoacetate methyltransferase deficient patient: findings with relevance to treatment strategy and pathophysiology
Mol. Genet. Metab.
91
294-296
2007
Homo sapiens
Ide, T.; Brown-Endres, L.; Chu, K.; Ongusaha, P.P.; Ohtsuka, T.; El-Deiry, W.S.; Aaronson, S.A.; Lee, S.W.
GAMT, a p53-inducible modulator of apoptosis, is critical for the adaptive response to nutrient stress
Mol. Cell
36
379-392
2009
Homo sapiens, Mus musculus
Mercimek-Mahmutoglu, S.; Ndika, J.; Kanhai, W.; de Villemeur, T.B.; Cheillan, D.; Christensen, E.; Dorison, N.; Hannig, V.; Hendriks, Y.; Hofstede, F.C.; Lion-Francois, L.; Lund, A.M.; Mundy, H.; Pitelet, G.; Raspall-Chaure, M.; Scott-Schwoerer, J.A.; Szakszon, K.; Valayannopoulos, V.; William, M.; Salomons, G.S.
Thirteen new patients with guanidinoacetate methyltransferase deficiency and functional characterization of nineteen novel missense variants in the GAMT gene
Hum. Mutat.
35
462-469
2014
Homo sapiens (Q14353), Homo sapiens
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