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Information on EC 2.1.1.5 - betaine-homocysteine S-methyltransferase and Organism(s) Mus musculus and UniProt Accession O35490
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EC Tree
2.1.1.5 betaine-homocysteine S-methyltransferaseSpecify your search results
Word Map
- 2.1.1.5
- cystathionine
- s-adenosylmethionine
- choline
- folate
-
remethylation
- hyperhomocysteinemia
- s-adenosylhomocysteine
-
adenosyltransferase
- n-methyltransferase
-
one-carbon
- beta-synthase
- dimethylglycine
-
transsulfuration
- methylenetetrahydrofolate
-
5-methyltetrahydrofolate-homocysteine
-
transmethylation
- medicine
- mthfd1
- guanidinoacetate
-
homocysteine-induced
-
folate-dependent
- homocystinuria
- 5-methyltetrahydrofolate
-
transcobalamin
-
b-vitamins
-
slc19a1
- hypotaurine
- molecular biology
- analysis
- nutrition
- food industry
The taxonomic range for the selected organisms is: Mus musculus
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
Synonyms
betaine-homocysteine methyltransferase, betaine-homocysteine s-methyltransferase, betaine homocysteine methyltransferase, bhmt2, betaine:homocysteine methyltransferase, bhmt-2, bhmt1, betaine homocysteine s-methyltransferase, betaine-homocysteine s-methyltransferase 2, betaine:homocysteine s-methyltransferase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
betaine-homocysteine methyltransferase
betaine-homocysteine transmethylase
-
-
-
-
BHMT
methyltransferase, betaine-homocysteine
-
-
-
-
betaine-homocysteine methyltransferase
-
-
-
-
BHMT
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
methyl group transfer
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-
-
-
PATHWAY SOURCE
PATHWAYS
BRENDA
-
-, -, -
SYSTEMATIC NAME
IUBMB Comments
trimethylammonioacetate:L-homocysteine S-methyltransferase
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CAS REGISTRY NUMBER
COMMENTARY
9029-78-1
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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
L-homocysteine + betaine
L-methionine + dimethylglycine
-
-
-
-
?
L-homocysteine + S-methylmethionine
?
-
BHMT-2 uses S-methylmethionine as a methyl donor for the methylation of homocysteine. Unlike BHMT, BHMT-2 can not use betaine
-
-
?
additional information
?
-
-
BHMT can utilize S-methylmethionine as a substrate in vitro with a very low affinity
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-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
S-(delta-Carboxybutyl)-DL-homocysteine
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0.005 mM reduces BHMT activity ca. 95% in the standard assay that contains high levels (0.0025 mM) of L-homocysteine. Compared with saline-injected control mice, at 2 h postinjection, mice have 87% lower BHMT activity and a 2.7fold increase in plasma total homocysteine, effects that last nearly 8 h but return to normal by 24 h, level of BHMT protein remains constant over the 24-h period. After 6 injections (one every 12 h), the mice have 7fold higher plasma total homocysteine, a 65% reduction in the liver S-adenosylmethionine: S-adenosylhomocysteine ratio, and a marked upregulation of BHMT protein expression. When methionine is injected, postmethionine load plasma total homocysteine levels are 2.2fold higher at 2 h postinjection
S-(delta-carboxybutyl)-DL-homocysteine-sulfoxide
-
at 2 h after injection, there is a modest reduction in BHMT activity and a 90% increase in plasma total homocysteine
S-(delta-carboxybutyl)-L-homocysteine
-
at 0.025 mM: 22% inhibition, at 0.0625 mM: 36% inhibition, at 0.125 mM: 49% inhibition, at 0.5 mM: 81% inhibition
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
physiological function
-
in blastocysts, mean inner cell numbers decrease from18-19 in controls to 11-13 when the folate cycle is inhibited by the antifolate methotrexate and to 12-14 when BHMT expression is knocked down by antisense morpholinos. Inhibiting both pathways more severely affects inner cellmass development (7-8 cells).Total SAM levels in mouse blastocysts decrease significantly only when both pathways are inhibited (from 3.1 to 1.6 pmol/100 blastocysts). DNA methylation is minimally affected by inhibition of either pathway alone but decreases by at least 45-55% when both BHMT and the folate cycle are inhibited simultaneously
physiological function
-
high-fat-diet-pretreated mice fed with no-added zinc diet for 4 weeks have the lowest gene and protein expression of betaine homocysteine-S-methyltransferase, cystathionine beta-synthase, and zinc-dependent transcription factor Sp1, compared with control diet or low-fat-diet pretreatment
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). BHMT1_MOUSE
407
0
45021
Swiss-Prot
other Location (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
experiments using the glutamate-cysteine ligase modifier subunit knockout mice Gclm(-/-), which are severely impaired in glutathione synthesis, show that the DMSA-Asp dependent BHMT activity is 75% lower in Gclm(-/-) than Gclm(+/+) mice. The Bet-Hcy dependent BHMT activity is essentially identical between both groups. This results show that the loss of DMSA-Asp dependent activity in Gclm(-/-) is due to the lower level of free thiols in those livers
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
-
transient inhibition of BHMT in vivo causes transient hyperhomocysteinemia
nutrition
-
dietary zinc might be important for the alleviation of oxidative stress and the clearance of homocysteine in high-fat-diet-pretreated mice
additional information
additional information
-
Bhmt expression is strongly regulated by changes in ambient osmolarity, osmotic regulation of BHMT may be part of a cell volume-regulatory response and additionally leads to metabolic alterations that depend on the availability of betaine-derived methyl groups
additional information
-
sequence of the pseudogene BHMT2 shows 97% homology to mouse BHMT
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Schaefer, C.; Hoffmann, L.; Heldt, K.; Lornejad-Schaefer, M.R.; Brauers, G.; Gehrmann, T.; Garrow, T.A.; Haeussinger, D.; Mayatepek, E.; Schwahn, B.C.; Schliess, F.
Osmotic regulation of betaine homocysteine-S-methyltransferase expression in H4IIE rat hepatoma cells
Am. J. Physiol. Gastrointest. Liver Physiol.
292
G1089-G1098
2007
Mus musculus, Rattus norvegicus, Rattus norvegicus (O09171)
Pajares, M.A.; Perez-Sala, D.
Betaine homocysteine S-methyltransferase: just a regulator of homocysteine metabolism?
Cell. Mol. Life Sci.
63
2792-2803
2006
Cavia porcellus, Homo sapiens, Macaca mulatta, Mesocricetus auratus, Mus musculus, Mus musculus C57/BL6J, Ovis aries, Rattus norvegicus, Sus scrofa
Collinsova, M.; Strakova, J.; Jiracek, J.; Garrow, T.A.
Inhibition of betaine-homocysteine S-methyltransferase causes hyperhomocysteinemia in mice
J. Nutr.
136
1493-1497
2006
Mus musculus
Castro, C.; Millian, N.S.; Garrow, T.A.
Liver betaine-homocysteine S-methyltransferase activity undergoes a redox switch at the active site zinc
Arch. Biochem. Biophys.
472
26-33
2008
Homo sapiens, Mus musculus
Szegedi, S.S.; Castro, C.C.; Koutmos, M.; Garrow, T.A.
Betaine-homocysteine S-methyltransferase-2 is an S-methylmethionine-homocysteine methyltransferase
J. Biol. Chem.
283
8939-8945
2008
Homo sapiens, Mus musculus
Liu, H.H.; Lu, P.; Guo, Y.; Farrell, E.; Zhang, X.; Zheng, M.; Bosano, B.; Zhang, Z.; Allard, J.; Liao, G.; Fu, S.; Chen, J.; Dolim, K.; Kuroda, A.; Usuka, J.; Cheng, J.; Tao, W.; Welch, K.; Liu, Y.; Pease, J.; de Keczer, S.A.; Masjedizadeh, M.; Hu, J.S.; Weller, P.; Garrow, T.; Peltz, G.
An integrative genomic analysis identifies Bhmt2 as a diet-dependent genetic factor protecting against acetaminophen-induced liver toxicity
Genome Res.
20
28-35
2010
Mus musculus
Lee, M.B.; Kooistra, M.; Zhang, B.; Slow, S.; Fortier, A.L.; Garrow, T.A.; Lever, M.; Trasler, J.M.; Baltz, J.M.
Betaine homocysteine methyltransferase is active in the mouse blastocyst and promotes inner cell mass development
J. Biol. Chem.
287
33094-33103
2012
Mus musculus (O35490), Mus musculus
Zhang, B.; Denomme, M.M.; White, C.R.; Leung, K.Y.; Lee, M.B.; Greene, N.D.; Mann, M.R.; Trasler, J.M.; Baltz, J.M.
Both the folate cycle and betaine-homocysteine methyltransferase contribute methyl groups for DNA methylation in mouse blastocysts
FASEB J.
29
1069-1079
2015
Mus musculus
Wu, L.; Zhou, X.; Li, T.; He, J.; Huang, L.; Ouyang, Z.; He, L.; Wei, T.; He, Q.
Improved Sp1 and betaine homocysteine-S-methyltransferase expression and homocysteine clearance are involved in the effects of zinc on oxidative stress in high-fat-diet-pretreated mice
Biol. Trace Elem. Res.
184
436-441
2018
Mus musculus
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