Any feedback?
No. of entries
Information on EC 2.1.1.5 - betaine-homocysteine S-methyltransferase
for references in articles please use BRENDA:EC2.1.1.5
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree 2 Transferases
2.1 Transferring one-carbon groups
2.1.1 Methyltransferases
2.1.1.5 betaine-homocysteine S-methyltransferase
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
- 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
showSynonyms
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
topPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
betaine homocysteine methyltransferase
betaine homocysteine S-methyltransferase
betaine-homocysteine methyltransferase
betaine-homocysteine S-methyltransferase
betaine-homocysteine S-methyltransferase-2
betaine-homocysteine transmethylase
-
-
-
-
BHMT
BHMT2
methyltransferase, betaine-homocysteine
-
-
-
-
betaine-homocysteine methyltransferase
-
-
-
-
BHMT
-
-
-
-
BHMT
-
-
BHMT
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
betaine + L-homocysteine = dimethylglycine + L-methionine
ordered bi-bi mechanism with homocysteine the first substrate to be added and methionine the last product released
-
betaine + L-homocysteine = dimethylglycine + L-methionine
-
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
methyl group transfer
-
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
PATHWAY SOURCE
PATHWAYS
BRENDA
MetaCyc
glycine betaine degradation I, glycine betaine degradation II (mammalian), L-methionine salvage from L-homocysteine
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SYSTEMATIC NAME
IUBMB Comments
trimethylammonioacetate:L-homocysteine S-methyltransferase
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
CAS REGISTRY NUMBER
COMMENTARY
9029-78-1
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
betaine + DL-homocysteine
dimethylglycine + L-methionine
-
Substrates: -
Products: -
Products: -
r
dimethylacetothetin + L-homocysteine
? + L-methionine
Substrates: -
Products: -
Products: -
?
glycinebetaine + L-homocysteine
? + L-methionine
-
Substrates: -
Products: -
Products: -
?
L-homocysteine + S-methyl-L-methionine
2 L-methionine
Substrates: -
Products: -
Products: -
?
L-homocysteine + S-methylmethionine
2 L-methionine
-
Substrates: -
Products: -
Products: -
?
L-homocysteine + S-methylmethionine
?
-
Substrates: BHMT-2 uses S-methylmethionine as a methyl donor for the methylation of homocysteine. Unlike BHMT, BHMT-2 can not use betaine
Products: -
Products: -
?
additional information
?
-
-
Substrates: BHMT can utilize S-methylmethionine as a substrate in vitro with a very low affinity
Products: -
Products: -
?
betaine + L-homocysteine
dimethylglycine + L-methionine
Substrates: -
Products: -
Products: -
?
betaine + L-homocysteine
dimethylglycine + L-methionine
Substrates: -
Products: -
Products: -
?
betaine + L-homocysteine
dimethylglycine + L-methionine
-
Substrates: -
Products: -
Products: -
?
L-Asp + dimethylsulfonioacetate
?
-
Substrates: using the non-physiological methyl donor dimethylsulfonioacetate an O-methylation of Asp is performed by BHMT, but only in the presence of beta-mercaptoethanol
Products: -
Products: -
?
L-homocysteine + betaine
dimethylglycine + L-methionine
Substrates: -
Products: -
Products: -
?
L-homocysteine + betaine
dimethylglycine + L-methionine
Substrates: -
Products: -
Products: -
?
L-homocysteine + betaine
dimethylglycine + L-methionine
-
Substrates: -
Products: -
Products: -
?
L-homocysteine + betaine
L-methionine + dimethylglycine
-
Substrates: -
Products: -
Products: -
?
L-homocysteine + betaine
L-methionine + dimethylglycine
-
Substrates: -
Products: -
Products: -
?
L-homocysteine + betaine
L-methionine + dimethylglycine
Substrates: -
Products: -
Products: -
?
L-homocysteine + betaine
L-methionine + dimethylglycine
-
Substrates: -
Products: -
Products: -
?
L-homocysteine + betaine
L-methionine + dimethylglycine
-
Substrates: reduced BHMT activity in cirrhotic livers may explain the elevated plasma homocysteine levels in cirrhosis
Products: -
Products: -
?
L-homocysteine + betaine
L-methionine + dimethylglycine
Substrates: -
Products: -
Products: -
?
L-homocysteine + betaine
L-methionine + dimethylglycine
-
Substrates: -
Products: -
Products: -
?
L-homocysteine + betaine
L-methionine + dimethylglycine
Substrates: -
Products: -
Products: -
?
L-homocysteine + betaine
L-methionine + dimethylglycine
-
Substrates: folate-independent remethylation of homocysteine
Products: -
Products: -
?
L-homocysteine + betaine
L-methionine + dimethylglycine
-
Substrates: this reaction processes 25% of the cellular L-homocysteine in an in vitro model
Products: -
Products: -
?
L-homocysteine + betaine
L-methionine + dimethylglycine
-
Substrates: -
Products: -
Products: -
?
L-homocysteine + betaine
L-methionine + dimethylglycine
-
Substrates: the enzyme can be modified by tissue-type transglutaminase and its activity is regulated repressively by the modification, especially by the cross-linking. This regulatory reaction might be involved in the regulation of homocysteine metabolism in the liver
Products: -
Products: -
?
L-homocysteine + betaine
L-methionine + dimethylglycine
-
Substrates: -
Products: -
Products: -
?
L-homocysteine + betaine
L-methionine + dimethylglycine
Substrates: -
Products: -
Products: -
?
L-homocysteine + S-methyl-L-methionine
?
-
Substrates: BHMT-2 uses S-methylmethionine as a methyl donor for the methylation of homocysteine. Unlike BHMT, BHMT-2 can not use betaine
Products: -
Products: -
?
N,N,N-trimethylglycine + L-homocysteine
N,N-dimethylglycine + L-methionine
-
Substrates: -
Products: -
Products: -
?
N,N,N-trimethylglycine + L-homocysteine
N,N-dimethylglycine + L-methionine
-
Substrates: -
Products: -
Products: -
?
N,N,N-trimethylglycine + L-homocysteine
N,N-dimethylglycine + L-methionine
-
Substrates: i.e. betaine, methyl transfer directly from one substrate to the other
Products: -
Products: -
?
N,N,N-trimethylglycine + L-homocysteine
N,N-dimethylglycine + L-methionine
-
Substrates: enzyme cristallin in lens
Products: -
Products: -
?
N,N,N-trimethylglycine + L-homocysteine
N,N-dimethylglycine + L-methionine
-
Substrates: -
Products: -
Products: -
?
N,N,N-trimethylglycine + L-homocysteine
N,N-dimethylglycine + L-methionine
-
Substrates: i.e. betaine, involved in betaine metabolism
Products: -
Products: -
?
N,N,N-trimethylglycine + L-homocysteine
N,N-dimethylglycine + L-methionine
-
Substrates: -
Products: -
Products: -
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
betaine + L-homocysteine
dimethylglycine + L-methionine
Substrates: -
Products: -
Products: -
?
betaine + L-homocysteine
dimethylglycine + L-methionine
Substrates: -
Products: -
Products: -
?
betaine + L-homocysteine
dimethylglycine + L-methionine
-
Substrates: -
Products: -
Products: -
?
L-homocysteine + betaine
L-methionine + dimethylglycine
-
Substrates: reduced BHMT activity in cirrhotic livers may explain the elevated plasma homocysteine levels in cirrhosis
Products: -
Products: -
?
L-homocysteine + betaine
L-methionine + dimethylglycine
-
Substrates: the enzyme can be modified by tissue-type transglutaminase and its activity is regulated repressively by the modification, especially by the cross-linking. This regulatory reaction might be involved in the regulation of homocysteine metabolism in the liver
Products: -
Products: -
?
N,N,N-trimethylglycine + L-homocysteine
N,N-dimethylglycine + L-methionine
-
Substrates: enzyme cristallin in lens
Products: -
Products: -
?
N,N,N-trimethylglycine + L-homocysteine
N,N-dimethylglycine + L-methionine
-
Substrates: i.e. betaine, involved in betaine metabolism
Products: -
Products: -
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
K+
Km value around 0.1 mM. The presence of potassium ions lowers the apparent KM of the enzyme for homocysteine, but it does not affect the apparent KM for betaine or the apparent kcat for either substrate
Zinc
wild-type enzyme contains zinc. Mutant enzymes H338A, R346A, W352A, R361A, P362A, Y363A, N364A, P365A maintain normal or near-normal ability to bind zinc
Zn
Zn2+
Zn2+
-
wild-type enzyme contains catalytic active zinc which is bound by three thiolates and one hydroxyl group. Long-term exposure of BHMT to reducing agent-free buffer results in the slow, irreversible loss of its catalytic Zn and a corresponding loss of activity
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(2S,11RS)-5-thia-2,11-diamino-8,8-dimethyldodecanedioic acid
-
more than 90% inhibition at 0.02 mM
(2S,11RS)-5-thia-2,11-diaminododecanedioic acid
-
about 60% inhibition at 0.02 mM
(2S,11S)-5,8-dithia-2,11-diaminododecanedioic acid
-
about 60% inhibition at 0.02 mM
(2S,5RS,8RS,11S)-5,8-dithia-2,11-diaminododecanedioic acid 5,8-dioxide
-
about 20% inhibition at 0.02 mM
(2S,8RS,11RS)-5-thia-2,11-diamino-8-methyldodecanedioic acid
-
competitive, more than 90% inhibition at 0.02 mM
(R,S)-2-(3-amino-3-carboxy-propylsulfanyl)-benzoic acid
-
ca. 43% inhibition at 0.02 mM
(R,S)-2-amino-4-(2-carboxy-ethyldisulfanyl)-butyric acid
-
ca. 30% inhibition at 0.02 mM
(R,S)-2-amino-4-(2-carboxymethylsulfanyl-ethylsulfanyl)-butyric acid
-
100% inhibition at 0.02 mM, very potent inhibitor and one of the strongest ever reported
(R,S)-2-amino-4-(2-carboxymethylsulfinyl-ethylsulfanyl)-butyric acid
-
ca. 90% inhibition at 0.02 mM
(R,S)-2-amino-4-(2-phosphonomethoxy-ethylsulfanyl)-butyrate
-
ca. 26% inhibition at 0.02 mM
(R,S)-2-amino-4-(3-carboxy-propylsulfanyl)-butyric acid
-
ca. 20% inhibition at 0.02 mM
(R,S)-2-amino-4-(4-carboxymethyl-benzylsulfanyl)-butyric acid
-
ca. 10% inhibition at 0.02 mM
(R,S)-2-amino-4-(4-phosphono-butylsulfanyl)-butyric acid
-
ca. 98% inhibition at 0.02 mM
(R,S)-2-amino-4-methylsulfanylmethylsulfanyl-butyric acid
-
ca. 21% inhibition at 0.02 mM
(R,S)-2-amino-4-[(phosphonomethyl-carbamoyl)-methylsulfanyl]-butyrate
-
ca. 9% inhibition at 0.02 mM
(R,S)-3-(3-amino-3-carboxy-propylsulfanyl)-benzoic acid
-
ca. 13% inhibition at 0.02 mM
(R,S)-4-(3-amino-3-carboxy-propylsulfanyl)-benzoic acid
-
ca. 99% inhibition at 0.02 mM
(R,S)-5-(3-amino-3-carboxy-propylsulfanyl)-pentanoic acid
-
100% inhibition at 0.02 mM, very potent inhibitor and one of the strongest ever reported, competitive inhibition with respect to betaine binding
(R,S)-5-(3-amino-3-carboxy-propylsulfinyl)-pentanoic acid
-
ca. 97% inhibition at 0.02 mM
(R,S)-5-(3-amino-3-carboxy-propylsulfonyl)-pentanoic acid
-
ca. 29% inhibition at 0.02 mM
(R,S)-6-(3-amino-3-carboxy-propylsulfanyl)-hexanoic acid
-
100% inhibition at 0.02 mM, very potent inhibitor and one of the strongest ever reported
(R,S,R,S)-2-amino-4-(2-amino-2-carboxy-ethylsulfinyl)-butyric acid
-
ca. 10% inhibition at 0.02 mM
(RS)-2-amino-4-[(2-carboxyethylthio)methylthio]butanoic acid
-
97.6% inhibition at 0.02 mM
(RS)-2-amino-4-[(3-carboxypropyl)disulfanyl]butanoic acid
-
19.1% inhibition at 0.02 mM
(RS)-2-amino-4-[2-(carboxymethylamino)ethylthio]butanoic acid
-
37.1% inhibition at 0.02 mM
(RS)-2-amino-4-[2-(R)-(1-carboxyethylamino)ethylthio]butanoic acid
-
15.5% inhibition at 0.02 mM
(RS)-2-amino-4-[2-(S)-(1-carboxyethylamino)ethylthio]butanoic acid
-
19.8% inhibition at 0.02 mM
(RS)-2-amino-4-[2-[(carboxymethyl)(methyl)amino]ethylthio]-butanoic acid
-
98.5% inhibition at 0.02 mM
(RS)-2-amino-4-[3-[(carboxymethyl)(methyl)amino]propylthio]butanoic acid
-
79.01% inhibition at 0.02 mM
(RS)-2-[[2-(3-amino-3-carboxypropylthio)ethyl]dimethylammonium]acetate
-
23.8% inhibition at 0.02 mM
(RS)-2-[[3-(3-amino-3-carboxypropylthio)propyl]dimethylammonio]acetate
-
3.3% inhibition at 0.02 mM
(RS)-5-(3-amino-3-carboxypropylselanyl)pentanoic acid
-
complete inhibition at 0.02 mM
(RS)-5-(3-amino-3-carboxypropylthio)-3,3-dimethylpentanoic acid
-
highly potent inhibitor of BHMT, complete inhibition at 0.02 mM
(RS)-5-(3-amino-3-carboxypropylthio)-3-methylpentanoic acid
-
highly potent inhibitor of BHMT, complete inhibition at 0.02 mM
5-[(3-amino-3-carboxypropyl)sulfanyl]pentanoic acid
-
complete inhibition at 0.02 mM
5-[3-(R,S)-3-amino-3-(hydroxyphosphorylpropyl)sulfanyl]-3,3-dimethylpentanoic acid
-
actinomycin D
leads to a decay of Bhmt mRNA, irrespective of the ambient osmolarity, at 120 min after addition, Bhmt mRNA levels are significantly decreased under hyperosmotic conditions, compared with the Bhmt mRNA levels found under the respective normo- or hypoosmotic condition
H2O2
causes a loss of catalytic Zn and a correlative loss of activity, irreversible
methyl methanethiosulfonate
causes a loss of catalytic Zn and a correlative loss of activity. Addition of beta-mercaptoethanol and exogenous Zn after methyl methanethiosulfonate treatment restores activity
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-adenosyl-L-ethionine
-
irreversible, S-adenosyl-L-homocysteine and L-homocysteine prevent, but not DL-homocysteine, GSH, DTT or L-cysteine
S-adenosyl-L-homocysteine
-
non-linear/competitive to homocysteine, mixed/non-competitive to betaine
dimethylglycine
-
at 0.2 mM: 80% inhibition, at 2 mM: 97% inhibition; weak inhibitor, at 2 mM: 11% inhibition
dimethylglycine
-
at 0.25 mM: 64% inhibition, at 2.5 mM: 95% inhibition; weak inhibitor, at 2.5 mM: 19% inhibition
dimethylsulfonioacetate
-
at 2 mM: 79% inhibition; weak inhibitor, at 2 mM: 20% inhibition
dimethylsulfoniopropionate
-
weak inhibitor, at 2.5 mM: 11% inhibition; weak inhibitor, at 2.5 mM: 17% inhibition
S-(delta-Carboxybutyl)-DL-homocysteine
-
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)-L-homocysteine
-
at 0.05 mM: 97% inhibition, at 0.5 mM: total inhibition; weak inhibitor, at 0.5 mM: 26% inhibition
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; total inhibition
S-adenosyl-L-methionine
-
irreversible, S-adenosyl-L-homocysteine and L-homocysteine prevent, not DL-homocysteine, GSH, DTT or L-cysteine
additional information
-
hypertonicity induces a decrease in BHMT mRNA and protein levels in liver and kidney
-
additional information
-
not inhibitory: methionine or ethionine; product inhibition
-
additional information
-
no inhibition by sarcosine; not inhibitory: S-(gamma-carboxypropyl)-DL-homocysteine, S-(beta-carboxyethyl)-DL-homocysteine
-
additional information
-
no inhibition by Ac-Val-DL-Ala-psi[(PO2-)-CH2]-DL-Leu-Cys-NH2, Ac-DL-Ala-psi[(PO2-)-CH2]-DL-Leu-NH2, Ac-Val-DL-Ala-psi[(PO2-)-CH2]-DL-Leu-His
-
additional information
S-adenosylmethionine decreases BHMT mRNA levels in dose- and time-dependent manner, down-regulates BHMT expression in part by inducing nuclear factor kappaB, which acts as a repressor for the human BHMT gene, the inhibitor is nuclear factor kappaB dependent. 5'-methylthioadenosine decreases BHMT mRNA levels in dose- and time-dependent manner, down-regulates BHMT expression in part by inducing nuclear factor kappaB, which acts as a repressor for the human BHMT gene, the inhibitor has nuclear factor kappaB dependent and -independent mechanisms
-
additional information
-
S-adenosylmethionine decreases BHMT mRNA levels in dose- and time-dependent manner, down-regulates BHMT expression in part by inducing nuclear factor kappaB, which acts as a repressor for the human BHMT gene, the inhibitor is nuclear factor kappaB dependent. 5'-methylthioadenosine decreases BHMT mRNA levels in dose- and time-dependent manner, down-regulates BHMT expression in part by inducing nuclear factor kappaB, which acts as a repressor for the human BHMT gene, the inhibitor has nuclear factor kappaB dependent and -independent mechanisms
-
additional information
-
not inhibited by (R)-5-(2-amino-2-carboxy-ethylsulfanyl)-pentanoic acid, (R,S)-4-allylsulfanyl-2-amino-butyric acid and (R,S)-2-amino-4-[(phosphonomethyl-carbamoyl)-methylsulfanyl]-butyric acid ester
-
additional information
-
not inhibited by (RS)-2-[[(3-amino-3-carboxypropylthio)methyl]dimethylammonium] acetate and (RS)-2-amino-4-[2-(2-carboxyethylamino)ethylthio]butanoic acid
-
additional information
-
not inhibitory: taurine, cysteic acid, cysteine sulfinate, sulfate, glycine, L-serine, L-threonine; product inhibition
-
additional information
-
insulin decreases the abundance of BHMT mRNA and the rate of de novo mRNA transcription of the gene in H4IIE cells, plays a direct role in the regulation of BHMT transcription
-
additional information
-
hyperosmotic NaCl, hyperosmotic raffinose but not hyperosmotic urea suppresses Bhmt mRNA expression, suggesting that cell shrinkage rather than increased ionic strength or hyperosmolarity per se is the trigger, osmosensitivity of Bhmt mRNA expression is impaired by inhibitors of tyrosine kinases and cyclic nucleotide-dependent kinases
-
additional information
hyperosmotic NaCl, hyperosmotic raffinose but not hyperosmotic urea suppresses Bhmt mRNA expression, suggesting that cell shrinkage rather than increased ionic strength or hyperosmolarity per se is the trigger, osmosensitivity of Bhmt mRNA expression is impaired by inhibitors of tyrosine kinases and cyclic nucleotide-dependent kinases
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
beta-mercaptoethanol
-
using a redox-inert methyl acceptor, it is shown that BHMT requires a thiol reducing agent for activity. Short-term exposure of BHMT to reducing agent-free buffer inactivates the enzyme without causing any loss of its catalytic zinc. Activity can be completely restored by the re-addition of a thiol reducing agent
Insulin
-
is effective in counteracting the stimulation of BHMT activity and mRNA levels produced by triamcinolone in rat hepatoma H4IIE cells
-
L-methionine
-
independent of dietary choline, supplemental methionine increases hepatic BHMT activity by ca. 30%
betaine
-
only slightly increased homocysteine remethylation in response to addition of betaine to diets containing 0.07 and 0.24% supplemental methionine
betaine
-
together with methionine restriction induces hepatic BHMT 4fold compared with methionine restriction alone, BHMT mRNAlevel is also increased by 3fold by betaine supplementation of methionine-replete diets
choline
-
liver BHMT activity is 1.3fold higher in rats fed the methionine deficient diet containing choline than in rats fed the methionine-adequate diet containing supplemental choline
choline
-
elevations in the liver activity, whereas it has no effect in the renal enzyme
ethanol
-
increases in BHMT activity are only observed when 4-methylpyrazole is included in the treatment
additional information
-
dietary methionine level does not significantly affect BHMT-dependent homocysteine remethylation or the relative proportion of homocysteine that is remethylated by BHMT, also choline appears to have little impact on BHMT-dependent remethylation
-
additional information
-
taurine, cysteic acid, cysteine sulfinate, sulfate, glycine, L-serine, L-threonine do not affect activity
-
additional information
-
triamcinolone increases the level and rate of BHMT mRNA synthesis in H4IIE cells
-
additional information
-
choline and methionine do not affect BHMT activity, mRNA expression and immunodetectable protein in the kidney
-
additional information
-
after 24 h, Bhmt expression increases 1.53fold under hypoosmotic conditions, Bhmt enzymatic activity is altered under anisoosmotic conditions
-
additional information
after 24 h, Bhmt expression increases 1.53fold under hypoosmotic conditions, Bhmt enzymatic activity is altered under anisoosmotic conditions
-
additional information
-
diet increases BHMT activity with small elevations in expression
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Abruptio Placentae
Polymorphisms in methionine synthase reductase and betaine-homocysteine S-methyltransferase genes: risk of placental abruption.
Adenoma
Twenty-four non-synonymous polymorphisms in the one-carbon metabolic pathway and risk of colorectal adenoma in the Nurses' Health Study.
Anencephaly
Neural tube defects and folate pathway genes: family-based association tests of gene-gene and gene-environment interactions.
Atherosclerosis
Betaine:homocysteine methyltransferase--a new assay for the liver enzyme and its absence from human skin fibroblasts and peripheral blood lymphocytes.
betaine-homocysteine s-methyltransferase deficiency
Betaine-homocysteine S-methyltransferase deficiency causes increased susceptibility to noise-induced hearing loss associated to plasma hyperhomocysteinemia.
betaine-homocysteine s-methyltransferase deficiency
Homocysteinemia in mice with genetic betaine homocysteine S-methyltransferase deficiency is independent of dietary folate intake.
betaine-homocysteine s-methyltransferase deficiency
Mouse betaine-homocysteine S-Methyltransferase deficiency reduces body fat via increasing energy expenditure and impairing lipid synthesis and enhancing glucose oxidation in white adipose tissue.
Breast Neoplasms
Dietary choline and betaine intake, choline-metabolising genetic polymorphisms and breast cancer risk: a case-control study in China.
Carcinoma
L-arginine-glycine amidinotransferase, betaine-homocysteine S-methyltransferase, and neuropolypeptide H3 are diminished in renal clear cell carcinoma of humans.
Carcinoma, Hepatocellular
A splicing variant leads to complete loss of function of betaine-homocysteine methyltransferase (BHMT) gene in hepatocellular carcinoma.
Carcinoma, Hepatocellular
Deletion of betaine-homocysteine S-methyltransferase in mice perturbs choline and 1-carbon metabolism, resulting in fatty liver and hepatocellular carcinomas.
Carcinoma, Hepatocellular
Downregulation of betaine homocysteine methyltransferase (BHMT) in hepatocellular carcinoma associates with poor prognosis.
Carcinoma, Hepatocellular
Osmotic regulation of betaine homocysteine-S-methyltransferase expression in H4IIE rat hepatoma cells.
Carcinoma, Hepatocellular
Reduced mRNA abundance of the main enzymes involved in methionine metabolism in human liver cirrhosis and hepatocellular carcinoma.
Cardiovascular Diseases
Betaine homocysteine S-methyltransferase: just a regulator of homocysteine metabolism?
Cardiovascular Diseases
The betaine/GABA transporter and betaine: roles in brain, kidney, and liver.
Choline Deficiency
Common genetic polymorphisms affect the human requirement for the nutrient choline.
Cleft Lip
Are the betaine-homocysteine methyltransferase (BHMT and BHMT2) genes risk factors for spina bifida and orofacial clefts?
Cleft Lip
New evidence for the role of cystathionine beta-synthase in non-syndromic cleft lip with or without cleft palate.
Cleft Palate
Are the betaine-homocysteine methyltransferase (BHMT and BHMT2) genes risk factors for spina bifida and orofacial clefts?
Cleft Palate
New evidence for the role of cystathionine beta-synthase in non-syndromic cleft lip with or without cleft palate.
Coronary Artery Disease
Investigations of a common genetic variant in betaine-homocysteine methyltransferase (BHMT) in coronary artery disease.
cystathionine beta-synthase deficiency
Mice deficient in cystathionine beta synthase display altered homocysteine remethylation pathway.
Diabetes Mellitus
Betaine ameliorates impaired steroidogenesis and apoptosis in mice granulosa cells induced by high glucose concentration.
Down Syndrome
Betaine-homocysteine methyltransferase 742G>A polymorphism and risk of down syndrome offspring in a Brazilian population.
Endometriosis
Polymorphic variants of folate and choline metabolism genes and the risk of endometriosis-associated infertility.
Fatty Liver
Choline deprivation induces hyperhomocysteinemia in rats fed low methionine diets.
Fatty Liver
Deletion of betaine-homocysteine S-methyltransferase in mice perturbs choline and 1-carbon metabolism, resulting in fatty liver and hepatocellular carcinomas.
Fatty Liver
Effect of transgenic extrahepatic expression of betaine-homocysteine methyltransferase on alcohol or homocysteine-induced fatty liver.
Hearing Loss, Noise-Induced
Betaine-homocysteine S-methyltransferase deficiency causes increased susceptibility to noise-induced hearing loss associated to plasma hyperhomocysteinemia.
Homocystinuria
Mice deficient in cystathionine beta synthase display altered homocysteine remethylation pathway.
Homocystinuria
Taurine alleviates repression of betaine-homocysteine S-methyltransferase and significantly improves the efficacy of long-term betaine treatment in a mouse model of cystathionine ?-synthase-deficient homocystinuria.
Hyperhomocysteinemia
Betaine-homocysteine methyltransferase (BHMT): genomic sequencing and relevance to hyperhomocysteinemia and vascular disease in humans.
Hyperhomocysteinemia
Betaine-homocysteine S-methyltransferase deficiency causes increased susceptibility to noise-induced hearing loss associated to plasma hyperhomocysteinemia.
Hyperhomocysteinemia
Dietary Egg Protein Prevents Hyperhomocysteinemia via Upregulation of Hepatic Betaine-Homocysteine S-Methyltransferase Activity in Folate-Restricted Rats.
Hyperhomocysteinemia
Effects of betaine supplementation and choline deficiency on folate deficiency-induced hyperhomocysteinemia in rats.
Hyperhomocysteinemia
Effects of hyperhomocysteinemia and betaine-homocysteine S-methyltransferase inhibition on hepatocyte metabolites and the proteome.
Hyperhomocysteinemia
Exercise prevents hyperhomocysteinemia in a dietary folate-restricted mouse model.
Hyperhomocysteinemia
Hyperhomocysteinemia in polycystic ovary syndrome: decreased betaine-homocysteine methyltransferase and cystathionine ?-synthase-mediated homocysteine metabolism.
Hyperhomocysteinemia
Inhibition of betaine-homocysteine S-methyltransferase causes hyperhomocysteinemia in mice.
Hyperhomocysteinemia
Inhibition of betaine-homocysteine S-methyltransferase in rats causes hyperhomocysteinemia and reduces liver cystathionine ?-synthase activity and methylation capacity.
Hyperhomocysteinemia
Suppression effects of betaine-enriched spinach on hyperhomocysteinemia induced by guanidinoacetic acid and choline deficiency in rats.
Hyperhomocysteinemia
Triiodothyronine treatment attenuates the induction of hepatic glycine N-methyltransferase by retinoic acid and elevates plasma homocysteine concentrations in rats.
Hyperthyroidism
The impact of B vitamins on the functioning of methylation cycle in the liver and the kidneys of hyper- and hypothyroid rats.
Hypothyroidism
SULPHUR-CONTAINING AMINO ACIDS METABOLISM IN EXPERIMENTAL HYPER- AND HYPOTHYROIDISM IN RATS.
Hypothyroidism
The impact of B vitamins on the functioning of methylation cycle in the liver and the kidneys of hyper- and hypothyroid rats.
Insulin Resistance
Extra Virgin Olive Oils Increase Hepatic Fat Accumulation and Hepatic Antioxidant Protein Levels in APOE(-/-)() Mice.
Insulin Resistance
The Heme Oxygenase System Selectively Modulates Proteins Implicated in Metabolism, Oxidative Stress and Inflammation in Spontaneously Hypertensive Rats.
Ischemic Stroke
Early-onset ischaemic stroke: analysis of 58 polymorphisms in 17 genes involved in methionine metabolism.
Liver Cirrhosis
Betaine homocysteine methyltransferase: gene cloning and expression analysis in rat liver cirrhosis.
Lung Injury
Alleviation of paraquat-induced oxidative lung injury by betaine via regulation of sulfur-containing amino acid metabolism despite the lack of betaine-homocysteine methyltransferase (BHMT) in the lung.
Lymphoma, B-Cell
Betaine ameliorates impaired steroidogenesis and apoptosis in mice granulosa cells induced by high glucose concentration.
Meningomyelocele
Neural tube defects and folate pathway genes: family-based association tests of gene-gene and gene-environment interactions.
Neoplasms
A splicing variant leads to complete loss of function of betaine-homocysteine methyltransferase (BHMT) gene in hepatocellular carcinoma.
Neoplasms
Betaine ameliorates impaired steroidogenesis and apoptosis in mice granulosa cells induced by high glucose concentration.
Neoplasms
Down-regulation of metabolic proteins in hepatocellular carcinoma with portal vein thrombosis.
Neoplasms
Proteomic differences between hepatocellular carcinoma and non-tumorous liver tissue investigated by a combined 2D-DIGE and label-free quantitative proteomics study.
Obesity
Are genetic variants of the methyl group metabolism enzymes risk factors predisposing to obesity?
Polycystic Ovary Syndrome
Hyperhomocysteinemia in polycystic ovary syndrome: decreased betaine-homocysteine methyltransferase and cystathionine ?-synthase-mediated homocysteine metabolism.
Spinal Dysraphism
Are the betaine-homocysteine methyltransferase (BHMT and BHMT2) genes risk factors for spina bifida and orofacial clefts?
Spinal Dysraphism
Common variant in betaine-homocysteine methyltransferase (BHMT) and risk for spina bifida.
Starvation
Degradation of glycinebetaine by betaine-homocysteine methyltransferase in Aphanothece halophytica: effect of salt downshock and starvation.
Stroke
Early-onset ischaemic stroke: analysis of 58 polymorphisms in 17 genes involved in methionine metabolism.
Thrombosis
Betaine:homocysteine methyltransferase--a new assay for the liver enzyme and its absence from human skin fibroblasts and peripheral blood lymphocytes.
Thrombosis
Down-regulation of metabolic proteins in hepatocellular carcinoma with portal vein thrombosis.
Vascular Diseases
Betaine-homocysteine methyltransferase (BHMT): genomic sequencing and relevance to hyperhomocysteinemia and vascular disease in humans.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2.3
L-homocysteine
wild-type, cosubstrate S-methylmethionine, presence of 150 mM KCl, pH 7.5, 37°C
3.4
S-methyl-L-methionine
wild-type, presence of 150 mM KCl, pH 7.5, 37°C
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0003
L-homocysteine
wild-type, cosubstrate S-methylmethionine, presence of 150 mM KCl, pH 7.5, 37°C
0.0044
S-methyl-L-methionine
wild-type, presence of 150 mM KCl, pH 7.5, 37°C
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000077
(2S,8RS,11RS)-5-thia-2,11-diamino-8-methyldodecanedioic acid
-
IC50 for betaine-homocysteine S-methyltransferase about 0.077 mM, pH 7.5, 37°C
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000096
(R,S)-2-amino-4-(2-carboxymethylsulfanyl-ethylsulfanyl)-butyric acid
Homo sapiens
-
-
0.00326
(RS)-2-amino-4-[(2-carboxyethylthio)methylthio]butanoic acid
Homo sapiens
-
in 50 mM potassium phosphate buffer, at pH 7.5, at 37°C
0.0025
(RS)-2-amino-4-[2-[(carboxymethyl)(methyl)amino]ethylthio]-butanoic acid
Homo sapiens
-
in 50 mM potassium phosphate buffer, at pH 7.5, at 37°C
0.000649
(RS)-5-(3-amino-3-carboxypropylselanyl)pentanoic acid
Homo sapiens
-
in 50 mM potassium phosphate buffer, at pH 7.5, at 37°C
0.000084
(RS)-5-(3-amino-3-carboxypropylthio)-3,3-dimethylpentanoic acid
Homo sapiens
-
in 50 mM potassium phosphate buffer, at pH 7.5, at 37°C
0.000139
(RS)-5-(3-amino-3-carboxypropylthio)-3-methylpentanoic acid
Homo sapiens
-
in 50 mM potassium phosphate buffer, at pH 7.5, at 37°C
0.000093
5-(3-amino-3-carboxy-propylsulfanyl)-pentanoic acid
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
0.0011
5-[3-(R,S)-3-amino-3-(hydroxyphosphorylpropyl)sulfanyl]-3,3-dimethylpentanoic acid
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.4
7.5
additional information
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
BHMT expression is observed in the amygdala of basal ganglia and the cerebral cortex where BHMT levels are clearly elevated during torpor
brenda
BHMT expression is observed in the amygdala of basal ganglia and the cerebral cortex where BHMT levels are clearly elevated during torpor
brenda
-
low BHMT activity is detected in the G30 fetus, and slightly increased levels of activity are observed in the liver from G45 and G90 fetuses
brenda
hyperosmolarity (405 mosmol/l) suppresses Bhmt mRNA expression whereas hypoosmotic (205 mosmol/l) conditions induce Bhmt mRNA expression. Like hyperosmotic NaCl, hyperosmotic raffinose but not hyperosmotic urea suppresses Bhmt mRNA expression. Osmosensitivity of Bhmt mRNA expression is impaired by inhibitors of tyrosine kinases and cyclic nucleotide-dependent kinases
brenda
additional information
-
high sodium chloride intake decreases betaine-homocysteine S-methyltransferase expression
brenda
-
transcripts are expressed at significant levels in the liver and kidney from day 45 of gestation onward
brenda
-
represents 0.5-10% of the total protein, presence of BHMT can be related to its role in betaine removal when osmotic stress disappears, a key process, since osmotic swelling is a major factor in the development of some types of cataracts
brenda
-
compared with the prepartum level, overall BHMT expression and enzyme activity increases 0.7-fold and 1.7-fold, respectively, soon after parturition. There is no overall effect of methionine or choline supplementation for BHMT expression or BHMT enzyme activity
brenda
-
reduced BHMT activity in cirrhotic livers may explain the elevated plasma homocysteine levels in cirrhosis
brenda
-
BHMT mRNA and activity increases about 2fold in diabetic rats compared with the nondiabetic animals
brenda
-
high sodium chloride intake decreases betaine-homocysteine S-methyltransferase expression
brenda
-
transcripts are expressed at significant levels in the liver and kidney from day 45 of gestation onward
brenda
-
high sodium chloride intake has no effect on betaine-homocysteine S-methyltransferase expression
brenda
additional information
-
no activity in phytohemagglutinin-stimulated human peripheral blood lymphocytes and cultured human skin fibroblasts
brenda
additional information
-
no expression of BHMT2 protein is detected in liver or kidney although BHMT2 mRNA expression is observed
brenda
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
Highest Expressing Human Cell Lines
Cell Line LinksPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
physiological function
-
betaine homocysteine methyltransferase is a potential cargo-based end-point marker for macroautophagy
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
in hybernating bats, homocysteine level does not elevate in brains, despite declining vitamin B levels. At low levels of vitamin B6 and B12, no change in total expression level of methionine synthase and cystathionine beta-synthase is found, but a 1.85fold increase in the expression of the coenzyme-independent betaine-homocysteine S-methyltransferase
physiological function
-
in rats fed methionine and choline-deficient diet, betaine supplementation reverses the reduction of methionine and S-adenosylmethionine, and the elevation of homocysteine levels in the liver, due to the induction of betaine-homocysteine methyltransferase and methionine adenosyltransferase MAT
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
physiological function
identification of interactions of betaine homocysteine S-methyltransferase in normal liver. S-methylmethionine homocysteine methyltransferase or betaine homocysteine methyltransferase 2, methionine adenosyltransferases alpha1 and alpha2, cAMP-dependent protein kinase catalytic subunit alpha, 4-hydroxyphenylpyruvic acid dioxygenase and aldolase b. Network analysis identified 122 nodes and 165 edges, as well as a limited number of KEGG pathways that comprise the biosynthesis of amino acids, cysteine and methionine metabolism, the spliceosome and metabolic pathways
physiological function
enzyme expression leads to increased NADPH production and subsequent upregulation of fat mass and obesity-associated protein expression
physiological function
enzyme overexpression promotes adipocyte commitment and differentiation in vitro and exacerbates adipose tissue expansion in vivo, with a concomitant increase in insulin resistance. The enzyme promotes adipogenic lineage commitment through p38 MAPK/Smad signaling
physiological function
enzyme overexpression promotes adipocyte commitment and differentiation in vitro and exacerbates adipose tissue expansion in vivo, with a concomitant increase in insulin resistance. The enzyme promotes adipogenic lineage commitment through p38 MAPK/Smad signaling
physiological function
betaine acts through the enzyme to modulate histone and DNA methyltransferase activity on chromatin
physiological function
-
betaine acts through the enzyme to modulate histone and DNA methyltransferase activity on chromatin
Show AA Sequence and Transmembrane Helices (278 entries)
Please use the AA Sequence and Transmembrane Helices Search for a specific query.
Please use the AA Sequence and Transmembrane Helices Search for a specific query.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
PDB
SCOP
CATH
UNIPROT
ORGANISM
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
270000
40300
45000
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hexamer
tetramer
tetramer
wild-type enzyme and mutant enzymes E266A, H338A, R346A, R361A, P362A, N364A and P365A
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
the enzyme can be modified by tissue-type transglutaminase and its activity is regulated repressively by the modification, especially by the cross-linking. This regulatory reaction might be involved in the regulation of homocysteine metabolism in the liver
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
molecular dynamics simulations predict that K+ ions interact with residues Asp26 and/or Glu159. Crystal structure of BHMT bound to homocysteine confirms these sites of interaction and reveals further contacts between K+ ions and BHMT residues Gly27, Gln72, Gln247, and Gly298
crystals with P2(1) symmetry, assymetric unit contains the whole functional tetramer showing point symmetry 222
dominant structural feature of wild type BHMT is an (betaalpha)8 barrel. A modeled structure of truncated BHMT suggests that this protein would assume a horseshoe fold and lack methyltransferase activity
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
A66V
-
nonsynonymous SNP identified using 240 DNA samples from four ethnic groups
Arg16Cys
-
nonsynonymous SNP identified using 240 DNA samples from four ethnic groups, Km (mM): 0.0139 (betaine), 0.0076 (L-homocysteine)
Arg239Gln
-
nonsynonymous SNP identified using 240 DNA samples from four ethnic groups, Km (mM): 0.012 (betaine), 0.0158 (L-homocysteine)
C104A
-
site-directed mutagenesis is used to investigate whether the loss of the DMSA-Asp activity of BHMT when in the absence of a reducing agent is due to the oxidation of an essential thiol within the protein. By individual mutation of each of the five Cys residues not involved in Zn binding to Ala, it is shown that the resulting mutants are as active as wild-type enzyme when in the presence of beta-mercaptoethanol with the DMSA-Asp assay
C131A
-
site-directed mutagenesis is used to investigate whether the loss of the DMSA-Asp activity of BHMT when in the absence of a reducing agent is due to the oxidation of an essential thiol within the protein. By individual mutation of each of the five Cys residues not involved in Zn binding to Ala, it is shown that the resulting mutants are as active as wild-type enzyme when in the presence of beta-mercaptoethanol with the DMSA-Asp assay
C186A
-
site-directed mutagenesis is used to investigate whether the loss of the DMSA-Asp activity of BHMT when in the absence of a reducing agent is due to the oxidation of an essential thiol within the protein. By individual mutation of each of the five Cys residues not involved in Zn binding to Ala, it is shown that the resulting mutants are as active as wild-type enzyme when in the presence of beta-mercaptoethanol with the DMSA-Asp assay
C201A
-
site-directed mutagenesis is used to investigate whether the loss of the DMSA-Asp activity of BHMT when in the absence of a reducing agent is due to the oxidation of an essential thiol within the protein. By individual mutation of each of the five Cys residues not involved in Zn binding to Ala, it is shown that the resulting mutants are as active as wild-type enzyme when in the presence of beta-mercaptoethanol with the DMSA-Asp assay
C217A
-
the mutation reduces zinc binding by 95% while abrogating catalytic activity, the mutation has no effect on the fold increase of GST-BHMT proteolytic fragment in the absence of nutrients
C256A
-
site-directed mutagenesis is used to investigate whether the loss of the DMSA-Asp activity of BHMT when in the absence of a reducing agent is due to the oxidation of an essential thiol within the protein. By individual mutation of each of the five Cys residues not involved in Zn binding to Ala, it is shown that the resulting mutants are as active as wild-type enzyme when in the presence of beta-mercaptoethanol with the DMSA-Asp assay
Cys217Ala
-
complete loss of activity, reduction in zinc binding, identification of zinc binding motif
Cys299Ala
-
complete loss of activity, reduction in zinc binding, identification of zinc binding motif
Cys300Ala
-
complete loss of activity, reduction in zinc binding, identification of zinc binding motif
DELTA325-406
truncation mutatnt does not express well in Escherichia coli and is inactive
DELTA371-406
truncation mutant does not express well in Escherichia coli and is inactive
G742A
-
in an ongoing, multicenter, case-control study including women with a clinical diagnosis of abruption an association between the homozygous mutant form of BHMT (742G to A) polymorphism and an increased risk for placental abruption is shown
Gly199Ser
-
nonsynonymous SNP identified using 240 DNA samples from four ethnic groups, Km (mM): 0.0139 (betaine), 0.0206 (L-homocysteine)
H338A
normal or near-normal ability to bind zinc, 10% of the wild-type activity
N364A
normal or near-normal ability to bind zinc, near-normal catalytic activity
P362A
normal or near-normal ability to bind zinc, near-normal catalytic activity
P365A
normal or near-normal ability to bind zinc, near-normal catalytic activity
Pro197Ser
-
nonsynonymous SNP identified using 240 DNA samples from four ethnic groups, Km (mM): 0.0213 (betaine), 0.0216 (L-homocysteine)
R239Q
-
no significant association with the severity and extent of hyperhomocysteinemia
R346A
normal or near-normal ability to bind zinc, negligible activity, elution as dimer, aberrant crosslinking properties
R361A
normal or near-normal ability to bind zinc, near-normal catalytic activity
T218M
-
nonsynonymous SNP identified using 240 DNA samples from four ethnic groups
V155F
-
nonsynonymous SNP identified using 240 DNA samples from four ethnic groups
V237M
-
nonsynonymous SNP identified using 240 DNA samples from four ethnic groups
W352A
Y363A
normal or near-normal ability to bind zinc, near-normal catalytic activity
A119G
1.9fold reduced turnover-number for betaine and L-homocysteine, 1.6fold reduced KM-value for L-homocysteine, 1.1fold decrease in Km-value for betaine
C186A
1.8fold reduced turnover-number for betaine and L-homocysteine, 4.3fold reduced KM-value for L-homocysteine, 1.8fold increase in Km-value for betaine
C186S
2.3fold reduced turnover-number for betaine and L-homocysteine, 1.4fold reduced KM-value for L-homocysteine, 111.6fold decrease in Km-value for betaine
D26A
2.7fold reduced turnover-number for betaine and L-homocysteine, 1.7fold reduced KM-value for L-homocysteine, 3.5fold increase in Km-value for betaine
D26I
67fold reduced turnover-number for betaine and L-homocysteine, maximal velocity is 6.5fold lower than the wild-type value
E159G
60fold reduced turnover-number for betaine and L-homocysteine, maximal velocity is 61.2fold lower than the wild-type value
E159K
170fold reduced turnover-number for betaine and L-homocysteine, maximal velocity is 169.7fold lower than the wild-type value
E21A
2.3fold reduced turnover-number for betaine and L-homocysteine, 6fold reduced KM-value for L-homocysteine, 2.4fold reduced Km-value for betaine
E21K
1.6fold reduced turnover-number for betaine and L-homocysteine, 1.4fold reduced KM-value for L-homocysteine, 1.7fold reduced Km-value for betaine
F74A
1.9fold reduced turnover-number for betaine and L-homocysteine, 1.9fold reduced KM-value for L-homocysteine, 2.9fold increase in Km-value for betaine
T184G
2.4fold reduced turnover-number for betaine and L-homocysteine, 3.19fold reduced KM-value for L-homocysteine, 1.6fold increase in Km-value for betaine
T73G
3.1fold reduced turnover-number for betaine and L-homocysteine, 2.2fold reduced KM-value for L-homocysteine, 1.3fold reduced Km-value for betaine
Y77A
14fold reduced turnover-number for betaine and L-homocysteine, maximal velocity is 13.7fold lower than the wild-type value
additional information
W352A
negligible activity, elution as dimer, aberrant crosslinking properties
W352A
-
the mutation disrupts stable BHMT multimerization, the mutant ablates catalytic activity
additional information
-
random mutagenesis of zinc binding motif, Gly214 is essential
additional information
deletion mutants ranging from -2698 to +33, construct -347/+33 has maximal promoter activity, inhibition in promoter activity by S-adenosylmethionine or 5'-methylthioadenosine most pronounced within this construct, cycloleucine treatment increases the reporter activity driven by the BHMT promoter construct -347/+33 but does not block the ability of 5'-methylthioadenosine to inhibit the BHMT promoter activity and blocks the conversion of 5'-methylthioadenosine into S-adenosylmethionine
additional information
-
deletion mutants ranging from -2698 to +33, construct -347/+33 has maximal promoter activity, inhibition in promoter activity by S-adenosylmethionine or 5'-methylthioadenosine most pronounced within this construct, cycloleucine treatment increases the reporter activity driven by the BHMT promoter construct -347/+33 but does not block the ability of 5'-methylthioadenosine to inhibit the BHMT promoter activity and blocks the conversion of 5'-methylthioadenosine into S-adenosylmethionine
additional information
S-adenosylmethionine and 5-methylthioadenosine treatment of HepG2 cells result in a dose- and time-dependent decrease in BHMT mRNA levels, which parallels their effects on the BHMT promoter activity. Maximal suppression is observed with BHMT promoter construct -347/+33, containing a number of NF-kappaB binding sites. S-adenosylmethionine and 5-methylthioadenosine treatment increases NF-kappaB nuclear binding and NF-kappaB-driven luciferasece activities, and increases nuclear binding activity of multiple histone deacetylase co-repressors to the NF-kappaB sites. Overexpression of p50 and p65 decreases BHMT promoter activity, while blocking NF-kappaB activation increases BHMT expression and promoter activity, and prevents S-adenosylmethionine but not 5-methylthioadenosines ability to inhibit BHMT expression
additional information
-
S-adenosylmethionine and 5-methylthioadenosine treatment of HepG2 cells result in a dose- and time-dependent decrease in BHMT mRNA levels, which parallels their effects on the BHMT promoter activity. Maximal suppression is observed with BHMT promoter construct -347/+33, containing a number of NF-kappaB binding sites. S-adenosylmethionine and 5-methylthioadenosine treatment increases NF-kappaB nuclear binding and NF-kappaB-driven luciferasece activities, and increases nuclear binding activity of multiple histone deacetylase co-repressors to the NF-kappaB sites. Overexpression of p50 and p65 decreases BHMT promoter activity, while blocking NF-kappaB activation increases BHMT expression and promoter activity, and prevents S-adenosylmethionine but not 5-methylthioadenosines ability to inhibit BHMT expression
additional information
-
betaine-homocysteine methyltransferase transgenic (Tg) mice are generated. BHMT transgenic mice are resistant to alcohol or high methionine low folate diet-induced hyperhomocysteinemia and liver steatosis indicating that peripheral metabolism of homocysteine protects the liver without a direct effect of BHMT in the liver
additional information
both BHMT transfectants of HepG2 cells and primary mouse hepatocytes with suppressed BHMT are generated. Expression of BHMT in HepG2 cells ameliorates the homocysteine metabolism and inhibits homocysteine-induced glucose-regulated protein 78 (GRP78) and C/EBP-homologous protein (CHOP) and homocysteine-induced cell death. A betaine treatment protects primary mouse hepatocytes from a homocysteine-induced increase in GRP78 and cell death. Homocysteine induces greater CHOP expression (2.7fold) in BHMT small interfering RNA -transfected cells than in a control (1.9fold). Homocysteine-induced cell death is increased by 40% in the siRNA-treated cells in comparison with the control. Apolipoprotein B (apoB) expression is higher and triglycerides and cholesterol is lower in HepG2 expressing BHMT. In primary mouse hepatocytes, homocysteine induces the accumulation of triglycerides and cholesterol, which is reduced in the presence of betaine
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
additional information
-
changes at positions E159 and Y77 show the largest decreases in activity, but D26 and F74 seem to have a role in betaine binding, whereas E21 and C186 also influence L-homocysteine binding
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
divalent cations and 2-mercaptoethanol do not stabilize during purification
-
mechanism of unfolding by urea includes two intermediate states, a tetramer and a monomer. Dissociation is concomitant with alterations in the dimerization arm and the loop connecting the C-terminal helix, and intermediate conformations originate from perturbations in these structures
-
partial digestion of ligand-free enzyme with trypsin produces two large peptides, excising a seven residue peptide with loop L2. Carboxybutylhomocysteine but not methionine slows proteolysis by trypsin
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
OXIDATION STABILITY
ORGANISM
UNIPROT
LITERATURE
the enzyme is susceptible to conformation-dependent oxidative inactivation. When BHMT is incubated with up to 78 mM t-butyl hydroperoxide, no appreciable amount of ZN or activity is lost, indicating that oxidation of surface met residues are not involved in the oxidative inactivation of BHMT. Methyl methanethiosulfonate and H2O2, cause a loss of catalytic Zn and a correlative loss of activity. Addition of beta-mercaptoethanol and exogenous Zn after methyl methanethiosulfonate treatment restores activity, but oxidation due to H2O2 is irreversible. The L2 loop is involved in the conformational change associated with accupancy at the betaine binding site. This conformational change and/or occupancy at both ligand binding sites protects the enzyme from oxidative inactivation
657875
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
stable for a minimum of one month at 4°C in a mixture with human recombinant betaine-homocysteine S-methyltransferase (copurified with human recombinant betaine-homocysteine S-methyltransferase)
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
stabilized by copurification with human recombinant betaine-homocysteine S-methyltransferase, chitin affinity chromatography
-
wild-type and mutant enzymes are overexpressed in Escherichia coli and purified using the ImpactTM T7 system
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
a 2.7 kb 5'-flanking region of the human BHMT gene cloned between MluI and SmaI sites of a promoterless pGL-3-basic vector creating the recombinant plasmid -2698/+33 BHMT-LUC, expression in HepG2 cells
expressed in Escherichia coli BL21(DE3) (coexpression of human recombinant betaine-homocysteine S-methyltransferase)
-
glutathione S-transferase-BHMT fusion protein is expressed in HEK-293, T98G, A-10, MCF-7, H-1299, C2C12, and NIH-3T3 cells
-
impossible to express BHMT2 in mammalian cells, protein aggregates after bacterial expression. BHMT2 is rapidly degraded in a rabbit reticulocyte lysate, but it can be stabilized by cotransfection of COS-1 cells with BHMT and, after cotransfection, it coprecipitates with BHMT
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
corticosteroids stimulate activity in the liver and also up-regulate the gene expression
-
during fetal development, a total of ten splice variants of BHMT are expressed at varying levels across a wide range of porcine tissues. Two variants contain an identical ORF that encodes a C-terminal truncated form of BHMT
-
significant upregulation of betaine homocysteine methyltransferase-1 in livers of rats fed a betaine supplemented ethanol diet
-
the activity of hepatic BHMT significantly increases with increase in both dietary casein level and dietary methionine level, hepatic level of mRNA for BHMT is parallel to the enzyme activity
-
the enzyme expression is increased 2fold following oxidative insult
the enzyme expression is increased in obesity
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
-
synthesis of a series of S-substituted derivatives of homocysteine as potential inhibitors of human recombinant BHMT, some of these compounds are very potent inhibitors, having IC50 values in the nanomolar range
food industry
-
compared with the prepartum level, overall BHMT expression and enzyme activity increases 0.7-fold and 1.7-fold, respectively, soon after parturition. There is no overall effect of methionine or choline supplementation for BHMT expression or BHMT enzyme activity
medicine
molecular biology
nutrition
additional information
medicine
-
methionine-deficient diet produces large increase in enzyme activity
medicine
-
decreased plasma homocysteine in various models of diabetes may be due to enhanced homocysteine removal brought about by a combination of increased transsulfuration of homocysteine to cysteine and increased remethylation of homocysteine to methionine by BHMT
medicine
-
transient inhibition of BHMT in vivo causes transient hyperhomocysteinemia
medicine
-
upregulation of BHMT may indicate an increased choline requirement in the diabetic rat
medicine
-
Zucker diabetic fatty rats show increased BHMT activity and mRNA levels
medicine
-
effect of extrahepatic expression of homo sapiens betaine-homocysteine methyltransferase on alcohol or homocysteine-induced fatty liver is shown in transgenic mice
medicine
-
a polymorphisms in betaine-homocysteine S-methyltransferase might be linked to an increased risk for placental abruption
medicine
treatment of hepatocytes with homocysteine to follow the impact of hyperhomocysteinemia and concomittant inhibition of betaine-homocysteine S-methyltransferase BHMT. Inhibition and 0.1 mM homocysteine treatment induce only moderate changes in the hepatocyte proteome and secretome, while the changes induced by 2 mM homocysteine treatment are extensive: phosphatidylethanolamine carboxykinase and ornithine aminotransferase are up-regulated about twofold indicating an intervention into metabolism. Cellular proliferation is suspended, secretome composition is changed and signs of apoptosis are discernible. Fibrinogen gamma dimers can be detected and maturation of apolipoprotein A1 fails
medicine
-
in serum from healthy individuals, the median value is 1.83 ng/ml. In serum from patients with acute liver injury, the median value of BHMT is 748.48 ng/ml. The detection range of the ELISA assay is from 1.56 to 100 ng/ml with good sensitivity and specificity. In five acute liver injury cases with time course samples available, BHMT and alanine transaminase both follow the rise and fall temporal pattern with the disease progression. The slopes of BHMT curves are steeper than alanine transaminase curves. In three out of the five cases, BHMT levels peak 1 day earlier than alanine transaminase levels
medicine
-
BHMT1 is a auto-antigen associated with anti-Golgi immune reactivity. Antibodies to BHMT1 were found in four of 80 samples with a Golgi-pattern on indirect immunofluorescence. The antibodies are not associated with a specific clinical condition
medicine
the enzyme is a therapeutic target for obesity and obesity-related diabetes
medicine
the enzyme is a therapeutic target for obesity and obesity-related diabetes
molecular biology
S-adenosylmethionine and 5-methylthioadenosine down-regulate BHMT expression in HepG2 cells in part by inducing NF-kappaB, which acts as a repressor for the human BHMT gene. While S-adenosylmethionines mechanism is NF-kappaB-dependent, 5-methylthioadenosine has both NF-kappaB-dependent and -independent mechanisms
molecular biology
osmotic regulation of BHMT may be part of a cell volume-regulatory response and additionally lead to metabolic alterations that depend on the availability of betaine-derived methyl groups
molecular biology
the BHMT/betaine system directly protects hepatocytes from homocysteine-induced injury but not tunicamycin-induced injury, including an endoplasmic reticulum stress response, lipid accumulation, and cell death
nutrition
-
dietary zinc might be important for the alleviation of oxidative stress and the clearance of homocysteine in high-fat-diet-pretreated mice
nutrition
-
rats fed a casein-based diet lacking folate exhibit a 53% increase in circulating homocysteine concentrations compared with rats fed a casein-based diet including folate. Serum homocysteine does not differ between rats fed casein-based diet including folate and egg protein-based diet lacking folate. Hepatic BHMT activity is increased by 45% and 40% by the egg protein-based diet and whole egg-based diet compared with the casein-based diets, respectively
nutrition
-
activity and mRNA abundance of hepatic BHMT are greater with restricted water intake and increase with choline supplementation. Enhanced supply of choline during negative energy balance increases hepatic activity of BHMT and MTR to regenerate methionine and phosphatidylcholine, partly to help clear triacylglycerols
additional information
lower BHMT expression can impair homocysteine metabolism, which can induce endoplasmic reticulum stress
additional information
-
lower BHMT expression can impair homocysteine metabolism, which can induce endoplasmic reticulum stress
additional information
-
in contrast to previous suppositions based on enzyme activity, under most dietary conditions, the quantity of homocysteine remethylated by methionine synthase appeared to exceed that remethylated by the alternate betaine-homocysteine methyltransferase pathway
additional information
-
relationship between BHMT expression and ApoB mRNA in transfected McA cells recapitulated in vivo through dietary BHMT induction, providing additional support for a physiologic linkage between 1-carbon metabolism and apob gene expression
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
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
-
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
additional information
-
sequence of the pseudogene BHMT2 shows 97% homology to mouse BHMT
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Wang, J.; Dudman, N.P.; Lynch, J.; Wilcken, D.E.L.
Betaine:homocysteine methyltransferase - a new assay for the liver enzyme and its absence from human skin fibroblasts and peripheral blood lymphocytes
Clin. Chim. Acta
204
239-249
1991
Homo sapiens, Ovis aries, Gallus gallus
brenda
Skiba, W.E.; Wells, M.S.; Mangum, J.H.; Awad, W.M.
Betaine-homocysteine S-methyltransferase (human)
Methods Enzymol.
143
384-388
1987
Homo sapiens, Equus caballus
brenda
Finkelstein, J.D.; Harris, B.J.; Kyle, W.E.
Methionine metabolism in mammals: kinetic study of betaine-homocysteine methyltransferase
Arch. Biochem. Biophys.
153
320-324
1972
Rattus norvegicus
brenda
Skiba, W.E.; Taylor, M.P.; Wells, M.S.; Mangum, J.H.; Awad, W.M.
Human hepatic methionine biosynthesis. Purification and characterization of betaine:homocysteine S-methyltransferase
J. Biol. Chem.
257
14944-14948
1982
Homo sapiens
brenda
Lee, K.H.; Cava, M.; Amiri, P.; Ottoboni, T.; Lindquist, R.N.
Betaine:homocysteine methyltransferase from rat liver: purification and inhibition by a boronic acid substrate analog
Arch. Biochem. Biophys.
292
77-86
1992
Rattus norvegicus, Rattus norvegicus Sprague-Dawley
brenda
Finkelstein, J.D.; Martin, J.J.
Inactivation of betaine-homocysteine methyltransferase by adenosylmethionine and adenosylethionine
Biochem. Biophys. Res. Commun.
118
14-19
1984
Rattus norvegicus
brenda
Awad, W.M.; Whitney, P.L.; Skiba, W.E.; Mangum, J.H.; Wells, M.S.
Evidence for direct methyl transfer in betaine: homocysteine S-methyl-transferase
J. Biol. Chem.
258
12790-12792
1983
Homo sapiens
brenda
Finkelstein, J.D.; Kyle, W.E.; Harris, B.J.
Methionine metabolism in mammals: regulatory effects of S-adenosylhomocysteine
Arch. Biochem. Biophys.
165
774-779
1974
Rattus norvegicus
brenda
Gonzalez, B.; Pajares, M.A.; Too, H.P.; Garrido, F.; Blundell, T.L.; Sanz-Aparicio, J.
Crystallization and preliminary x-ray study of recombinant betaine-homocysteine S-methyltransferase from rat liver
Acta Crystallogr. Sect. D
58
1507-1510
2002
Rattus norvegicus
brenda
Bose, N.; Momany, C.
Crystallization and preliminary x-ray crystallographic studies of recombinant human betaine-homocysteine S-methyltransferase
Acta Crystallogr. Sect. D
57
431-433
2001
Homo sapiens
brenda
Millian, N.S.; Garrow, T.A.
Human betaine-homocysteine methyltransferase is a zinc metalloenzyme
Arch. Biochem. Biophys.
356
93-98
1998
Homo sapiens
brenda
Emmert, J.L.; Garrow, T.A.; Baker, D.H.
Hepatic betaine-homocysteine methyltransferase activity in the chicken is influenced by dietary intake of sulfur amino acids, choline and betaine
J. Nutr.
126
2050-2058
1996
Gallus gallus
brenda
Garrow, T.A.
Purification, kinetic properties, and cDNA cloning of mammalian betaine-homocysteine methyltransferase
J. Biol. Chem.
271
22831-22838
1996
Homo sapiens (Q93088), Homo sapiens, Sus scrofa (Q95332), Sus scrofa
brenda
Rao, P.V.; Garrow, T.A.; John, F.; Garland, D.; Millian, N.S.; Zigler, J.S., Jr.
Betaine-homocysteine methyltransferase is a developmentally regulated enzyme crystallin in rhesus monkey lens
J. Biol. Chem.
273
30669-30674
1998
Macaca mulatta
brenda
Breksa, A.P.; Garrow, T.A.
Recombinant human liver betaine-homocysteine S-methyltransferase: Identification of three cysteine residues critical for zinc binding
Biochemistry
38
13991-13998
1999
Homo sapiens
brenda
Incharoensakdi, A.; Waditee, R.
Degradation of glycinebetaine by betaine-homocysteine methyltransferase in Aphanothece halophytica: effect of salt downshock and starvation
Curr. Microbiol.
41
227-231
2000
Aphanothece halophytica
brenda
Waditee, R.; Incharoensakdi, A.
Purification and kinetic properties of betaine-homocysteine methyltransferase from Aphanothece halophytica
Curr. Microbiol.
43
107-111
2001
Aphanothece halophytica
brenda
Bose, N.; Greenspan, P.; Momany, C.
Expression of recombinant human betaine:homocysteine S-methyltransferase for x-ray crystallographic studies and further characterization of interaction with S-adenosylmethionine
Protein Expr. Purif.
25
73-80
2002
Homo sapiens
brenda
Delgado-Reyes, C.V.; Wallig, M.A.; Garrow, T.A.
Immunohistochemical detection of betaine-homocysteine S-methyltransferase in human, pig, and rat liver and kidney
Arch. Biochem. Biophys.
393
184-186
2001
Homo sapiens, Rattus norvegicus, Sus scrofa
brenda
Breksa, A.P.; Garrow, T.A.
Random mutagenesis of the zinc-binding motif of betaine-homocysteine methyltransferase reveals that Gly214 Is essential
Arch. Biochem. Biophys.
399
73-80
2002
Homo sapiens
brenda
Delgado-Reyes, C.V.; Garrow, T.A.
High sodium chloride intake decreases betaine-homocysteine S-methyltransferase expression in guinea pig liver and kidney
Am. J. Physiol.
288
R182-187
2005
Sus scrofa
brenda
Szegedi, S.S.; Garrow, T.A.
Oligomerization is required for betaine-homocysteine S-methyltransferase function
Arch. Biochem. Biophys.
426
32-42
2004
Homo sapiens (Q93088)
brenda
Gonzalez, B.; Campillo, N.; Garrido, F.; Gasset, M.; Sanz-Aparicio, J.; Pajares, M.A.
Active-site-mutagenesis study of rat liver betaine-homocysteine S-methyltransferase
Biochem. J.
370
945-952
2003
Rattus norvegicus (O09171)
brenda
Garrido, F.; Gasset, M.; Sanz-Aparicio, J.; Alfonso, C.; Pajares, M.A.
Rat liver betaine homocysteine S-methyltransferase equilibrium unfolding: insights into intermediate structure through tryptophan substitutions
Biochem. J.
391
589-599
2005
Rattus norvegicus
brenda
Miller, C.M.; Szegedi, S.S.; Garrow, T.A.
Conformation-dependent inactivation of human betaine-homocysteine S-methyltransferase by hydrogen peroxide in vitro
Biochem. J.
392
443-448
2005
Homo sapiens (Q93088), Homo sapiens
brenda
Forestier, M.; Banninger, R.; Reichen, J.; Solioz, M.
Betaine homocysteine methyltransferase: gene cloning and expression analysis in rat liver cirrhosis
Biochim. Biophys. Acta
1638
29-34
2003
Rattus norvegicus
brenda
Collinsova, M.; Castro, C.; Garrow, T.A.; Yiotakis, A.; Dive, V.; Jiracek, J.
Combining combinatorial chemistry and affinity chromatography: highly selective inhibitors of human betaine: homocysteine S-methyltransferase
Chem. Biol.
10
113-122
2003
Homo sapiens
brenda
Ichikawa, A.; Ohashi, Y.; Terada, S.; Natsuka, S.; Ikura, K.
In vitro modification of betaine-homocysteine S-methyltransferase by tissue-type transglutaminase
Int. J. Biochem. Cell Biol.
36
1981-1992
2004
Sus scrofa
brenda
Gonzalez, B.; Pajares, M.A.; Martinez-Ripoll, M.; Blundell, T.L.; Sanz-Aparicio, J.
Crystal structure of rat liver betaine homocysteine S-methyltransferase reveals new oligomerization features and conformational changes upon substrate binding
J. Mol. Biol.
338
771-782
2004
Rattus norvegicus (O09171)
brenda
Ratnam, S.; Wijekoon, E.P.; Hall, B.; Garrow, T.A.; Brosnan, M.E.; Brosnan, J.T.
Effects of diabetes and insulin on betaine-homocysteine S-methyltransferase expression in rat liver
Am. J. Physiol. Endocrinol. Metab.
290
E933-E939
2006
Rattus norvegicus
brenda
Nieman, K.M.; Hartz, C.S.; Szegedi, S.S.; Garrow, T.A.; Sparks, J.D.; Schalinske, K.L.
Folate status modulates the induction of hepatic glycine N-methyltransferase and homocysteine metabolism in diabetic rats
Am. J. Physiol. Endocrinol. Metab.
291
E1235-E1242
2006
Rattus norvegicus
brenda
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
Rattus norvegicus, Rattus norvegicus (O09171), Mus musculus
brenda
Sparks, J.D.; Collins, H.L.; Chirieac, D.V.; Cianci, J.; Jokinen, J.; Sowden, M.P.; Galloway, C.A.; Sparks, C.E.
Hepatic very-low-density lipoprotein and apolipoprotein B production are increased following in vivo induction of betaine-homocysteine S-methyltransferase
Biochem. J.
395
363-371
2006
Rattus norvegicus
brenda
Ou, X.; Yang, H.; Ramani, K.; Ara, A.I.; Chen, H.; Mato, J.M.; Lu, S.C.
Inhibition of human betaine-homocysteine methyltransferase expression by S-adenosylmethionine and methylthioadenosine
Biochem. J.
401
87-96
2007
Homo sapiens (Q6EI07), Homo sapiens
brenda
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
brenda
Jiracek, J.; Collinsova, M.; Rosenberg, I.; Budesinsky, M.; Protivinska, E.; Netusilova, H.; Garrow, T.A.
S-alkylated homocysteine derivatives: new inhibitors of human betaine-homocysteine S-methyltransferase
J. Med. Chem.
49
3982-3989
2006
Homo sapiens
brenda
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
brenda
Slow, S.; Garrow, T.A.
Liver choline dehydrogenase and kidney betaine-homocysteine methyltransferase expression are not affected by methionine or choline intake in growing rats
J. Nutr.
136
2279-2283
2006
Rattus norvegicus
brenda
Pillai, P.B.; Fanatico, A.C.; Beers, K.W.; Blair, M.E.; Emmert, J.L.
Homocysteine remethylation in young broilers fed varying levels of methionine, choline, and betaine
Poult. Sci.
85
90-95
2006
Gallus gallus
brenda
Ji, C.; Shinohara, M.; Vance, D.; Than, T.A.; Ookhtens, M.; Chan, C.; Kaplowitz, N.
Effect of transgenic extrahepatic expression of betaine-homocysteine methyltransferase on alcohol or homocysteine-induced fatty liver
Alcohol. Clin. Exp. Res.
32
1049-1058
2008
Homo sapiens
brenda
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
brenda
Ji, C.; Shinohara, M.; Kuhlenkamp, J.; Chan, C.; Kaplowitz, N.
Mechanisms of protection by the betaine-homocysteine methyltransferase/betaine system in HepG2 cells and primary mouse hepatocytes
Hepatology
46
1586-1596
2007
Homo sapiens (Q93088)
brenda
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
Mus musculus, Homo sapiens
brenda
Ananth, C.V.; Elsasser, D.A.; Kinzler, W.L.; Peltier, M.R.; Getahun, D.; Leclerc, D.; Rozen, R.R.; Rozen, R.R.
Polymorphisms in methionine synthase reductase and betaine-homocysteine S-methyltransferase genes: risk of placental abruption
Mol. Genet. Metab.
91
104-110
2007
Homo sapiens
brenda
Li, F.; Feng, Q.; Lee, C.; Wang, S.; Pelleymounter, L.L.; Moon, I.; Eckloff, B.W.; Wieben, E.D.; Schaid, D.J.; Yee, V.; Weinshilboum, R.M.
Human betaine-homocysteine methyltransferase (BHMT) and BHMT2: common gene sequence variation and functional characterization
Mol. Genet. Metab.
94
326-335
2008
Homo sapiens
brenda
Mercer, C.; Kaliappan, A.; Dennis, P.
Macroautophagy-dependent, intralysosomal cleavage of a betaine homocysteine methyltransferase fusion protein requires stable multimerization
Autophagy
4
185-194
2008
Homo sapiens
brenda
Kharbanda, K.K.; Vigneswara, V.; McVicker, B.L.; Newlaczyl, A.U.; Bailey, K.; Tuma, D.; Ray, D.E.; Carter, W.G.
Proteomics reveal a concerted upregulation of methionine metabolic pathway enzymes, and downregulation of carbonic anhydrase-III, in betaine supplemented ethanol-fed rats
Biochem. Biophys. Res. Commun.
381
523-527
2009
Rattus norvegicus
brenda
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
brenda
Xu, Y.Y.; Guan, D.Y.; Yang, M.; Wang, H.; Shen, Z.H.
All-trans-retinoic acid intensifies endoplasmic reticulum stress in N-acetylglucosaminyltransferase V repressed human hepatocarcinoma cells by perturbing homocysteine metabolism
J. Cell. Biochem.
109
468-477
2010
Homo sapiens
brenda
Vanek, V.; Budesinsky, M.; Kabeleova, P.; Sanda, M.; Kozisek, M.; Hanclova, I.; Mladkova, J.; Brynda, J.; Rosenberg, I.; Koutmos, M.; Garrow, T.A.; Jiracek, J.
Structure-activity study of new inhibitors of human betaine-homocysteine S-methyltransferase
J. Med. Chem.
52
3652-3665
2009
Homo sapiens
brenda
Ohuchi, S.; Morita, T.; Mori, M.; Sugiyama, K.
Hepatic cystathionine beta-synthase activity does not increase in response to methionine supplementation in rats fed a low casein diet: association with plasma homocysteine concentrations
J. Nutr. Sci. Vitaminol.
55
178-185
2009
Rattus norvegicus
brenda
Brosnan, J.T.; Wijekoon, E.P.; Warford-Woolgar, L.; Trottier, N.L.; Brosnan, M.E.; Brunton, J.A.; Bertolo, R.F.
Creatine synthesis is a major metabolic process in neonatal piglets and has important implications for amino acid metabolism and methyl balance
J. Nutr.
139
1292-1297
2009
Sus scrofa
brenda
Korinek, M.; Sistek, V.; Mladkova, J.; Mikes, P.; Jiracek, J.; Selicharova, I.
Quantification of homocysteine-related metabolites and the role of betaine-homocysteine S-methyltransferase in HepG2 cells
Biomed. Chromatogr.
27
111-121
2013
Homo sapiens (Q93088)
brenda
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
brenda
Fridman, O.; Morales, A.V.; Bortoni, L.E.; Turk-Noceto, P.C.; Prieto, E.A.
Corticoadrenal activity in rat regulates betaine-homocysteine S-methyltransferase expression with opposite effects in liver and kidney
J. Biosci.
37
115-123
2012
Rattus norvegicus
brenda
Mladkova, J.; Vanek, V.; Budesinsky, M.; Elbert, T.; Demianova, Z.; Garrow, T.A.; Jiracek, J.
Double-headed sulfur-linked amino acids as first inhibitors for betaine-homocysteine S-methyltransferase 2
J. Med. Chem.
55
6822-6831
2012
Homo sapiens
brenda
Selicharova, I.; Korinek, M.; Demianova, Z.; Chrudinova, M.; Mladkova, J.; Jiracek, J.
Effects of hyperhomocysteinemia and betaine-homocysteine S-methyltransferase inhibition on hepatocyte metabolites and the proteome
Biochim. Biophys. Acta
1834
1596-1606
2013
Homo sapiens (Q93088), Homo sapiens
brenda
Ma, H.; Ning, J.; Jin, X.; Mao, C.; Bu, X.; Wang, M.; Liu, H.; Wang, K.; Lausted, C.; Hood, L.; Chen, J.; Hu, Z.
Betaine homocysteine methyltransferase (BHMT) as a specific and sensitive blood marker for acute liver injury
Biomarkers
19
578-584
2014
Homo sapiens
brenda
Van den Bergh, K.; Vercammen, M.; Regenass, S.; Derua, R.; Vermeersch, P.; Pokreisz, P.; Ocmant, A.; de Beeck, K.; Janssens, S.; Waelkens, E.; Bossuyt, X.
Betaine homocysteine methyl transferase 1, a novel auto-antigen associated with anti-Golgi immune reactivity
Clin. Chim. Acta
413
105-108
2012
Homo sapiens
brenda
Picha, J.; Vanek, V.; Budesinsky, M.; Mladkova, J.; Garrow, T.A.; Jiracek, J.
The development of a new class of inhibitors for betaine-homocysteine S-methyltransferase
Eur. J. Med. Chem.
65
256-275
2013
Homo sapiens (Q93088), Homo sapiens
brenda
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
brenda
Ganu, R.; Garrow, T.; Koutmos, M.; Rund, L.; Schook, L.B.
Splicing variants of the porcine betaine-homocysteine S-methyltransferase gene: implications for mammalian metabolism
Gene
529
228-237
2013
Sus scrofa
brenda
Zhang, Y.; Zhu, T.; Wang, L.; Pan, Y.; Zhang, S.
Homocysteine homeostasis and betaine-homocysteine S-methyltransferase expression in the brain of hibernating bats
PLoS ONE
8
e85632
2013
Myotis pilosus (A0A059PVS2)
brenda
Mladkova, J.; Hladilkova, J.; Diamond, C.E.; Tryon, K.; Yamada, K.; Garrow, T.A.; Jungwirth, P.; Koutmos, M.; Jiracek, J.
Specific potassium ion interactions facilitate homocysteine binding to betaine-homocysteine S-methyltransferase
Proteins
82
2552-2564
2014
Homo sapiens (Q93088), Homo sapiens
brenda
Ahn, C.W.; Jun, D.S.; Na, J.D.; Choi, Y.J.; Kim, Y.C.
Alleviation of hepatic fat accumulation by betaine involves reduction of homocysteine via up-regulation of betaine-homocysteine methyltransferase (BHMT)
Biochem. Biophys. Res. Commun.
477
440-447
2016
Rattus norvegicus
brenda
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
brenda
Coleman, D.N.; Vailati-Riboni, M.; Elolimy, A.A.; Cardoso, F.C.; Rodriguez-Zas, S.L.; Miura, M.; Pan, Y.X.; Loor, J.J.
Hepatic betaine-homocysteine methyltransferase and methionine synthase activity and intermediates of the methionine cycle are altered by choline supply during negative energy balance in Holstein cows
J. Dairy Sci.
102
8305-8318
2019
Bos taurus
brenda
Zhou, Z.; Garrow, T.A.; Dong, X.; Luchini, D.N.; Loor, J.J.
Hepatic activity and transcription of betaine-homocysteine methyltransferase, methionine synthase, and cystathionine synthase in periparturient dairy cows are altered to different extents by supply of methionine and choline
J. Nutr.
147
11-19
2017
Bos taurus
brenda
Saande, C.J.; Pritchard, S.K.; Worrall, D.M.; Snavely, S.E.; Nass, C.A.; Neuman, J.C.; Luchtel, R.A.; Dobiszewski, S.; Miller, J.W.; Vailati-Riboni, M.; Loor, J.J.; Schalinske, K.L.
Dietary egg protein prevents hyperhomocysteinemia via upregulation of hepatic betaine-homocysteine S-methyltransferase activity in folate-restricted rats
J. Nutr.
149
1369-1376
2019
Rattus norvegicus
brenda
Garrido, F.; Pacheco, M.; Vargas-Martinez, R.; Velasco-Garcia, R.; Jorge, I.; Serrano, H.; Portillo, F.; Vazquez, J.; Pajares, M.A.
Identification of hepatic protein-protein interaction targets for betaine homocysteine S-methyltransferase
PLoS ONE
13
e0199472
2018
Rattus norvegicus (O09171), Rattus norvegicus
brenda
Liu, J.; Liu, Y.; Chen, Y.; Liu, Y.; Huang, C.; Luo, Y.; Wang, X.
Betaine alleviates nonalcoholic fatty liver disease (NAFLD) via a manner involving BHMT/FTO/m6A/ PGC1? signaling
J. Nutr. Biochem.
134
109738
2024
Mus musculus (O35490)
brenda
Liu, C.; Zhang, Y.; Wang, Y.; Wang, N.; Xu, J.; Liang, X.; Xiong, J.; Lu, S.; Zhou, P.; Liu, J.; Chen, S.
Betaine-homocysteine methyltransferase promotes adipocyte commitment and insulin resistance via p38 MAPK/Smad signaling
Obesity (Silver Spring)
31
1569-1583
2023
Homo sapiens (Q93088), Mus musculus (O35490)
brenda
Sternbach, S.; West, N.; Singhal, N.K.; Clements, R.; Basu, S.; Tripathi, A.; Dutta, R.; Freeman, E.J.; McDonough, J.
The BHMT-betaine methylation pathway epigenetically modulates oligodendrocyte maturation
PLoS ONE
16
e0250486
2021
Homo sapiens (Q93088), Rattus norvegicus
brenda
EXTERNAL LINKS (specific for EC-Number 2.1.1.5)
html completed
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2026.1 (March 2026)
About BRENDA
Social media
Help
Survey
Download
Contribution
Legal
Curated at
Member of
![DSMZ Digital Diversity]()
![Global Core Biodata Resource]()
![ELIXIR Core Data Resource]()
![German Network for Bioinformatics Infrastructure]()
