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BETAINE-HOMOCYSTEINE METHYLTRANSFERASE
BETAINE-HOMOCYSTEINE S-METHYLTRANSFERASE
EC Number: 2.1.1.5
CAS Number: 9029-78-1
In the field of enzymology, a betaine-homocysteine S-methyltransferase also known as betaine-homocysteine methyltransferase (BHMT) is a zinc metallo-enzyme that catalyzes the transfer of a methyl group from trimethylglycine and a hydrogen ion from homocysteine to produce dimethylglycine and methionine respectively:
Trimethylglycine (methyl donor) + homocysteine (hydrogen donor) → dimethylglycine (hydrogen receiver) + methionine (methyl receiver)
This enzyme belongs to the family of transferases, specifically those transferring one-carbon group methyltransferases.
This enzyme participates in the metabolism of glycine, serine, threonine and also methionine.
Betaine-homocysteine methyltransferase (BHMT) is involved in the regulation of homocysteine metabolism.
Betaine-homocysteine methyltransferase converts betaine and homocysteine to dimethylglycine and methionine, respectively.
This reaction is also required for the irreversible oxidation of choline. BHMT requires a thiol reducing agent for its activity.
The catalytic zinc of BHMT is bound by three thiolates and one hydroxyl group.
A disulphide bond is formed between two of the three zinc-binding ligands when BHMT is inactive.
BHMT regulates homocysteine levels in the liver.
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.
Betaine-homocysteine methyltransferase also has a generalized effect on liver lipids by inducing ApoB expression and increasing S-adenosylmethionine/S-adenosylhomocysteine.
However, the peripheral metabolism of homocysteine protects the liver without the direct action of BHMT in the liver.
The human betaine-homocysteine methyltransferase-2 is also a zinc metalloenzyme that uses S-methylmethionine (SMM) as a methyl donor for the methylation of homocysteine.
Unlike the highly homologous BHMT, BHMT-2 cannot use betaine as a substrate.
Also includes homocysteine S-methyltransferase, which converts S-adenosylmethionine to methionine; selenocysteine methyltransferase, which methylates DL- and L-selenocysteine, DL-homocysteine, and DL- and L-cysteine; and S-methylmethionine-homocysteine S-methyltransferase BHMT2, which converts converts homocysteine to methionine.
Enables betaine-homocysteine S-methyltransferase activity and identical protein binding activity.
Involved in methionine biosynthetic process; protein methylation; and response to organonitrogen compound.
Located in cytosol and nucleus.
Part of protein-containing complex.
Betaine homocysteine S-methyltransferase: just a regulator of homocysteine metabolism?
Betaine homocysteine methyltransferase (BHMT), a Zn(2+)-dependent thiolmethyltransferase, contributes to the regulation of homocysteine levels, increases in which are considered a risk factor for cardiovascular diseases.
Most plasma homocysteine is generated through the liver methionine cycle, in which BHMT metabolizes approximately 25% of this non-protein amino acid.
This process allows recovery of one of the three methylation equivalents used in phosphatidylcholine synthesis through transmethylation, a major homocysteine-producing pathway.
Although BHMT has been known for over 40 years, the difficulties encountered in its isolation precluded detailed studies until very recently.
Thus, the last 10 years, since the sequence became available, have yielded extensive structural and functional data.
Moreover, recent findings offer clues for potential new functions for BHMT.
The purpose of this review is to provide an integrated view of the knowledge available on BHMT, and to analyze its putative roles in other processes through interactions uncover to date.
B Vitamins Intake and Plasma Homocysteine in Vegetarians:
In the methionine cycle, homocysteine is converted to methionine, and the enzyme involved is betaine homocysteine methyltransferase (BHMT).
This reaction is independent of the one that is mediated by MS and independent of vitamin B12 or the folate cycle.
In this case, methionine is regenerated from homocysteine by the transfer of a methyl group from trimethylglycine (TMG) to homocysteine.
Once TMG loses a methyl group to homocysteine, it converts to dimethylglycine (DMG).
In turn, homocysteine gains a methyl group and becomes methionine.
BHMT is a zinc metalloenzyme that uses preformed methyl groups from dietary TMG or from TMG derived from either dietary choline or choline synthesized through successive SAM-dependent methylations of phosphatidylethanolamine.
TMG may be an important methylating agent when the folate-dependent methylating pathway is impaired by ethanol ingestion, drugs, nutritional imbalances, or when TMG or choline levels are high.
The TMG reaction is considered to be a minor route since it can only take place in the liver and kidney of humans, as the enzyme involved, BHMT, has only been identified to be present in these organs.
TMG is obtainable from foods such as wheat bran, wheat germ, spinach, and beets.
Betaine-homocysteine methyltransferase can also be synthesized in the body from choline.
Total choline can be obtained from food such as beef liver, eggs, and soybeans in the form of choline phosphocholine, glycerophosphocholine, sphingomyelin, and phosphatidylcholine.
When total choline is taken up by tissues, it is either converted to TMG and then employed as an osmolyte and methyl donor, or it is phosphorylated and used for the synthesis of phospholipids.
The conversion of total choline to TMG is irreversible.
Isozymes of Betaine-homocysteine methyltransferase:
In humans, there are two isozymes, BHMT and BHMT2, each encoded by a separate gene.
Tissue distribution of Betaine-homocysteine methyltransferase:
BHMT is expressed most predominantly in the liver and kidney.
Clinical significance of Betaine-homocysteine methyltransferase:
Mutations in the BHMT gene are known to exist in humans.
Anomalies may influence the metabolism of homocysteine , which is implicated in disorders ranging from vascular disease, autism, and schizophrenia to neural tube birth defects such as spina bifida.
Identifiers of Betaine-homocysteine methyltransferase:
EC Number: 2.1.1.5
CAS Number: 9029-78-1
Synonmys of Betaine-homocysteine methyltransferase:
Bis(HexaMethylene Triamine Penta (Methylene Phosphonic Acid))
BHMTPMP
BHMT
BHMTPh.PN(Nax)
Bis(HexaMethylene Triamine Penta (Methylene Phosphonic Acid))
PARTIALLY NEUTRALISED SODIUM SALT OF BIS HEXAMETHYLENE
Bis(HexaMethylene Triamine Penta (Methylene Phosphonic Acid)) BHMTPMP
