BHMT Antibodies

Background

BHMT is a cytoplasmic enzyme protein present in the liver and kidneys of vertebrates. This enzyme uses zinc as a cofactor to catalyze the methyl transfer reaction between betaine and homocysteine, generating methionine and dimethyl glycine, thereby participating in the body's methyl metabolism and the conversion process of homocysteine. Mammals rely on BHMT to maintain the homeostasis of the methionine cycle, which is particularly crucial for liver metabolic balance when dietary methyl donors are insufficient. This enzyme was first purified and identified in 1995. Its crystal structure was analyzed by X-ray diffraction in 2002, revealing a unique tetramer conformation and substrate binding characteristics. As a key regulatory enzyme in the methionine cycle, the structural and functional studies of BHMT provide an important molecular basis for understanding metabolic diseases, oxidative stress and nutritional intervention.

Structure Function Application Advantage Our Products

Structure of BHMT

BHMT is a homologous tetramer protein with a molecular weight of approximately 45 kDa. Its monomer is composed of approximately 400 amino acid residues and has a highly conserved sequence in different mammals.

Species	Human	Rat	Mouse	Pig
Molecular Weight (kDa)	45.2	44.8	44.9	45.1
Primary Structural Differences	Zinc-containing cofactor binding domain	Relatively high catalytic activity	With the human homology of 90%	Substrate specificity is similar

Each monomer of this enzyme contains a zinc ion cofactor, which is stably bound through a cysteine residue coordination bond. Its tertiary structure forms a typical methyltransferase fold, consisting of multiple parallel β -sheets and α -helical active pockets, which achieve the methyl transfer reaction between betaine and homocysteine through conserved catalytic residues. The dimer interface stabilizes through hydrophobic interactions and hydrogen bond networks, and eventually assembles into a tetramer with complete catalytic function.

Fig. 1:Mapping positively selected amino acids on the BHMT structure. Fig. 1 Mapping of amino acids with signatures of positive selection on the structure of BHMT.¹

Key structural properties of BHMT:

Typical folded structure of methyltransferase
Zinc ion cofactors are stabilized through cysteine residue coordination
Hydrophobic active pockets contain betaine and homocysteine substrates

Functions of BHMT

The core function of BHMT is to catalyze methyl transfer reactions to maintain the methionine cycle. In addition, it is also involved in a variety of physiological processes, including the regulation of homocysteine metabolism and liver lipid metabolism.

Function	Description
Synthesis of methyl donors	Catalyze the reaction of betaine with homocysteine to form methionine and dimethyl glycine, providing an essential source of methyl groups.
Homocysteine clearance	Effectively reduce the concentration of homocysteine in the blood, lowering the risk of cardiovascular diseases and neuropathy.
Regulation of oxidative stress	By maintaining cellular methylation balance, indirectly involved in antioxidant defense mechanisms.
Regulation of lipid metabolism	The phospholipid synthesis and lipoprotein metabolism in the liver, associated with fatty liver development.
Embryo development support	Providing methyl donors for development plays an important role in regulating early nervous system and organ formation.

The reaction catalyzed by this enzyme follows the ping-pong double substrate mechanism. Its kinetic characteristics are characterized by high affinity for both betaine and homocysteine, enabling it to efficiently maintain methyl metabolic homeostasis at low substrate concentrations.

Applications of BHMT and BHMT Antibody in Literature

1. Zeng, Liang, et al. "SDC1-TGM2-FLOT1-BHMT complex determines radiosensitivity of glioblastoma by influencing the fusion of autophagosomes with lysosomes." Theranostics 13.11 (2023): 3725. https://doi.org/10.7150/thno.81999

This study reveals that in glioblastoma, SDC1 mediates the transport of TGM2 to lysosomes and binds to BHMT on autophagosomes, promoting autophagosome-lysosome fusion, thereby maintaining autophagic flux through BHMT and enhancing radiotherapy resistance. This mechanism provides a new strategy for targeted radiotherapy resistance.

2. Sternbach, Sarah, et al. "The BHMT-betaine methylation pathway epigenetically modulates oligodendrocyte maturation." PloS one 16.5 (2021): e0250486. https://doi.org/10.1371/journal.pone.0250486

Research has found that BHMT is expressed in the nuclei of oligodendrocytes and its expression increases under oxidative stress. Betaine enhances histone and DNA methylation activity through BHMT, promotes the expression of oligodendrocyte maturation genes, and may interact with DNMT3a, indicating that the availability of methyl donors affects the epigenetic regulation and maturation process of oligodendrocytes.

3. Luo, Manjun, et al. "Association and interaction effect of BHMT gene polymorphisms and maternal dietary habits with ventricular septal defect in offspring." Nutrients 14.15 (2022): 3094. https://doi.org/10.3390/nu14153094

Research has found that polymorphisms at the rs1316753 and rs1915706 loci of the maternal BHMT gene can increase the risk of ventricular septal defect in offspring and have a significant interaction with legume intake. Excessive intake of smoked, grilled, fried and pickled foods by mothers significantly increases the risk, while regular consumption of fruits, fish, shrimp, eggs and the like reduces the risk.

4. Ganu, Radhika S., et al. "Evolutionary analyses and natural selection of betaine-homocysteine S-methyltransferase (BHMT) and BHMT2 genes." PLoS One 10.7 (2015): e0134084. https://doi.org/10.1371/journal.pone.0134084

Research has found that BHMT is widely present in deuterostomes, while BHMT2 is only found in mammals, and the two exist in tandem. After gene replication, the evolution rate of BHMT2 accelerates, and multiple sites are affected by positive selection, which may be related to enzyme function and changes in the oligomerization domain.

5. Yamashima, Tetsumori, et al. "Vegetable oil-peroxidation product 'hydroxynonenal' causes hepatocyte injury and steatosis via Hsp70. 1 and BHMT disorders in the monkey liver." nutrients 15.8 (2023): 1904. https://doi.org/10.3390/nu15081904

Research has found that the increased lysis and down-regulation of BHMT and Hsp70.1 in the liver are closely related to the rupture of lysosomal membranes, organelle damage and steatosis induced by hydroxynonenal. The carbonylation of BHMT significantly increases, which may exacerbate hepatocyte degeneration and lipid accumulation by affecting endoplasmic reticulum function.

Creative Biolabs: BHMT Antibodies for Research

Creative Biolabs specializes in the production of high-quality BHMT antibodies for research and industrial applications. Our portfolio includes monoclonal antibodies tailored for ELISA, Flow Cytometry, Western blot, immunohistochemistry, and other diagnostic methodologies.

Custom BHMT Antibody Development: Tailor-made solutions to meet specific research requirements.
Bulk Production: Large-scale antibody manufacturing for industry partners.
Technical Support: Expert consultation for protocol optimization and troubleshooting.
Aliquoting Services: Conveniently sized aliquots for long-term storage and consistent experimental outcomes.

For more details on our BHMT antibodies, custom preparations, or technical support, contact us at email.

Reference

Ganu, Radhika S., et al. "Evolutionary analyses and natural selection of betaine-homocysteine S-methyltransferase (BHMT) and BHMT2 genes." PLoS One 10.7 (2015): e0134084. https://doi.org/10.1371/journal.pone.0134084