BHMT Human
Description
Genetic Variants and Phenotypic Correlations
Genome-wide studies have identified SNPs significantly associated with BHMT activity:
Evolutionary Divergence
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Gene Duplication: BHMT2 arose from a duplication event at the base of the mammalian lineage .
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Accelerated Evolution: BHMT2 exhibits faster evolutionary rates compared to BHMT, suggesting functional divergence .
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Conservation: Critical residues (e.g., Trp44, Ser77) in the active site are conserved across deuterostomes .
Hyperhomocysteinemia and Vascular Disease
BHMT deficiency is implicated in elevated homocysteine levels, a risk factor for:
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Neural Tube Defects: Spina bifida (odds ratio: 1.8–2.3 in maternal hyperhomocysteinemia) .
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Neuropsychiatric Disorders: Autism and schizophrenia linked to altered methylation patterns .
Role in Oligodendrocyte Function
Recent studies highlight BHMT's nuclear localization in oligodendrocytes, where it:
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Modulates histone H3K4 trimethylation (H3K4me3) and DNA methylation via DNMT3a interaction .
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Enhances expression of maturation genes (SOX10, NKX-2.2) under oxidative stress .
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Betaine supplementation rescues HMT/DNMT activity in BHMT-dependent manner (1.5–2.0-fold increase) .
Inhibitor Development
Potent BHMT inhibitors (e.g., S-alkylated homocysteine derivatives) mimic transition-state analogs:
| Inhibitor | Kₐ (nM) | Mechanism |
|---|---|---|
| Compound 1 | 12 | Competitive inhibition of betaine binding |
| Compound 3 | 8 | Dual sulfur substitution enhances potency |
Betaine as a Methyl Donor
Clinical trials demonstrate betaine’s efficacy in:
Future Directions
Product Specs
Product Science Overview
BHMT is part of the enzyme family [Pfam02574], which utilizes catalytic zinc to activate thiol or selenol substrates to thiolate or selenate anions prior to methyl transfer . The enzyme’s primary function is to maintain homocysteine levels in the body by converting it into methionine, an essential amino acid. Elevated homocysteine levels are associated with cardiovascular diseases, making BHMT a critical enzyme for cardiovascular health .
Recombinant BHMT refers to the enzyme produced through recombinant DNA technology, which allows for the production of human proteins in non-human cells. This technology is widely used in research and therapeutic applications to study the enzyme’s function and to develop treatments for diseases related to homocysteine metabolism .
BHMT and its closely related enzyme, BHMT-2, have evolved to perform specific functions in the methionine cycle. BHMT-2, although highly homologous to BHMT, cannot use betaine as a methyl donor and instead uses S-methylmethionine (SMM) for the methylation of homocysteine . This specialization highlights the evolutionary adaptation of these enzymes to different substrates and functions within the methionine cycle.
The clinical significance of BHMT lies in its role in regulating homocysteine levels. Abnormalities in BHMT function can lead to hyperhomocysteinemia, which is linked to various health issues, including cardiovascular diseases, neural tube defects, and cognitive impairments. Understanding the function and regulation of BHMT is crucial for developing therapeutic strategies to manage these conditions .
Research on recombinant BHMT has provided insights into its structure, function, and regulation. Studies have demonstrated the enzyme’s role in homocysteine metabolism and its potential as a therapeutic target. Recombinant BHMT is also used in biochemical assays to study the effects of various compounds on homocysteine levels and to develop drugs that can modulate its activity .
