Disease relevance of Bhmt

• Betaine homocysteine methyltransferase: gene cloning and expression analysis in rat liver cirrhosis [1].
• In conclusion, these findings establish a reduced BHMT enzyme activity in cirrhotic rat livers, which may explain the elevated plasma homocysteine levels in cirrhosis [1].
• We have previously reported a positive correlation between the expression of BHMT (betaine-homocysteine S-methyltransferase) and ApoB (apolipoprotein B) in rat hepatoma McA (McArdle RH-7777) cells [Sowden, Collins, Smith, Garrow, Sparks and Sparks (1999) Biochem. J. 341, 639-645] [2].
• Glycine betaine supplementation lowers homocysteine levels in homocystinuria and in chronic renal failure patients through methylation catalysed by betaine-homocysteine methyltransferase (BHMT) [3].

High impact information on Bhmt

• A diabetic state also increased the activity of the folate-independent homocysteine remethylation enzyme betaine-homocysteine S-methyltransferase, whereas the activity of the folate-dependent enzyme methionine synthase was diminished 52% [4].
• In contrast, RA treatment attenuated the streptozotocin-mediated increase in betaine-homocysteine S-methyltransferase, whereas methionine synthase activity remained diminished [4].
• Autolysosomal membrane-associated betaine homocysteine methyltransferase. Limited degradation fragment of a sequestered cytosolic enzyme monitoring autophagy [5].
• Methionine supplementation resulted in decreased hepatic levels of methyltetrahydrofolate-homocysteine methyltransferase and increased levels of methionine adenosyltransferase, betaine-homocysteine methyltransferase, and cystathionine synthase [6].
• Subsequent studies demonstrated that the adaptation from a high protein diet to a low protein diet is achieved by a significant increase in betaine homocysteine methyltransferase, and 83% reduction in cystathionine synthase, and a total decrease of 55% in the consumption of homocysteine [7].

Biological context of Bhmt

• A site-directed-mutagenesis study of putative active-site residues in rat liver betaine-homocysteine S-methyltransferase has been carried out [8].
• A partial BHMT clone was isolated by screening of a cDNA library with the differential display fragment [1].
• This restoration of hepatocellular SAM:SAH ratio by betaine supplementation was associated with increases in the activity, enzyme mass and gene expression of the enzyme, betaine homocysteine methyltransferase (BHMT), that remethylates homocysteine [9].
• The mechanism of betaine action appeared to be via the methylation reaction catalyzed by betaine-homocysteine-methyltransferase [10].
• Selenium deficiency decreased (P < 0.05) colonic DNA methylation and the activities of liver DNA methyltransferase and betaine homocysteine methyltransferase and increased plasma glutathione concentrations [11].

Anatomical context of Bhmt

• Enzyme assays in crude liver homogenates showed a similar reduction in BHMT activity in bile duct ligated rat livers [1].
• In mammals, betaine of the mitochondrial matrix is used in the cytosol by betaine-homocysteine S-methyltransferase for methionine synthesis [12].
• Association of betaine-homocysteine S-methyltransferase with microtubules [12].
• The association of betaine-homocysteine S-methyltransferase with the cytoskeleton may functionally integrate the mitochondrial and cytoplasmic compartments of choline degradation [12].
• Leupeptin-induced appearance of partial fragment of betaine homocysteine methyltransferase during autophagic maturation in rat hepatocytes [13].

Associations of Bhmt with chemical compounds

• These results indicate that in sheep 5-methyltetrahydrofolate-homocysteine methyltransferase plays a significant role in hepatic methionine synthesis along with betaine-homocysteine methyltransferase [14].
• Rat liver betaine-homocysteine S-methyltransferase equilibrium unfolding: insights into intermediate structure through tryptophan substitutions [15].
• Equilibrium folding of rat liver BHMT (betaine-homocysteine methyltransferase), a TIM (triosephosphate isomerase)-barrel tetrameric protein, has been studied using urea as denaturant [15].
• Regulation of hepatic betaine-homocysteine methyltransferase by dietary betaine [16].
• The level of betaine-homocysteine methyltransferase increases in the livers of rats fed diets supplemented with betaine or choline [16].

Other interactions of Bhmt

• The cDNA encoding rat betaine-homocysteine S-methyltransferase (BHMT) was isolated through production of monoclonal antibodies against protein fractions enriched with apolipoprotein B (apo B)-mRNA-editing complexes [17].
• The important features of the enzymes involved in methionine synthesis in sheep were found to be the low activity of betaine-homocysteine methyltransferase and the high activity of 5-methyltetrahydrofolate-homocysteine methyltransferase [14].
• This was confirmed by confocal laser scanning microscopy of HepG2 cells labeled with betaine-homocysteine S-methyltransferase- and alpha-tubulin-specific monoclonal antibodies [12].
• Nanospray tandem mass spectrometry and N-terminal amino acid sequencing of microtubule-associated proteins from rat liver tubulin revealed that betaine-homocysteine S-methyltransferase is microtubule associated [12].

Analytical, diagnostic and therapeutic context of Bhmt

• By Western blotting, BHMT could be detected in crude liver homogenates of control animals, but was reduced to below the limit of detection in cirrhotic livers [1].
• BHMT mRNA levels were reduced to 29+/-23% in established liver cirrhosis induced by bile duct ligation (BDL) as compared to controls [1].
• Combining immunoblotting and reverse transcriptase-polymerase chain reaction analyses, we identified the 44-kDa peptide as the intact subunit of betaine homocysteine methyltransferase and the 35- and 32-kDa peptides as two proteolytic fragments [5].
• Crystallization and preliminary X-ray study of recombinant betaine-homocysteine S-methyltransferase from rat liver [18].
• An endpoint assay for BHMT activity was also developed, by measuring the N,N-dimethylglycine produced after incubation with 2 mM glycine betaine and homocysteine (CV=5.3%, n = 6) with a detection limit of 2 nkatal [19].

References