Abstract:
:Betaine-homocysteine methyltransferase (BHMT) catalyzes the remethylation of homocysteine. BHMT2 encodes a protein 73% identical in amino acid sequence to BHMT, but the function of BHMT2 remains unclear. We set out to identify and functionally characterize common genetic variation in BHMT and BHMT2. Specifically, we sequenced exons, exon-intron splice junctions and the 5'-flanking regions (5'-FRs) of BHMT and BHMT2 using 240 DNA samples from four ethnic groups. Twenty-five single nucleotide polymorphisms (SNPs), including 4 nonsynonymous SNPs, and 39 SNPs, including 4 nonsynonymous, were observed in BHMT and BHMT2, respectively. BHMT wild type (WT) and variant allozymes were expressed in COS-1 cells. Variant allozymes showed no significant differences from WT in levels of enzyme activity or immunoreactive protein, but there were statistically significant differences in apparent K(m) values. Luciferase reporter gene constructs were created for the three most common BHMT 5'-FR haplotypes, and significant variation was observed in the ability of these constructs to drive transcription. Although BHMT2 mRNA has been observed in human liver and kidney, expression of the protein has not been reported. We were unable to express BHMT2 in mammalian cells, and the protein aggregated after bacterial expression. Furthermore, BHMT2 was rapidly degraded in a rabbit reticulocyte lysate, but it could be stabilized by cotransfection of COS-1 cells with BHMT and, after cotransfection, it coprecipitated with BHMT. These studies have defined common genetic variation in BHMT and BHMT2 and functionally characterized BHMT SNPs. They may also help to explain why BHMT2 has not previously been defined functionally.
journal_name
Mol Genet Metabjournal_title
Molecular genetics and metabolismauthors
Li F,Feng Q,Lee C,Wang S,Pelleymounter LL,Moon I,Eckloff BW,Wieben ED,Schaid DJ,Yee V,Weinshilboum RMdoi
10.1016/j.ymgme.2008.03.013subject
Has Abstractpub_date
2008-07-01 00:00:00pages
326-35issue
3eissn
1096-7192issn
1096-7206pii
S1096-7192(08)00081-4journal_volume
94pub_type
杂志文章abstract::Decreased mitochondrial thymidine kinase (TK2) activity is associated with mitochondrial DNA (mtDNA) depletion and respiratory chain dysfunction and is manifested by isolated, fatal skeletal myopathy. Other tissues such as liver, brain, heart, and skin remain unaffected throughout the patients' life. In order to eluci...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Molecular genetics and metabolism
pub_type: 杂志文章,评审
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pub_type: 杂志文章,评审
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journal_title:Molecular genetics and metabolism
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pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章,评审
doi:10.1006/mgme.2000.3003
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journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2014.11.005
更新日期:2015-02-01 00:00:00
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pub_type: 杂志文章,评审
doi:10.1016/j.ymgme.2019.01.015
更新日期:2019-11-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/j.ymgme.2013.02.010
更新日期:2013-05-01 00:00:00
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pub_type: 杂志文章
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journal_title:Molecular genetics and metabolism
pub_type: 杂志文章,评审
doi:10.1006/mgme.1998.2729
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pub_type: 杂志文章
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更新日期:2012-06-01 00:00:00
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journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1006/mgme.1999.2935
更新日期:1999-12-01 00:00:00
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journal_title:Molecular genetics and metabolism
pub_type: 杂志文章,评审
doi:10.1006/mgme.1999.2906
更新日期:1999-10-01 00:00:00
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journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
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journal_title:Molecular genetics and metabolism
pub_type: 杂志文章,评审
doi:10.1016/j.ymgme.2011.06.020
更新日期:2011-11-01 00:00:00
abstract::Gaucher disease (GD) is an autosomal-recessive lysosomal storage disease caused by a deficiency of the enzyme, glucocerebrocidase, resulting in accumulation of lipid-laden storage cells in multiple organs such as bone marrow, liver, spleen, and lungs. Type 1 Gaucher disease is the most common form of this condition in...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
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更新日期:2018-03-01 00:00:00
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journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2015.09.010
更新日期:2015-11-01 00:00:00