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134.
Betaine homocysteine S-methyltransferase: just a regulator of homocysteine metabolism? 总被引:1,自引:0,他引:1
Betaine homocysteine methyltransferase (BHMT), a Zn2+-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.
Received 26 May 2006; received after revision 3 July 2006; accepted 24 August 2006 相似文献
135.
Valdar W Solberg LC Gauguier D Burnett S Klenerman P Cookson WO Taylor MS Rawlins JN Mott R Flint J 《Nature genetics》2006,38(8):879-887
Difficulties in fine-mapping quantitative trait loci (QTLs) are a major impediment to progress in the molecular dissection of complex traits in mice. Here we show that genome-wide high-resolution mapping of multiple phenotypes can be achieved using a stock of genetically heterogeneous mice. We developed a conservative and robust bootstrap analysis to map 843 QTLs with an average 95% confidence interval of 2.8 Mb. The QTLs contribute to variation in 97 traits, including models of human disease (asthma, type 2 diabetes mellitus, obesity and anxiety) as well as immunological, biochemical and hematological phenotypes. The genetic architecture of almost all phenotypes was complex, with many loci each contributing a small proportion to the total variance. Our data set, freely available at http://gscan.well.ox.ac.uk, provides an entry point to the functional characterization of genes involved in many complex traits. 相似文献
136.
Epigenetic asymmetry of imprinted genes in plant gametes 总被引:12,自引:0,他引:12
Gutiérrez-Marcos JF Costa LM Dal Prà M Scholten S Kranz E Perez P Dickinson HG 《Nature genetics》2006,38(8):876-878
Plant imprinted genes show parent-of-origin expression in seed endosperm, but little is known about the nature of parental imprints in gametes before fertilization. We show here that single differentially methylated regions (DMRs) correlate with allele-specific expression of two maternally expressed genes in the seed and that one DMR is differentially methylated between gametes. Thus, plants seem to have developed similar strategies as mammals to epigenetically mark imprinted genes. 相似文献
137.
Horvath A Boikos S Giatzakis C Robinson-White A Groussin L Griffin KJ Stein E Levine E Delimpasi G Hsiao HP Keil M Heyerdahl S Matyakhina L Libè R Fratticci A Kirschner LS Cramer K Gaillard RC Bertagna X Carney JA Bertherat J Bossis I Stratakis CA 《Nature genetics》2006,38(7):794-800
Phosphodiesterases (PDEs) regulate cyclic nucleotide levels. Increased cyclic AMP (cAMP) signaling has been associated with PRKAR1A or GNAS mutations and leads to adrenocortical tumors and Cushing syndrome. We investigated the genetic source of Cushing syndrome in individuals with adrenocortical hyperplasia that was not caused by known defects. We performed genome-wide SNP genotyping, including the adrenocortical tumor DNA. The region with the highest probability to harbor a susceptibility gene by loss of heterozygosity (LOH) and other analyses was 2q31-2q35. We identified mutations disrupting the expression of the PDE11A isoform-4 gene (PDE11A) in three kindreds. Tumor tissues showed 2q31-2q35 LOH, decreased protein expression and high cyclic nucleotide levels and cAMP-responsive element binding protein (CREB) phosphorylation. PDE11A codes for a dual-specificity PDE that is expressed in adrenal cortex and is partially inhibited by tadalafil and other PDE inhibitors; its germline inactivation is associated with adrenocortical hyperplasia, suggesting another means by which dysregulation of cAMP signaling causes endocrine tumors. 相似文献
138.
139.
Gilbert SL Zhang L Forster ML Anderson JR Iwase T Soliven B Donahue LR Sweet HO Bronson RT Davisson MT Wollmann RL Lahn BT 《Nature genetics》2006,38(2):245-250
Hypertonia, which results from motor pathway defects in the central nervous system (CNS), is observed in numerous neurological conditions, including cerebral palsy, stroke, spinal cord injury, stiff-person syndrome, spastic paraplegia, dystonia and Parkinson disease. Mice with mutation in the hypertonic (hyrt) gene exhibit severe hypertonia as their primary symptom. Here we show that hyrt mutant mice have much lower levels of gamma-aminobutyric acid type A (GABA(A)) receptors in their CNS, particularly the lower motor neurons, than do wild-type mice, indicating that the hypertonicity of the mutants is likely to be caused by deficits in GABA-mediated motor neuron inhibition. We cloned the responsible gene, trafficking protein, kinesin binding 1 (Trak1), and showed that its protein product interacts with GABA(A) receptors. Our data implicate Trak1 as a crucial regulator of GABA(A) receptor homeostasis and underscore the importance of hyrt mice as a model for studying the molecular etiology of hypertonia associated with human neurological diseases. 相似文献
140.
Lubelski J Rink R Khusainov R Moll GN Kuipers OP 《Cellular and molecular life sciences : CMLS》2008,65(3):455-476
This review discusses the state-of-the-art in molecular research on the most prominent and widely applied lantibiotic, i.e., nisin. The developments in understanding its complex biosynthesis and mode of action are highlighted. Moreover, novel applications
arising from engineering either nisin itself, or from the construction of totally novel dehydrated and/or lanthionine-containing
peptides with desired bioactivities are described. Several challenges still exist in understanding the immunity system and
the unique multiple reactions occurring on a single substrate molecule, carried out by the dehydratase NisB and the cyclization
enzyme NisC. The recent elucidation of the 3-D structure of NisC forms the exciting beginning of further 3-D-structure determinations
of the other biosynthetic enzymes, transporters and immunity proteins. Advances in achieving in vitro activities of lanthionine-forming enzymes will greatly enhance our understanding of the molecular characteristics of the
biosynthesis process, opening up new avenues for developing unique and novel biocatalytic processes.
Received 9 April 2007; received after revision 31 August 2007; accepted 28 September 2007 相似文献