Martinez Agosto Julian A, McCabe Edward R B
Department of Pediatrics, David Geffen School of Medicine at UCLA, USA.
Mol Genet Metab. 2006 Aug;88(4):334-45. doi: 10.1016/j.ymgme.2006.01.002. Epub 2006 Mar 20.
Glycerol kinase (GK) is an enzyme that catalyzes the formation of glycerol 3-phosphate from ATP and glycerol, the rate-limiting step in glycerol utilization. We analyzed the genome of the model organism Drosophila melanogaster and identified five GK orthologs, including two loci with sequence homology to the mammalian Xp21 GK protein. Using a combination of sequence analysis and evolutionary comparisons of orthologs between species, we characterized functional domains in the protein required for GK activity. Our findings include additional conserved domains that suggest novel nuclear and mitochondrial functions for glycerol kinase in apoptosis and transcriptional regulation. Investigation of GK function in Drosophila will inform us about the role of this enzyme in development and will provide us with a tool to examine genetic modifiers of human metabolic disorders.
甘油激酶(GK)是一种催化由ATP和甘油形成3-磷酸甘油的酶,这是甘油利用中的限速步骤。我们分析了模式生物黑腹果蝇的基因组,鉴定出五个GK直系同源物,包括两个与哺乳动物Xp21 GK蛋白具有序列同源性的基因座。通过结合序列分析和物种间直系同源物的进化比较,我们表征了GK活性所需蛋白质中的功能域。我们的发现包括额外的保守结构域,这表明甘油激酶在细胞凋亡和转录调控中具有新的核功能和线粒体功能。对果蝇中GK功能的研究将使我们了解这种酶在发育中的作用,并为我们提供一个工具来研究人类代谢紊乱的遗传修饰因子。