array(1) { [0]=> object(AppBundle\Entity\geneTOpubmed)#305 (6) { ["id":"AppBundle\Entity\geneTOpubmed":private]=> int(273) ["geneNihId":"AppBundle\Entity\geneTOpubmed":private]=> int(641371) ["pubmedNihId":"AppBundle\Entity\geneTOpubmed":private]=> int(16940157) ["title":"AppBundle\Entity\geneTOpubmed":private]=> string(174) "Analysis of the mouse and human acyl-CoA thioesterase (ACOT) gene clusters shows that convergent, functional evolution results in a reduced number of human peroxisomal ACOTs." ["urltitle":"AppBundle\Entity\geneTOpubmed":private]=> string(170) "analysis-of-the-mouse-and-human-acyl-coa-thioesterase-acot-gene-clusters-shows-that-convergent-functional-evolution-results-in-a-reduced-number-of-human-peroxisomal-acots" ["content":"AppBundle\Entity\geneTOpubmed":private]=> string(10895) " 16940157 2006 09 18 2012 02 15
1530-6860 20 11 2006 Sep FASEB journal : official publication of the Federation of American Societies for Experimental Biology FASEB J. Analysis of the mouse and human acyl-CoA thioesterase (ACOT) gene clusters shows that convergent, functional evolution results in a reduced number of human peroxisomal ACOTs. 1855-64 The maintenance of cellular levels of free fatty acids and acyl-CoAs, the activated form of free fatty acids, is extremely important, as imbalances in lipid metabolism have serious consequences for human health. Acyl-coenzyme A (CoA) thioesterases (ACOTs) hydrolyze acyl-CoAs to the free fatty acid and CoASH, and thereby have the potential to regulate intracellular levels of these compounds. We previously identified and characterized a mouse ACOT gene cluster comprised of six genes that apparently arose by gene duplications encoding acyl-CoA thioesterases with localizations in cytosol (ACOT1), mitochondria (ACOT2), and peroxisomes (ACOT3-6). However, the corresponding human gene cluster contains only three genes (ACOT1, ACOT2, and ACOT4) coding for full-length thioesterase proteins, of which only one is peroxisomal (ACOT4). We therefore set out to characterize the human genes, and we show here that the human ACOT4 protein catalyzes the activities of three mouse peroxisomal ACOTs (ACOT3, 4, and 5), being active on succinyl-CoA and medium to long chain acyl-CoAs, while ACOT1 and ACOT2 carry out similar functions to the corresponding mouse genes. These data strongly suggest that the human ACOT4 gene has acquired the functions of three mouse genes by a functional convergent evolution that also provides an explanation for the unexpectedly low number of human genes. Hunt Mary C MC Karolinska Institutet, Department of Laboratory Medicine, Division of Clinical Chemistry C1-74, Karolinska University Hospital at Huddinge, Stockhold SE-141 86, Sweden. mary.hunt@ki.se Rautanen Anna A Westin Maria A K MA Svensson L Thomas LT Alexson Stefan E H SE eng GENBANK DQ082754 DQ082755 DQ082756 RefSeq NM_152331 Journal Article Research Support, Non-U.S. Gov't
United States FASEB J 8804484 0892-6638 0 DNA Primers EC 3.1.2.- Thiolester Hydrolases EC 3.1.2.2 ACOT2 protein, human EC 3.1.2.2 ACOT4 protein, human EC 3.1.2.2 Palmitoyl-CoA Hydrolase IM Amino Acid Sequence Animals Base Sequence Cloning, Molecular DNA Primers Evolution, Molecular Humans Mice Molecular Sequence Data Multigene Family Open Reading Frames Palmitoyl-CoA Hydrolase genetics Peroxisomes enzymology Reverse Transcriptase Polymerase Chain Reaction Sequence Alignment Sequence Homology, Amino Acid Thiolester Hydrolases genetics Transcription, Genetic
2006 8 31 9 0 2006 9 19 9 0 2006 8 31 9 0 ppublish 16940157 20/11/1855 10.1096/fj.06-6042com
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