Cloning and functional characterization of ACAD-9, a novel member of human acyl-CoA dehydrogenase family.
Acyl-CoA dehydrogenases (ACADs) are a family of mitochondrial enzymes catalyzing the initial rate-limiting step in the beta-oxidation of fatty acyl-CoA. The reaction provides main source of energy for human heart and skeletal muscle. Eight human ACADs have been described. Deficiency of these enzymes, especially very long-chain acyl-CoA dehydrogenase (VLCAD), usually leads to severe human organic diseases, such as sudden death in infancy, infantile cardiomyopathy (CM), hypoketotic hypoglycemia, or hepatic dysfunction. By large-scale random sequencing, we identified a novel homolog of ACADs from human dendritic cell (DC) cDNA library. It contains an open reading frame (ORF) of 1866bp, which encodes a 621 amino acid protein. It shares approximately 47% amino acid identity and 65% similarity with human VLCAD. So, the novel molecule is named as acyl-CoA dehydrogenase-9 (ACAD-9), the ninth member of ACADs. The new gene consists of 18 exons and 17 introns, and is mapped to chromosome 3q26. It contains the two signatures shared by all members of the ACADs. ACAD-9 mRNA is ubiquitously expressed in most normal human tissues and cancer cell lines with high level of expression in heart, skeletal muscles, brain, kidney, and liver. Enzymatic assay proved that the recombinant ACAD-9 protein has the dehydrogenase activity on palmitoyl-coenzyme A (C16:0) and stearoyl-coenzyme A (C18:0). Our results indicate that ACAD-9 is a novel member of ACADs.
D042964:Acyl-CoA Dehydrogenase; D044942:Acyl-CoA Dehydrogenase, Long-Chain / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D044944:Acyl-CoA Dehydrogenases; D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D017124:Conserved Sequence; D018076:DNA, Complementary / Q000737:chemistry / Q000302:isolation & purification; D005260:Female; D018922:HL-60 Cells; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000201:enzymology*; D009928:Organ Specificity; D011247:Pregnancy; D011994:Recombinant Proteins / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D018076:DNA, Complementary; D011994:Recombinant Proteins; D044944:Acyl-CoA Dehydrogenases; C122081:ACAD8 protein, human; D042964:Acyl-CoA Dehydrogenase; D044942:Acyl-CoA Dehydrogenase, Long-Chain; C467805:ACADVL protein, human