cDNA cloning and analysis of tissueâspecific expression of mouse peroxisomal straightâchain acylâCoA oxidase

Nöhammer, Christa; ElâShabrawi, Yosuf; Schauer, Silvia; Hiden, Michaela; Berger, Johannes; ForssâPetter, Sonja; Budde-Winter, Elke; Eferl, Robert; Zechner, Rudolf; Hoefler, Gerald

cDNA cloning and analysis of tissueâspecific expression of mouse peroxisomal straightâchain acylâCoA oxidase

2000

Straightâchain acylâCoA oxidase is the first and rate limiting enzyme in the peroxisomal βâoxidation pathway catalysing the desaturation of acylâCoAs to 2âtransâenoylâCoAs, thereby producing H2O2. To study peroxisomal βâoxidation we cloned and characterized the cDNA of mouse peroxisomal acylâCoA oxidase. It consists of 3778âbp, including a 1983âbp ORF encoding a polypeptide of 661 aminoâacid residues. Like the rat and human homologue the Câterminus contains an SKL motif, an import signal present in several peroxisomal matrix proteins. Sequence analysis revealed high aminoâacid homology with rat (96%) and human (87%) acylâCoA oxidase in addition to minor homology (≈â40%) with other related proteins, such as rabbit trihydroxyâcholestanoylâCoA oxidase, human branched chain acylâCoA oxidase and rat trihydroxycoprostanoylâCoA oxidase. AcylâCoA oxidase mRNA and protein expression were most abundant in liver followed by kidney, brain and adipose tissue. During mouse brain development acylâCoA oxidase mRNA expression was highest during the suckling period indicating that peroxisomal βâoxidation is most critical during this developmental stage. Comparing tissue mRNA levels of peroxisome proliferatorâactivated receptor alpha and acylâCoA oxidase, we noticed a constant relationship in all tissues investigated, except heart and adipose tissue in which much more, and respectively, much less, peroxisome proliferatorâactivated receptor alpha mRNA in proportion to acylâCoA oxidase mRNA was found. Our data show that acylâCoA oxidase is an evolutionary highly conserved enzyme with a distinct pattern of expression and indicate an important role in lipid metabolism.

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