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cDNA cloning and analysis of tissue‐specific expression of mouse peroxisomal straight‐chain acyl‐CoA oxidase

Nöhammer, Christa, El‐Shabrawi, Yosuf, Schauer, Silvia, Hiden, Michaela, Berger, Johannes, Forss‐Petter, Sonja, Winter, Elke, Eferl, Robert, Zechner, Rudolf, Hoefler, Gerald
European journal of biochemistry 2000 v.267 no.4 pp. 1254-1260
acyl coenzyme A, adipose tissue, beta oxidation, brain, chemical structure, complementary DNA, developmental stages, gene expression, heart, humans, hydrogen peroxide, kidneys, liver, messenger RNA, mice, open reading frames, polypeptides, protein synthesis, proteins, rabbits, rats, sequence analysis, suckling
Straight‐chain acyl‐CoA oxidase is the first and rate limiting enzyme in the peroxisomal β‐oxidation pathway catalysing the desaturation of acyl‐CoAs to 2‐trans‐enoyl‐CoAs, thereby producing H2O2. To study peroxisomal β‐oxidation we cloned and characterized the cDNA of mouse peroxisomal acyl‐CoA oxidase. It consists of 3778 bp, including a 1983‐bp ORF encoding a polypeptide of 661 amino‐acid residues. Like the rat and human homologue the C‐terminus contains an SKL motif, an import signal present in several peroxisomal matrix proteins. Sequence analysis revealed high amino‐acid homology with rat (96%) and human (87%) acyl‐CoA oxidase in addition to minor homology (≈ 40%) with other related proteins, such as rabbit trihydroxy‐cholestanoyl‐CoA oxidase, human branched chain acyl‐CoA oxidase and rat trihydroxycoprostanoyl‐CoA oxidase. Acyl‐CoA oxidase mRNA and protein expression were most abundant in liver followed by kidney, brain and adipose tissue. During mouse brain development acyl‐CoA oxidase mRNA expression was highest during the suckling period indicating that peroxisomal β‐oxidation is most critical during this developmental stage. Comparing tissue mRNA levels of peroxisome proliferator‐activated receptor alpha and acyl‐CoA oxidase, we noticed a constant relationship in all tissues investigated, except heart and adipose tissue in which much more, and respectively, much less, peroxisome proliferator‐activated receptor alpha mRNA in proportion to acyl‐CoA oxidase mRNA was found. Our data show that acyl‐CoA oxidase is an evolutionary highly conserved enzyme with a distinct pattern of expression and indicate an important role in lipid metabolism.