Isolation of the human peroxisomal acyl-CoA oxidase gene: Organization, promoter analysis, and chromosomal localization

Usha Varanasi, Ruiyin Chu, Su Chu, Rafael Espinosa, Michelle M. Lebeau, Janardan K. Reddy*

*Corresponding author for this work

Research output: Contribution to journalArticle

74 Scopus citations

Abstract

Peroxisomal acyl-CoA oxidase (ACOX; EC 1.3.3.6) is the first enzyme of the fatty acid β-oxidation pathway, which catalyzes the desaturation of acyl- CoAs to 2-trans-enoyl-CoAs, and it donates electrons directly to molecular oxygen, thereby producing H2O2. The discovery of carcinogenic peroxisome proliferators, which markedly increase the levels of this H2O2-producing ACOX in rat and mouse liver, generated interest in peroxisomal β-oxidation system genes. The present study deals with the structural organization of human ACOX gene. This gene spans ≃ 33 kb and consists of 14 exons and 13 introns. Primer-extension analysis revealed three principal cap sites, which were mapped at 50, 52, and 53 nt upstream of the initiator methionine codon. The 5' flanking region of the ACOX gene was sequenced up to 500 bp upstream of the cap sites. This promoter region is G+C-rich and contains three copies of the 'GC box' hexanucleotides. Multiple GC boxes are a characteristic feature of the rat ACOX and bifunctional protein genes of the β-oxidation system. A+T-rich TATA-boxlike sequences. TTTATTT and TTATT, have also been identified in this human ACOX gene, but typical CCAAT motifs are absent. This ACOX gene has been mapped to chromosome 17q25 by in situ hybridization, using a biotin-labeled probe.

Original languageEnglish (US)
Pages (from-to)3107-3111
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number8
DOIs
StatePublished - Apr 12 1994

Keywords

  • Zellweger syndrome
  • lipid metabolism
  • peroxisomal β-oxidation

ASJC Scopus subject areas

  • General

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