Varanasi U, Chu R, Chu S, Espinosa R, LeBeau M M, Reddy J K
Department of Pathology, Northwestern University Medical School, Chicago, IL 60611.
Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3107-11. doi: 10.1073/pnas.91.8.3107.
Peroxisomal acyl-CoA oxidase (ACOX; EC 1.3.3.6) is the first enzyme of the fatty acid beta-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 beta-oxidation system genes. The present study deals with the structural organization of human ACOX gene. This gene spans approximately 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 beta-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 biotinlabeled probe.
过氧化物酶体酰基辅酶A氧化酶（ACOX；EC 1.3.3.6）是脂肪酸β-氧化途径的首个酶，它催化酰基辅酶A脱氢生成2-反式烯酰辅酶A，并将电子直接传递给分子氧，从而产生过氧化氢。致癌性过氧化物酶体增殖剂的发现，使大鼠和小鼠肝脏中这种产生过氧化氢的ACOX水平显著升高，引发了人们对过氧化物酶体β-氧化系统基因的兴趣。本研究探讨了人类ACOX基因的结构组织。该基因跨度约33 kb，由14个外显子和13个内含子组成。引物延伸分析揭示了三个主要的帽位点，它们位于起始甲硫氨酸密码子上游50、52和53个核苷酸处。对ACOX基因的5'侧翼区域进行测序，直至帽位点上游500 bp处。该启动子区域富含G + C，并包含三个“GC盒”六核苷酸拷贝。多个GC盒是大鼠ACOX和β-氧化系统双功能蛋白基因的特征。在该人类ACOX基因中还鉴定出富含A + T的类似TATA盒的序列TTTATTT和TTATT，但不存在典型的CCAAT基序。使用生物素标记的探针，通过原位杂交将该ACOX基因定位到染色体17q25上。
