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Article Abstract

The human genome involves six functional arachidonic acid (AA) lipoxygenase () genes, and the corresponding enzymes (ALOX15, ALOX15B, ALOX12, ALOX12B, ALOXE3, ALOX5) have been implicated in cell differentiations and in the pathogenesis of inflammatory, hyperproliferative, metabolic, and neurological disorders. Humans express two different AA 15-lipoxygenating ALOX isoforms, and these enzymes are called ALOX15 (15-LOX1) and ALOX15B (15-LOX2). Chromosomal localization, sequence alignments, and comparison of the enzyme properties suggest that pig and mouse ALOX15 orthologs (leukocyte-type 12-LOX) on the one hand and rabbit and human ALOX15 orthologs on the other (reticulocyte-type 15-LOX1) belong to the same enzyme family despite their different reaction specificities with AA as a substrate. In contrast, human ALOX12 (platelet-type 12-LOX), as well as pig and mouse ALOX15 (leukocyte-type 12-LOX), belong to different enzyme families, although they exhibit a similar reaction specificity with AA as a substrate. The complex multiplicity of mammalian ALOX isoforms and the controversial enzyme nomenclatures are highly confusing and prompted us to summarize the current knowledge on the biological functions, enzymatic properties, and allosteric regulation mechanisms of mammalian ALOX15, ALOX15B, and ALOX12 orthologs that belong to three different enzyme sub-families.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11593649PMC
http://dx.doi.org/10.3390/ijms252212058DOI Listing

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Background: Mammalian arachidonic acid lipoxygenases (ALOXs) have previously been implicated in the pathogenesis of inflammatory disease, and pro- as well as anti-inflammatory activities have been reported. The human genome involves six functional ALOX genes and each of them encodes for a functionally distinct enzyme. ALOX15 is one of these isoforms and the majority of mammalian ALOX15 orthologs including mouse Alox15 convert arachidonic acid to its 12-hydroperoxy derivative.

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Arachidonic acid lipoxygenases (ALOXs) play important roles in cell differentiation and in the pathogenesis of cardiovascular, hyperproliferative, neurodegenerative, and metabolic diseases. The human genome involves six intact ALOX genes and knockout studies of the corresponding mouse orthologs indicated that the coding multiplicity of ALOX isoforms is not an indication for functional redundancy. Despite their evolutionary relatedness human and mouse ALOX15 and ALOX15B orthologs exhibit different catalytic properties.

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Article Synopsis
  • The human genome consists of six Arachidonic Acid (AA) lipoxygenase genes, with enzymes that play roles in various disorders, including inflammation and metabolic issues.
  • Humans have two main AA 15-lipoxygenating enzymes, ALOX15 and ALOX15B, which have been linked to different reaction pathways despite being part of the same enzyme family.
  • The diversity of mammalian ALOX isoforms and differing enzyme names can be confusing, highlighting the need to clarify their biological functions and regulatory mechanisms.
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