ArticleJournal of lipid research2013
Lipoxygenase pathways in Homo neanderthalensis: functional comparison with Homo sapiens isoforms.
Article in Journal of lipid research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 14 citations in OpenAlex.
- A Multistep Computational Approach to Achieve a Complete Human 5-Lipoxygenase Structure and Provide a Pharmacophore Model for Further Drug Design.Molecular informatics · 2026Article
- Iron metabolism and ferroptosis: druggable targets to delay the progression of lupus nephritis.American journal of physiology. Renal physiology · 2026Review
- Functional consequence of Iron dyshomeostasis and ferroptosis in systemic lupus erythematosus and lupus nephritis.Clinical immunology (Orlando, Fla.) · 2024Review
- The Reaction Specificity of Mammalian ALOX15 Orthologs is Changed During Late Primate Evolution and These Alterations Might Offer Evolutionary Advantages for Hominidae.Frontiers in cell and developmental biology · 2022Article
- Identification of the first congenital ichthyosis case caused by a homozygous deletion in theFrontiers in genetics · 2022Article
- Evolutionary alteration of ALOX15 specificity optimizes the biosynthesis of antiinflammatory and proresolving lipoxins.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Review
- Evolutionary aspects of lipoxygenases and genetic diversity of human leukotriene signaling.Progress in lipid research · 2015Review
- Functional characterization of genetic enzyme variations in human lipoxygenases.Redox biology · 2013Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lipoxygenases (LOX) have been implicated in biosynthesis of pro- and anti-inflammatory mediators, and a previous report suggested compromised leukotriene signaling in H. neanderthalensis. To search for corresponding differences in leukotriene biosynthesis, we screened the Neandertal genome for LOX genes and found that, as modern humans, this archaic hominid contains six LOX genes (nALOX15, nALOX12, nALOX5, nALOX15B, nALOX12B, and nALOXE3) and one pseudogene. In the Neandertal genome, 60-75% of the amino acids of the different human LOX isoforms have been identified, and the degree of identity varies between 96 and 99%. Most functional amino acids (iron ligands, specificity determinants, calcium and ATP-binding sites, membrane-binding determinants, and phosphorylation sites) are well conserved in the Neandertal LOX isoforms, and expression of selected neandertalized human LOX mutants revealed no major functional defects. However, in nALOX12 and nALOXE3, two premature stop codons were found, leading to inactive enzyme species. These data suggest that ALOX15, ALOX5, ALOX15B, and ALOX12B should have been present as functional enzymes in H. neanderthalensis and that in contrast to lower nonhuman primates (M. mulatta) and other mammals (mice, rats), this ancient hominid expressed a 15-lipoxygenating ALOX15. Expression of ALOXE3 and ALOX12 was compromised, which might have caused problems in epidermal differentiation.
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