Pheomelanin provides a useful biological function in organisms
Whether pheomelanin provides a net useful biological function remains contested, as studies show it can act as an antioxidant or protect cellular components, while other research links its synthesis and prooxidant properties to increased oxidative stress, DNA damage, and melanoma risk.
The retrieved literature presents a dichotomy regarding pheomelanin. Some studies (e.g., [3], [9], [11]) highlight its antioxidant capabilities or protective precursor functions against lipid peroxidation. Conversely, major lines of research (e.g., [0], [7], [10]) emphasize its propensity to generate reactive oxygen species, act as a prooxidant in the presence of iron, and drive phototoxic DNA damage linked to melanoma. Because of these well-documented conflicting biological outcomes—photoprotection/antioxidant activity versus phototoxicity/oxidative stress—the overall balance is CONTESTED.
Huijuan Bi, Jonas Tranell, Dawn C. Harper, Weifeng Lin, Jingyi Li, A. R. Hellström, M. Larsson, C. Rubin, Chao Wang, S. Sayyab, S. Kerje, B. Bed’hom, D. Gourichon, S. Ito, K. Wakamatsu, M. Tixier-Boichard, M. Marks, D. Globisch, L. Andersson. A frame-shift mutation in COMTD1 is associated with impaired pheomelanin pigmentation in chicken. 2023. https://doi.org/10.1371/journal.pgen.1010724
Paper 3 suggests that the metabolic pathways and associated enzymes involved in pheomelanin production play a protective role for melanocytes against oxidative stress.
Ann M. Morgan, Jennifer Lo, David E. Fisher. How does pheomelanin synthesis contribute to melanomagenesis?. 2013. https://doi.org/10.1002/bies.201300020
Paper 0 links pheomelanin synthesis to increased oxidative stress and DNA damage, contributing to a higher risk of melanoma in redheads.
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E S Krol, D C Liebler. Photoprotective actions of natural and synthetic melanins.. 1998. https://doi.org/10.1021/tx980114c
Paper 9 demonstrates that pheomelanin can exert antioxidant effects against UV-induced lipid peroxidation under certain conditions.
S Schmitz, P D Thomas, T M Allen, M J Poznansky, K Jimbow. Dual role of melanins and melanin precursors as photoprotective and phototoxic agents: inhibition of ultraviolet radiation-induced lipid peroxidation.. 1995. https://doi.org/10.1111/j.1751-1097.1995.tb09883.x
Paper 11 indicates that pheomelanin precursors can reduce lipid peroxidation and help protect against harmful UV radiation effects.
K Jimbow. Current update and trends in melanin pigmentation and melanin biology.. 1995. https://doi.org/10.2302/kjm.44.9
Paper 7 notes that while pheomelanin has some antioxidant properties, it can become a prooxidant in the presence of iron upon UV exposure.
Dan-Ning Hu, Howard E Savage, Joan E Roberts. Uveal melanocytes, ocular pigment epithelium, and Müller cells in culture: in vitro toxicology.. 2002. https://doi.org/10.1080/10915810290169891
Paper 10 discusses how pheomelanin can exhibit phototoxic effects and act as a prooxidant as its properties change.
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