Pheomelanin
The red-yellow form of melanin that provides less photoprotection than eumelanin and can generate free radicals under UV exposure. Individuals with predominantly pheomelanin (fair skin, red hair) have higher UV sensitivity. The ratio of eumelanin to pheomelanin determines baseline skin photoprotection.
Technical Context
Pheomelanin is a sulphur-containing polymer formed when cysteine conjugates with dopaquinone (diverting the melanogenic pathway from eumelanin production). Its colour ranges from yellow to red. Pheomelanin is less photoprotective than eumelanin and, problematically, can generate reactive oxygen species upon UV exposure (through photosensitisation mechanisms involving the benzothiazine chromophore). Individuals with MC1R loss-of-function variants (common in Celtic populations) produce predominantly pheomelanin, resulting in red hair, fair skin, and increased UV sensitivity and melanoma risk. The eumelanin:pheomelanin ratio is the primary determinant of constitutive photoprotection. Afamelanotide shifts this ratio toward eumelanin by strongly activating MC1R — even in individuals with partial MC1R loss of function, supraphysiological stimulation can increase eumelanin production.