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Another is chemiexcitation, birthing a reaction product in an electronically excited state rather than exciting from the ground state. Chemiexcited molecules, as in bioluminescence, can release more energy than ATP. Excited states also allow bond rearrangements forbidden in ground states. Molecules with low\u2010lying unoccupied orbitals, abundant in biology, are particularly susceptible. In mammals, chemiexcitation was discovered to transfer energy from excited melanin, neurotransmitters, or hormones to DNA, creating the lethal and carcinogenic cyclobutane pyrimidine dimer. That process was initiated by nitric oxide and superoxide, radicals triggered by ultraviolet light or inflammation. Several poorly understood chronic diseases share two properties: inflammation generates those radicals across the tissue, and cells that die are those containing melanin or neuromelanin. Chemiexcitation may therefore be a pathogenic event in noise\u2010 and drug\u2010induced deafness, Parkinson's disease, and Alzheimer's; it may prevent macular degeneration early in life but turn pathogenic later. Beneficial evolutionary selection for excitable biomolecules may thus have conferred an Achilles heel. This review of recent findings on chemiexcitation in mammalian cells also describes the underlying physics, biochemistry, and potential pathogenesis, with the goal of making this interdisciplinary phenomenon accessible to researchers within each field.<\/jats:p>","DOI":"10.1111\/php.13781","type":"journal-article","created":{"date-parts":[[2023,1,22]],"date-time":"2023-01-22T11:44:04Z","timestamp":1674387844000},"page":"251-276","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Chemiexcitation: Mammalian Photochemistry in the Dark<sup>\u2020<\/sup>"],"prefix":"10.1111","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7437-9373","authenticated-orcid":false,"given":"Douglas E.","family":"Brash","sequence":"first","affiliation":[{"name":"Department of Therapeutic Radiology Yale School of Medicine  New Haven Connecticut"},{"name":"Yale Cancer Center Yale School of Medicine  New Haven Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leticia C. 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