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The storage lesion is exacerbated in some categories of donors as a function of biology (sex, age) 21 , genetic traits 22,23,24,25 , and lifestyle-associated exposures 26 (comprehensively reviewed in 15,21,27,28

This event is followed by the generation of ROS from the oxidation of FADH2 as induced by the demethylase, with consequent oxidation of nearby guanines (8-oxo-Gs) and recruitment of DNA repair enzymes (among which is APE1) that cause single-strand breaks in DNA and enable looping between the enhencer/promoter and the polyadenylation sites of the target genes, with productive transcription 140,141

In this scenario, the traditional concept of a systemic GHK-Cu half life becomes almost irrelevant

(27878767, 34517272) If you dont have access to free valproate levels, then laboratory monitoring may be more accurate with phenobarbital