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Because cleavage of the MEP side-group may take place in the presence of the specific esterase(s) in epidermal/dermal layers of the skin 111113 and not in the bloodstream that would alter the mechanism of action, especially the estrogen binding characteristics

doi: 10.1002/jcb.30195 86 van SwelmRPLWetzelsJFMSwinkelsDW

Tawada C, Kanoh H, Nakamura M, Mizutani Y, Fujisawa T, Banno Y, et al

Sequence: trans-3-hexenoyl-Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-NH

In such scenarios, directional selection is more effectively reflected by a diminished level of genetic variation, rather than the traditional Hardy-Weinberg equilibrium (HWE) expectations [65]

Thornburgh, S., & Gaskins, A