Abstract
A hypothesis is presented that ester-based lipids possess an intrinsic reactivity towards some non-lipid constituents of cellular membranes. The term 'intrinsic lipidation' is used to describe the acyl transfer process from a membrane lipid as donor to a suitable membrane-embedded acceptor (doi: 10.1002/bies.201900147). The intrinsic lipidation of small organic molecules and peptides has been demonstrated in model membranes in conditions where acyl transfer can only occur by direct transfer from the lipid. In addition, the lipidation of some drugs, such as propranolol, has been demonstrated in vivo and yields product profiles that reflect the acyl composition of the host cellular membrane. There is good evidence that some proteins are also lipidated by direct transfer from membrane lipids. The toxic effects of intrinsic lipidation are hypothesized to include a route by which nucleation can occur during the formation of amyloid fibrils. Lipases and deacylases are proposed as enzymes that protect cells against the effects of intrinsic lipidation.
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