Which lipid-linked protein modification is not reversible?
Lipid modifications vary in stability and enzymatic reversibility enabling dynamic membrane association. Palmitoylation S-acylation via DHHC family palmitoyl acyltransferases forming thioester linkage can be removed by acyl protein thioesterases APT1, APT2 and ABHD17 family allowing cycles of membrane binding and cytosolic redistribution crucial for neuronal signaling proteins like PSD-95 and H-Ras. Prenylation thioether linkage is irreversible chemically stable requiring proteolysis for reversal; however protease cleavage of prenylated C-terminus does not regenerate unmodified cysteine. GPI anchoring cleavable by phospholipases but attachment considered stable. N-myristoylation via amide linkage between 14-carbon myristoyl-CoA and N-terminal glycine catalyzed by N-myristoyltransferase after methionine removal is co-translational and generally irreversible because no de-myristoylase known in cytosol, anchor persists lifetime of protein determining permanent membrane targeting. Some reports of lysine myristoylation reversible but glycine myristoylation is essentially non-reversible distinguishing it from palmitoylation that provides regulatory switch for membrane affinity and subcellular trafficking. Such detailed mechanistic insight is frequently examined in competitive tests including NEET, CUET, CSIR-NET and GATE where transporter classification, energetics and disease linkage are integrated into problem-solving questions.
Ref: Resh, Nat Chem Biol 2013, Reversibility of lipid modifications; Chamberlain & Shipston, Physiol Rev 2015.