Practice question

Lipid modifications differ in chemistry of linkage and reversibility. N-myristoylation forms amide bond between myristate and N-terminal glycine co-translationally irreversible, palmitoylation forms thioester between 16-carbon palmitate and cysteine thiol reversibly cleaved by acyl protein thioesterases, GPI anchoring forms amide between ethanolamine phosphate and C-terminus plus glycosidic linkages to inositol phospholipid. Prenylation, either farnesylation 15-carbon or geranylgeranylation 20-carbon, occurs at C-terminal CAAX motif where X determines farnesyl vs geranylgeranyl transferase specificity. Farnesyltransferase and geranylgeranyltransferase I catalyze attack of cysteine thiolate on isoprenoid pyrophosphate forming thioether bond C-S-C that is stable, irreversible and requires subsequent proteolysis of AAX residues and carboxymethylation for full membrane targeting. Ras, Rho, Rab and nuclear lamins use prenylation for membrane anchoring necessary for signaling, cytoskeletal organization and nuclear envelope assembly. Thioester thioether distinction separates palmitoylation from prenylation chemistry and membrane affinity. 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.