Practice question

Palmitoylation also called S-acylation refers to attachment of 16-carbon saturated palmitate from palmitoyl-CoA to cysteine thiol via thioester bond catalyzed by membrane-bound DHHC motif palmitoyl acyltransferases containing Asp-His-His-Cys catalytic tetrad. Unlike myristoylation or prenylation irreversible thioether amide linkages, thioester is chemically labile and enzymatically reversible, providing dynamic regulation. Removal catalyzed by acyl protein thioesterases APT1 and APT2 and ABHD17 family depalmitoylases in cytosol and lysosomal palmitoyl-protein thioesterase PPT1 involved in Niemann-Pick-like pathology. Cycles of palmitoylation and depalmitoylation control trafficking of PSD-95 to synapses, H-Ras between Golgi and plasma membrane, SNAP25 vesicle fusion, and Galpha subunits signal transduction. Inhibition of depalmitoylation prolongs membrane residency enhancing signaling. Myristoylation via amide to glycine lacks known de-acylase, prenylation thioether also stable, GPI anchor cleaved by phospholipase but not by palmitoyl-protein thioesterase, making depalmitoylation specific for S-palmitoylated proteins regulating membrane association reversibly. 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.