IRREVERSIBLE INHIBITOR

Diisopropyl Phosphate Fluoridate (DIPF)

DIPF irreversible inactivates the enzyme acetyl choline esterase, a serine esterase that catalyses the hydrolysis of acetylcholine.NOTE: Acetylcholine is a neurotransmitter. It transmits nerve impulse across the synapses between certain types of nerve cells. ↓Acetylcholine is degraded by a post synaptic membrane-bound enzyme before the arrival of the next nerve impulse. ↓The products acetate and choline are transported back into the pre-synaptic terminal for recycling to acetylcholine. ↓The inactivation of acetylcholine esterase by DIPF prevents the otherwise rapid hydrolysis of the acetylcholine releases by a nerve impulse and thereby interferes with the regular sequence of nerve impulse. ↓Failure of transmission of nerve impulse propels results in paralysis and thus death by suffocation. ↓Hence, DIPF was used as nerve gases in military.

DIPF combines with the hydroxyl group of an essential serine residue at the active site of acetylcholine esterase to form a catalytically inactive derivative. Once this derivative is formed, the enzyme molecules can no longer function. ch6-ufig18

DIFP has been found to inhibit a whole class of enzymes; many of them are capable of catalysing hydrolysis of peptide on ester linkages. They include not only acetylcholine esterase but also trypsin chymotrypsin, elastase, phosphoglucose esterase, and cocoonase (an enzyme secreted by silkworm larvae to hydrolyse the silk fibres of the cocoon, allowing the larva to escape). All the DIFP-inhibited enzymes have an essential serine residue in their active site, which participates in their catalytic activity.

There is a useful side of DIFP. It has led to the development of malathion and other insecticides that are relatively non-toxic for people and animals. Malathion is inactive by itself and degraded by higher animals into product that are harmless to them, but it is converted by enzymes of insects into an active inhibitor of their acetylcholine esterase.


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