Background:
Paraoxonase (PON) is a family of calcium-dependent hydrolases, which is related to
many diseases. Elucidation of PON physiological roles, active center and all applications in medical fields are
dependent on its substrates.
Objective:
The reports about PON substrates scattered in a long span of period are collected to afford clue for
drug design, diagnosis of PON status and other academic purposes.
Method:
PON substrates from 133 references are classified and compared. Structurally, PON substrates are generally
classified as organic phosphorous esters, lactones and arylesters. Some phosphoramidates, organophosphorous
obidoximes, aryl carboxylic acid amides and special fatty alcohol esters as PON substrates are also included.
Results:
The electron nature, steric hindrance and hydrophilicity of substrate substituents affecting the PON catalytic
ability, binding ability and specificities are discussed. Drugs, prodrugs and naturally endogenous molecules
in life processes activated or inactivate by PON are reviewed. Interestingly, some organophosphate and lactone
substrates are preferably hydrolyzed by one of the PON1R192Q allozymes, and such a substrate is generally essential
for differentiating the three PON1192R phenotypes by using a dual-substrate method. Intricately, some chiral
substrates are hydrolyzed by PON stereoselectively.
Conclusion:
As more substrates are synthesized and characterized, more facts about PON structure and catalytic
properties (including PON active center and catalytic mechanism) will be revealed, and therefore the use of PON
as a drug target or as an accurate disease marker will be achieved.