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Studies on human serum paraoxonase/arylesterase
1Department of Pharmacology, Medical School, University of Michigan, Ann Arbor 48109-0572.
Chemico-Biological Interactions
|June 1, 1993
Summary
Human serum paraoxonase/arylesterase exists in two forms, A and B, with distinct activities. These allozymes differ due to a single nucleotide change, impacting paraoxonase activity and salt stimulation.
Area of Science:
- Biochemistry
- Genetics
- Enzymology
Background:
- Human serum paraoxonase/arylesterase (PON1) protein and DNA sequences are known.
- Evidence suggests two genetically determined allozymic forms (A and B) with paraoxonase and arylesterase activities.
Purpose of the Study:
- To elucidate the structural basis for differing allozyme properties.
- To investigate the effect of phosphatidylcholine and serum lipoprotein binding on enzyme activity.
Main Methods:
- DNA sequencing to identify genetic variations.
- Enzyme kinetics studies with and without phosphatidylcholine.
- Analysis of enzyme binding to high-density lipoproteins (HDL).
Main Results:
- A single nucleotide difference at position 572 (codon 191) distinguishes A (glutamine) and B (arginine) allozymes.
- The B allozyme exhibits higher paraoxonase activity and greater stimulation by NaCl.
- Phosphatidylcholine increases the maximum velocity but not Km, while serum binding to HDL (apo A-1) is observed but its functional significance is unclear.
Conclusions:
- Genetic variation significantly impacts human serum paraoxonase/arylesterase activity.
- Phosphatidylcholine modulates enzyme kinetics, suggesting a role in activity regulation.
- The physiological role remains undefined, but organophosphate hydrolysis may confer protection.