PON1 Human, HEK
Description
Introduction to PON1 Human, HEK
PON1 Human, HEK refers to recombinant human paraoxonase-1 (PON1) produced in human embryonic kidney (HEK) cells. This enzyme is a glycosylated, 346-amino acid polypeptide with a molecular mass of 39.0 kDa, fused to a 6-amino acid His-tag for purification . PON1 is a high-density lipoprotein (HDL)-associated lactonase and esterase that detoxifies organophosphates (OPs), nerve agents (e.g., sarin, soman), and oxidized lipid metabolites, playing a critical role in cardiovascular and neuroprotective pathways .
Production in HEK Cells
HEK-produced PON1 retains native glycosylation patterns, which may influence immunogenicity and therapeutic efficacy in humans . Bacterial systems lack post-translational modifications, simplifying production but potentially altering function .
Substrate Specificity
PON1 Human, HEK hydrolyzes:
Catalytic Efficiency
| Variant | Substrate | Catalytic Efficiency (Vmax/Km) | Reference |
|---|---|---|---|
| Q192 | Paraoxon | Moderate | |
| R192 | Chlorpyrifos oxon | Higher affinity, lower Vmax | |
| K192 | Diazoxon, CPO, PO | Enhanced activity (engineered) |
The Q192R polymorphism influences OP detoxification, with Q192 showing higher activity against nerve agents .
Organophosphate Detoxification
Recombinant PON1 variants (e.g., K192) protect PON1 knockout mice from lethal OP exposures . HEK-produced PON1, though less studied than E. coli-derived versions, offers a platform for clinical trials due to human-compatible glycosylation .
Cardiovascular and Neuroprotective Roles
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Atherosclerosis: Hydrolyzes oxidized lipid metabolites, reducing inflammation .
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Parkinson’s Disease: HDL-associated PON1 activity correlates with disease progression .
Cancer Research
PON1 overexpression in lung cancer cells (e.g., H460, H1299) promotes proliferation, bypasses senescence, and suppresses apoptosis via p53 modulation . This highlights its dual role in disease pathology and therapeutic targeting.
Comparative Analysis of PON1 Sources
Research Challenges and Future Directions
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Glycosylation Impact: Studies on HEK-produced PON1’s immunogenicity in humans are lacking.
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Cancer Therapeutics: PON1’s pro-survival role in tumors necessitates targeted inhibition strategies .
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OP Exposure Treatments: Engineering HEK-produced PON1 for enhanced catalytic efficiency (e.g., K192 variant) could improve therapeutic efficacy .
Product Specs
Serum paraoxonase/arylesterase 1, Serum aryldialkylphosphatase 1, Aromatic esterase 1, A-esterase 1 , Serum aryldialkylphosphatase 1, paraoxonase 1, K-45, ESA, PON, MVCD5
HEK293 Cells.
LFRNHQSSYQ TRLNALREVQ PVELPNCNLV KGIETGSEDL EILPNGLAFI SSGLKYPGIK SFNPNSPGKI LLMDLNEEDP TVLELGITGS KFDVSSFNPH GISTFTDEDN AMYLLVVNHP DAKSTVELFK FQEEEKSLLH LKTIRHKLLP NLNDIVAVGP EHFYGTNDHY FLDPYLQSWE MYLGLAWSYV VYYSPSEVRV VAEGFDFANG INISPDGKYV YIAELLAHKI HVYEKHANWT LTPLKSLDFN TLVDNISVDP ETGDLWVGCH PNGMKIFFYD SENPPASEVL RIQNILTEEP KVTQVYAENG TVLQGSTVAS VYKGKLLIGT VFHKALYCEL HHHHHH
Product Science Overview
Paraoxonase-1 is produced in the liver and distributed through the bloodstream, where it interacts with HDL. The recombinant form of PON1, produced in Human Embryonic Kidney (HEK) cells, is a single, glycosylated polypeptide chain consisting of 346 amino acids with a molecular mass of approximately 39.0 kDa . This recombinant enzyme is fused to a 6-amino acid His-tag at the C-terminus and is purified using proprietary chromatographic techniques .
PON1 is known for its ability to hydrolyze a wide range of substrates, including cyclic carbonates, lactones, and nerve gases . It requires activation by PPAR-gamma, which leads to its synthesis and release from liver tissue, ultimately contributing to the reduction of atherosclerosis . The enzyme’s anti-atherosclerotic properties are attributed to its role in metabolizing inflammatory lipid peroxides .
Recombinant PON1 is used extensively in laboratory research, particularly in studies related to cardiovascular diseases and toxicology . It is supplied as a sterile, filtered, colorless solution containing 20% glycerol and phosphate-buffered saline (pH 7.4) . For optimal stability, it should be stored at 4°C if used within 2-4 weeks or frozen at -20°C for longer periods . To prevent degradation, it is recommended to avoid multiple freeze-thaw cycles and to add a carrier protein for long-term storage .
