AKR1C3 Human, His
Description
Introduction and Overview
AKR1C3 Human, His refers to the recombinant human aldo-keto reductase 1C3 (AKR1C3) enzyme produced in E. coli with a His-tag fusion for purification. This enzyme belongs to the AKR superfamily, catalyzing the reduction of aldehydes, ketones, and steroids using NADPH/NADH as cofactors. Its roles include hormone metabolism, prostaglandin synthesis, and implications in cancer progression .
Molecular Properties
| Property | Value | Source |
|---|---|---|
| Molecular Weight | 39 kDa | |
| Amino Acids | 343 residues (1–323 a.a.) | |
| His-Tag | 20 amino acid N-terminal tag | |
| Purity | >95% (SDS-PAGE confirmed) | |
| Specific Activity | >1,000 pmol/min/μg (NADPH) |
Hormone Metabolism
AKR1C3 regulates steroid hormones and prostaglandins:
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Androgen Synthesis: Converts Δ⁴-androstenedione to testosterone, a critical step in prostate cancer progression .
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Estrogen/Progesterone Metabolism: Modulates 17β-estradiol and progesterone ratios, influencing breast cancer biology .
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Prostaglandin F2α (PGF2α): Oxidizes PGF2α to PGD2, affecting inflammation and tumor microenvironments .
Cancer-Associated Pathways
Cancer Progression
AKR1C3 is overexpressed in hormone-dependent cancers:
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Prostate Cancer: Elevated in metastatic cases; correlates with Gleason score and enzalutamide resistance .
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Breast Cancer: Modulates estrogen receptor signaling and PGJ2 production .
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Hepatocellular Carcinoma (HCC): Activates MEK/ERK and NF-κB pathways, promoting survival .
Therapeutic Targeting
Inhibitors like BAY1128688 suppress AKR1C3 activity, reducing androsterone (a biomarker for inhibition) without disrupting ovarian function in premenopausal women .
Enzymatic Assays
AKR1C3 activity is quantified via:
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NADPH Oxidation: Measured at 25°C (e.g., 1 μmol NADPH/min) .
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Substrate Specificity: Catalyzes Δ⁴-androstenedione → testosterone (K<sub>cat</sub>/K<sub>M</sub> = 0.23 μM<sup>-1</sup>) .
Tissue Distribution
AKR1C3 immunoreactivity is detected in:
Biomarkers and Inhibitors
Product Specs
Product Science Overview
Aldo-Keto Reductase Family 1 Member C3 (AKR1C3), also known as 17β-hydroxysteroid dehydrogenase type 5 (17β-HSD5) or 3α-hydroxysteroid dehydrogenase type 2 (3α-HSD2), is a crucial enzyme in the aldo-keto reductase superfamily. This family comprises over 40 known enzymes and proteins that catalyze the conversion of aldehydes and ketones to their corresponding alcohols using NADH and/or NADPH as cofactors .
The AKR1C3 gene is located on chromosome 10p15-p14 and shares high sequence identity with three other gene members clustered in the same region . The gene encodes multiple transcript variants, resulting in different isoforms of the protein . The recombinant form of AKR1C3, tagged with a His tag, is often used in research to facilitate purification and detection.
AKR1C3 plays a significant role in steroid metabolism. It catalyzes the reduction of prostaglandin D2 (PGD2), prostaglandin H2 (PGH2), and phenanthrenequinone (PQ), and the oxidation of 9α,11β-PGF2 to PGD2 . Additionally, it is involved in the metabolism of estrogen and progesterone . This enzyme’s activity is crucial for various physiological processes, including the development of allergic diseases such as asthma and the regulation of cell growth and differentiation .
AKR1C3 is overexpressed in prostate cancer (PCa) and is associated with the development of castration-resistant prostate cancer (CRPC) . Its overexpression may serve as a promising biomarker for prostate cancer progression . The enzyme’s role in converting adrenal androgen dehydroepiandrosterone (DHEA) into high-affinity ligands for the androgen receptor (testosterone and dihydrotestosterone) underscores its importance in steroidogenesis .
