AKR1C4 Human, His

Aldo-Keto Reductase Family 1 Member C4 Human Recombinant, His Tag

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Cat. No.

BT16609

Source

Escherichia Coli.

Synonyms

Aldo-keto reductase family 1 member C4 (chlordecone reductase 3-alpha hydroxysteroid dehydrogenase type I dihydrodiol dehydrogenase 4), 3-alpha-hydroxysteroid dehydrogenase type I, MGC22581, HAKRA, 3 alpha-hydroxysteroid dehydrogenase/dihydrodiol dehydrogenase 4, CDR, DD4, CHDR, 3-alpha-HSD1, C11.

Appearance

AKR1C4 is supplied as a sterile filtered clear solution.

Purity

Greater than 90.0% as determined by SDS-PAGE.

Usage

Prospec's products are furnished for LABORATORY RESEARCH USE ONLY. The product may not be used as drugs, agricultural or pesticidal products, food additives or household chemicals.

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Description

Enzymatic Functions and Substrate Specificity

AKR1C4 catalyzes bidirectional oxidoreductions of steroids and prostaglandins, with regioselectivity for the 3α-, 17β-, and 20α-positions. Key reactions include:

Reductive Pathways

Steroid Metabolism:
- 5α-pregnane-3,20-dione → 3α-hydroxy-5α-pregnan-20-one (allopregnanolone) .
- 5α-androstane-3,17-dione → 3α-androstanediol (backdoor pathway to DHT) .
Bile Acid Synthesis:
- Reduction of Δ⁴-ketosteroids in bile acid biosynthesis .

Oxidative Pathways

3α-androstanediol → 5α-dihydrotestosterone (DHT) .
Testosterone → Δ⁴-androstene-3,17-dione .

Detoxification

Reduction of chlordecone (a toxic pesticide) to chlordecone alcohol .

Table 1: Substrate Specificity of AKR1C4

Substrate	Reaction	Product	Biological Role
5α-pregnane-3,20-dione	Reduction	Allopregnanolone (neurosteroid)	Neurosteroid synthesis
5α-androstane-3,17-dione	Reduction	3α-androstanediol	Backdoor DHT pathway
3α-androstanediol	Oxidation	5α-DHT	Androgen activation
Chlordecone	Reduction	Chlordecone alcohol	Xenobiotic detoxification

Tissue Expression and Localization

AKR1C4 exhibits liver-specific expression, with minimal activity in other tissues . Its high catalytic efficiency (k<sub>cat</sub>/K<sub>m</sub>) enables robust conversion of 5β-reduced steroids .

Table 2: Tissue Distribution of AKR1C4

Tissue	Expression Level	Key Function
Liver	High	Bile acid synthesis, xenobiotic detox
Prostate	Low	Limited role in androgen metabolism
Brain	Trace	Neurosteroid synthesis (indirect)

Disease Associations

Androgen-Related Disorders: Mutations in AKR1C4 are linked to undervirilized male genitalia in neonates .
Mental Health: AKR1C4 activity correlates with manic/hypomanic irritability in males .
Drug Resistance: Overexpression in ovarian cancer cells may confer cisplatin resistance .

Role in Drug Metabolism

Prodrug Activation: Modulates pharmacokinetics of synthetic steroids and drugs .
Toxicology: Detoxifies chlordecone via NADPH-dependent reduction .

Kinetic Parameters

AKR1C4 demonstrates high catalytic efficiency for 5β-tetrahydrosteroid formation, surpassing other AKR1C isoforms .

Table 3: Kinetic Properties of AKR1C4

Substrate	Reaction	k<sub>cat</sub> (s⁻¹)	K<sub>m</sub> (μM)	k<sub>cat</sub>/K<sub>m</sub> (μM⁻¹ s⁻¹)
5α-pregnane-3,20-dione	Reduction	120	10	12.0
3α-androstanediol	Oxidation	50	5	10.0
Δ⁴-androstene-3,17-dione	Reduction	30	20	1.5

Data adapted from .

Research Applications

AKR1C4 is critical for studying:

Steroid Metabolism: Role in androgen biosynthesis (backdoor pathway) and bile acid synthesis .
Cancer Biology: Biomarker and therapeutic target for castration-resistant prostate cancer (CRPC) .
Toxicology: Mechanisms of chlordecone detoxification and drug interactions .

Product Specs

Introduction

AKR1C4, a member of the aldo/keto reductase superfamily with over 40 known enzymes and proteins, catalyzes the reduction of aldehydes and ketones to their corresponding alcohols using NADH and/or NADPH as cofactors. This enzyme plays a crucial role in detoxifying the organochlorine pesticide chlordecone by converting it to chlordecone alcohol in the liver.

Description

Recombinant human AKR1C4, expressed in E. coli, is a non-glycosylated polypeptide chain comprising 343 amino acids (1-323) with a molecular weight of 39.2 kDa. A 20 amino acid His-Tag is fused to the N-terminus to facilitate purification via proprietary chromatographic techniques.

Physical Appearance

AKR1C4 is provided as a clear, sterile solution after filtration.

Formulation

AKR1C4 protein is supplied at a concentration of 1 mg/ml in a buffer consisting of 20mM Tris-HCl (pH 8), 0.1M NaCl, 1mM DTT, and 20% Glycerol.

Stability

For short-term storage (2-4 weeks), AKR1C4 should be stored at 4°C. For extended storage, it is recommended to freeze the protein at -20°C. The addition of a carrier protein (0.1% HSA or BSA) is advised for long-term storage. Repeated freezing and thawing should be avoided.

Purity

The purity of AKR1C4 is determined to be greater than 90% using SDS-PAGE analysis.

Biological Activity

The specific activity of AKR1C4, defined as the amount of enzyme required to catalyze the oxidation of 1.0 pmole of 1-Acenaphthenol per minute in the presence of NADP at pH 8.8 and 25°C, is greater than 700 pmol/min/µg.

Synonyms

Source

Escherichia Coli.

Amino Acid Sequence

MGSSHHHHHH SSGLVPRGSH MDPKYQRVEL NDGHFMPVLG FGTYAPPEVP RNRAVEVTKL AIEAGFRHID SAYLYNNEEQ VGLAIRSKIA DGSVKREDIF YTSKLWCTFF QPQMVQPALE SSLKKLQLDY VDLYLLHFPM ALKPGETPLP KDENGKVIFD TVDLSATWEV MEKCKDAGLA
KSIGVSNFNC RQLEMILNKP GLKYKPVCNQ VECHPYLNQS KLLDFCKSKD IVLVAHSALG TQRHKLWVDP NSPVLLEDPV LCALAKKHKR TPALIALRYQ LQRGVVVLAK SYNEQRIREN IQVFEFQLTS EDMKVLDGLN RNYRYVVMDF LMDHPDYPFS DEY.

Product Science Overview

Introduction

Aldo-Keto Reductase Family 1 Member C4 (AKR1C4) is a member of the aldo/keto reductase superfamily, which comprises over 40 known enzymes and proteins. These enzymes are involved in the conversion of aldehydes and ketones to their corresponding alcohols by utilizing NADH and/or NADPH as cofactors .

Gene and Protein Structure

The AKR1C4 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 a protein that is primarily expressed in the liver and is involved in various metabolic processes.

Biological Functions

AKR1C4 plays a crucial role in the metabolism of steroid hormones and bile acids. It catalyzes the bioreduction of chlordecone, a toxic organochlorine pesticide, to chlordecone alcohol in the liver. Additionally, it is involved in the transformation of dihydrotestosterone, a potent natural androgen, into 5-alpha-androstan-3-alpha,17-beta-diol, a compound with much lower activity.

Recombinant Protein

The human recombinant AKR1C4 protein, expressed in E. coli and tagged with a His tag, is used in various biochemical assays and research studies. The His tag facilitates the purification of the protein using affinity chromatography.

Clinical Significance

Mutations in the AKR1C4 gene have been associated with disorders such as 46,XY sex reversal 8 and 17 alpha-hydroxylase/17,20-lyase deficiency. These conditions highlight the importance of AKR1C4 in normal physiological processes and its potential as a therapeutic target.

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AKR1C4 Human, His

Description

Enzymatic Functions and Substrate Specificity

Reductive Pathways

Oxidative Pathways

Detoxification

Table 1: Substrate Specificity of AKR1C4

Tissue Expression and Localization

Table 2: Tissue Distribution of AKR1C4

Disease Associations

Role in Drug Metabolism

Kinetic Parameters

Table 3: Kinetic Properties of AKR1C4

Research Applications

Product Specs

Product Science Overview

Quick Inquiry

Category

Service

AKR1C4 Human, His

Description

Enzymatic Functions and Substrate Specificity

Reductive Pathways

Oxidative Pathways

Detoxification

Table 1: Substrate Specificity of AKR1C4

Tissue Expression and Localization

Table 2: Tissue Distribution of AKR1C4

Disease Associations

Role in Drug Metabolism

Kinetic Parameters

Table 3: Kinetic Properties of AKR1C4

Research Applications

Product Specs

Product Science Overview

Quick Inquiry

Category

Service

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