Isolation and characterization of cloned cDNAs as encoding human liver chlordecone reductase

Journal Article · Tue Jan 30 00:00:00 EST 1990 · Biochemistry; (USA)

DOI:https://doi.org/10.1021/bi00456a034· OSTI ID:6710157

Winters, C J; Molowa, D T; Guzelian, P S ^[1]

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1. Medical College of Virginia, Richmond (USA)

Chlordecone (Kepone), a toxic organochlorine pesticide, undergoes bioreduction to chlorodecone alcohol in human liver. This reaction is controlled by a cytosolic enzyme, chlordecone reductase (CDR), which may be of the aldo-keto reductase family of xenobiotic metabolizing enzymes. To further investigate the primary structure and expression of CDR, the authors screened a library of human liver cDNAs cloned in the expression vector {lambda}gt11 and isolated an 800 bp cDNA that directed synthesis of a fusion protein recognized by polyclonal anti-CDR antibodies. Using this cDNA as a probe, they screened two human liver cDNA libraries and found several 1.2-kb cDNAs which would code for polypeptide with 308 residues (35.8 kDa). However, a similar full-length cDNA, possibly the transcript of a pseudogene, contained an in-frame nonsense codon. The deduced protein sequence of CDR showed 65% similarity to the primary structure of human liver aldehyde reductase and 66% similarity to the inferred protein sequence of rat lens aldose reductase. A search of GenBank revealed significant nucleotide similarity to a cDNA coding for bovine lung prostaglandin f synthase and to a partial cDNA coding for frog lens {rho}-crystallin. RNA from adult but not fetal human liver, and from the human hepatoma cell-line Hep G2, contained major (1.6 kb) and minor (2.8 kb) species hybridizable to a CDR cDNA. The relative amounts of these RNAs varied markedly among nine subjects. From this initial description of the nucleotide sequence for a human carbonyl reductase, they conclude that CDR and several related enzymes are part of a novel multigene family involved in the metabolism of such xenobiotics as chlordecone and possibly endogenous substrates.

• OSTI ID: 6710157
• Journal Information: Biochemistry; (USA), Vol. 29:4; ISSN 0006-2960
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
KEPONE
METABOLISM
MIXED-FUNCTION OXIDASES
DNA SEQUENCING
OXIDOREDUCTASES
MOLECULAR STRUCTURE
XENOBIOTICS
DNA HYBRIDIZATION
DNA-CLONING
LIVER
MAN
MESSENGER-RNA
PESTICIDES
ANIMALS
BODY
CLONING
DIGESTIVE SYSTEM
ENZYMES
GLANDS
HYBRIDIZATION
INSECTICIDES
MAMMALS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANS
OXYGENASES
PRIMATES
RNA
STRUCTURAL CHEMICAL ANALYSIS
VERTEBRATES
550200* - Biochemistry
560300 - Chemicals Metabolism & Toxicology