cDNA cloning and expression of the human hepatic bile acid-binding protein. A member of the monomeric reductase gene family.

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Stolz A, Hammond L, Lou H, Takikawa H, Ronk M, Shively JE

cDNA cloning and expression of the human hepatic bile acid-binding protein. A member of the monomeric reductase gene family.

J Biol Chem. 1993 May 15;268(14):10448-57.

PubMed ID

8486699 [ View in PubMed

]

Abstract

In human liver, we previously identified one isoform of dihydrodiol dehydrogenase activity that expresses high affinity bile acid binding (HBAB) with minimal 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD) activity for bile acids. This protein may assist in the rapid intracellular transport of bile acids from the sinusoidal to the canalicular pole of the cell. We now report the cDNA cloning and bacterial expression of this novel, multifunctional protein. A 1252-base pair HBAB cDNA was cloned from a HepG2 lambda GT11 library using a rat hepatic bile acid binder cDNA probe. Bacterial expressed recombinant HBAB oxidized racemic trans dihydrodiol benzene (0.455 mumol NADPH/mg/min) with minimal 3 alpha-HSD activity for bile acids (< 0.003 mumol NADPH/mg/min). Lithocholic acid and chenodeoxycholic acid dissociation constants as determined by displacement of the fluorescent probe, bis-1-anilino-8 sulfonate, were higher than those previously reported for the native protein (1 microM versus 10 nM). Significant amino acid sequence homology was found with the human chlordecone reductase, bovine prostaglandin F synthetase, and rat hepatic-3 alpha-HSD suggesting, that HBAB is also a member of the recently identified, monomeric oxidoreductase gene family. Future studies will define the physiologic significance of this novel, multifunctional protein in bile acid transport and xenobiotic metabolism.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Chenodeoxycholic acid	Aldo-keto reductase family 1 member C2	Protein	Humans	Unknown	Substrate	Details

Polypeptides

Name	UniProt ID
Aldo-keto reductase family 1 member C1	Q04828	Details
Aldo-keto reductase family 1 member C2	P52895	Details