CYP26C1 Is a Hydroxylase of Multiple Active Retinoids and Interacts with Cellular Retinoic Acid Binding Proteins

Molecular Pharmacology
Guo ZhongNina Isoherranen

Abstract

The clearance of retinoic acid (RA) and its metabolites is believed to be regulated by the CYP26 enzymes, but the specific roles of CYP26A1, CYP26B1, and CYP26C1 in clearing active vitamin A metabolites have not been defined. The goal of this study was to establish the substrate specificity of CYP26C1, and determine whether CYP26C1 interacts with cellular retinoic acid binding proteins (CRABPs). CYP26C1 was found to effectively metabolize all-trans retinoic acid (atRA), 9-cis-retinoic acid (9-cis-RA), 13-cis-retinoic acid, and 4-oxo-atRA with the highest intrinsic clearance toward 9-cis-RA. In comparison with CYP26A1 and CYP26B1, CYP26C1 resulted in a different metabolite profile for retinoids, suggesting differences in the active-site structure of CYP26C1 compared with other CYP26s. Homology modeling of CYP26C1 suggested that this is attributable to the distinct binding orientation of retinoids within the CYP26C1 active site. In comparison with other CYP26 family members, CYP26C1 was up to 10-fold more efficient in clearing 4-oxo-atRA (intrinsic clearance 153 μl/min/pmol) than CYP26A1 and CYP26B1, suggesting that CYP26C1 may be important in clearing this active retinoid. In support of this, CRABPs delivered 4-oxo-atRA and atRA...Continue Reading

References

Nov 30, 1990·Biochemical and Biophysical Research Communications·A AströmJ J Voorhees
Aug 17, 1993·Biochemical Pharmacology·J C Kraft, M R Juchau
Jan 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·G AllenbyP Chambon
Jan 1, 1997·Methods in Enzymology·D EisenbergJ U Bowie
Jan 31, 2003·Proteins·Simon C LovellDavid C Richardson
Oct 9, 2003·The Journal of Biological Chemistry·Mohammed TaimiMartin Petkovich
Jul 21, 2004·Journal of Computational Chemistry·Felix AutenriethZaida Luthey-Schulten
Oct 8, 2005·Journal of Computational Chemistry·David Van Der SpoelHerman J C Berendsen
Sep 4, 2007·Journal of Cystic Fibrosis : Official Journal of the European Cystic Fibrosis Society·Asim MaqboolVirginia A Stallings
Nov 11, 2008·Biochemical Pharmacology·Justin D LutzNina Isoherranen
Jun 13, 2009·Expert Opinion on Drug Metabolism & Toxicology·Jayne E Thatcher, Nina Isoherranen
Apr 27, 2010·Annual Review of Nutrition·Noa Noy
Jun 2, 2010·Biochemical Pharmacology·Jayne E ThatcherNina Isoherranen
Jun 1, 1995·Toxicology in Vitro : an International Journal Published in Association with BIBRA·K Herrmann
Jul 30, 2010·The Journal of Biological Chemistry·Natalia MastC David Stout
Nov 16, 2010·Annual Review of Pathology·Xiao-Han Tang, Lorraine J Gudas
Dec 1, 2010·Proceedings of the National Academy of Sciences of the United States of America·Maureen A KaneJoseph L Napoli
Apr 2, 2011·Clinical and Experimental Dermatology·A H Schmitt-HoffmannJ Maares
Apr 28, 2011·Molecular Pharmacology·Jayne E ThatcherNina Isoherranen
May 31, 2011·Biochimica Et Biophysica Acta·Joseph L Napoli
Sep 13, 2011·Journal of Pharmacological and Toxicological Methods·Christian HelvigMartin Petkovich
Oct 11, 2011·Biochimica Et Biophysica Acta·Maureen A Kane
Oct 15, 2011·Journal of Computational Chemistry·Kiumars ShahrokhThomas E Cheatham
Oct 25, 2011·Biochemical Pharmacology·Ariel R TopletzNina Isoherranen
Dec 24, 2011·Journal of Lipid Research·Samuel L M ArnoldNina Isoherranen
Oct 17, 2012·The Journal of Biological Chemistry·Jakob A ShimshoniNina Isoherranen
Mar 13, 2014·Proceedings of the National Academy of Sciences of the United States of America·Brian C MonkRobert M Stroud
Nov 18, 2014·Journal of Chemical Theory and Computation·Jacob D DurrantRommie E Amaro
Jun 10, 2015·Antimicrobial Agents and Chemotherapy·Alia A SagatovaJoel D A Tyndall
Aug 4, 2015·Advances in Pharmacology·Faith StevisonNina Isoherranen
Mar 5, 2016·The Journal of Pharmacology and Experimental Therapeutics·Robert S FotiDominique Douguet
Nov 11, 2016·Sub-cellular Biochemistry·Natalia Y Kedishvili

❮ Previous
Next ❯

Citations

May 9, 2019·Genesis : the Journal of Genetics and Development·Suya Wang, Alexander R Moise
Aug 17, 2019·Pharmacology & Therapeutics·Nina Isoherranen, Guo Zhong
Oct 20, 2019·Pharmacology & Therapeutics·Suya WangAlexander R Moise
Jan 25, 2020·Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids·Ioan Ovidiu SirbuAlexander Radu Moise
Mar 17, 2021·JCI Insight·Ni YangD Brian Foster
Jun 24, 2021·Drug Discovery Today·David MachalzGerhard Wolber
Sep 19, 2021·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Aditi Dubey, Jean-Pierre Saint-Jeannet

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.