Abstract
Cellular retinoic acid binding proteins (CRABPs) bind all-trans-retinoic acid (atRA) tightly. This study aimed to determine whether atRA is channeled directly to cytochrome P450 (CYP) CYP26B1 by CRABPs, and whether CRABPs interact directly with CYP26B1. atRA bound to CRABPs (holo-CRABP) was efficiently metabolized by CYP26B1. Isotope dilution experiments showed that delivery of atRA to CYP26B1 in solution was similar with or without CRABP. Holo-CRABPs had higher affinity for CYP26B1 than free atRA, but both apo-CRABPs inhibited the formation of 4-OH-RA by CYP26B1. Similar protein-protein interactions between soluble binding proteins and CYPs may be important for other lipophilic CYP substrates.
Keywords:
binding proteins; cytochrome P450; retinoic acid; substrate channeling.
© 2016 Federation of European Biochemical Societies.
Publication types
-
Letter
-
Research Support, Non-U.S. Gov't
-
Research Support, N.I.H., Extramural
MeSH terms
-
Amino Acid Sequence / genetics
-
Carrier Proteins / genetics
-
Carrier Proteins / metabolism
-
Endoplasmic Reticulum / genetics
-
Endoplasmic Reticulum / metabolism
-
Gene Expression Regulation
-
Humans
-
Kinetics
-
Protein Interaction Maps / genetics*
-
Receptors, Retinoic Acid / genetics
-
Receptors, Retinoic Acid / metabolism*
-
Retinoic Acid 4-Hydroxylase / chemistry
-
Retinoic Acid 4-Hydroxylase / genetics
-
Retinoic Acid 4-Hydroxylase / metabolism*
-
Retinol-Binding Proteins, Cellular / genetics
-
Retinol-Binding Proteins, Cellular / metabolism
-
Substrate Specificity
-
Tretinoin / chemistry
-
Tretinoin / metabolism*
Substances
-
Carrier Proteins
-
Receptors, Retinoic Acid
-
Retinol-Binding Proteins, Cellular
-
retinoic acid binding protein I, cellular
-
retinoic acid binding protein II, cellular
-
Tretinoin
-
CYP26B1 protein, human
-
Retinoic Acid 4-Hydroxylase