Department of Biochemistry and Molecular Genetics, Schools of Medicine and Dentistry, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
J Lipid Res. 2013 Jul;54(7):1744-60. doi: 10.1194/jlr.R037028. Epub 2013 Apr 29.
All-trans-retinoic acid is a biologically active derivative of vitamin A that regulates numerous physiological processes. The concentration of retinoic acid in the cells is tightly regulated, but the exact mechanisms responsible for this regulation are not completely understood, largely because the enzymes involved in the biosynthesis of retinoic acid have not been fully defined. Recent studies using in vitro and in vivo models suggest that several members of the short-chain dehydrogenase/reductase superfamily of proteins are essential for retinoic acid biosynthesis and the maintenance of retinoic acid homeostasis. However, the exact roles of some of these recently identified enzymes are yet to be characterized. The properties of the known contributors to retinoid metabolism have now been better defined and allow for more detailed understanding of their interactions with retinoid-binding proteins and other retinoid enzymes. At the same time, further studies are needed to clarify the interactions between the cytoplasmic and membrane-bound proteins involved in the processing of hydrophobic retinoid metabolites. This review summarizes current knowledge about the roles of various biosynthetic and catabolic enzymes in the regulation of retinoic acid homeostasis and outlines the remaining questions in the field.
全反式视黄酸是维生素 A 的一种生物活性衍生物，可调节多种生理过程。细胞内视黄酸的浓度受到严格调控，但负责这种调控的确切机制尚不完全清楚，这在很大程度上是因为参与视黄酸生物合成的酶尚未完全确定。最近使用体外和体内模型的研究表明，短链脱氢酶/还原酶超家族的几个蛋白成员对视黄酸生物合成和维持视黄酸动态平衡是必不可少的。然而，其中一些最近确定的酶的确切作用仍有待阐明。已知的类视黄醇代谢物贡献者的特性现在已经得到更好的定义，这使得我们能够更详细地了解它们与视黄醇结合蛋白和其他视黄醇酶的相互作用。同时，还需要进一步的研究来阐明参与疏水性视黄醇代谢物加工的细胞质和膜结合蛋白之间的相互作用。本综述总结了目前关于各种生物合成和分解代谢酶在调节视黄酸动态平衡中的作用的知识，并概述了该领域的遗留问题。
