Abstract
Retinoids carry out essential functions in vertebrate development and vision. Many of the retinoid processing enzymes remain to be identified at the molecular level. To expand the knowledge of retinoid biochemistry in vertebrates, we studied the enzymes involved in plant metabolism of carotenoids, a related group of compounds. We identified a family of vertebrate enzymes that share significant similarity and a putative phytoene desaturase domain with a recently described plant carotenoid isomerase (CRTISO), which isomerizes prolycopene to all-trans-lycopene. Comparison of heterologously expressed mouse and plant enzymes indicates that unlike plant CRTISO, the CRTISO-related mouse enzyme is inactive toward prolycopene. Instead, the CRTISO-related mouse enzyme is a retinol saturase carrying out the saturation of the 13-14 double bond of all-trans-retinol to produce all-trans-13,14-dihydroretinol. The product of mouse retinol saturase (RetSat) has a shifted UV absorbance maximum, lambda(max) = 290 nm, compared with the parent compound, all-trans-retinol (lambda(max) = 325 nm), and its MS analysis (m/z = 288) indicates saturation of a double bond. The product was further identified as all-trans-13,14-dihydroretinol, since its characteristics were identical to those of a synthetic standard. Mouse RetSat is membrane-associated and expressed in many tissues, with the highest levels in liver, kidney, and intestine. All-trans-13,14-dihydroretinol was also detected in several tissues of animals maintained on a normal diet. Thus, saturation of all-trans-retinol to all-trans-13,14-dihydroretinol by RetSat produces a new metabolite of yet unknown biological function.
Highlights
Retinoids are essential for many important biological functions, such as development, immunity, cellular differentiation, and vision of vertebrates
We found proteins that share extensive similarity over the entire length of the protein in several phyla, from bacterial, archaebacterial, and fungal phytoene desaturases to other desaturase and carotenoid isomerase (CRTISO)-like proteins in other plants and higher eukaryotes
A phylogenetic dendogram based on a neighbor-joining algorithm appears to be monophyletic (Fig. 1B) and indicates that the proteins found in vertebrates are related to plant CRTISO (41– 43% conserved substitutions including 25–27% identical residues)
Summary
Retinoids are essential for many important biological functions, such as development, immunity, cellular differentiation, and vision of vertebrates. Retinoids encompassing both natural derivatives of all-trans-retinol and their synthetic analogues exert their functions through several active compounds. In retinal pigment epithelium (RPE), an unidentified enzyme carries out the isomerization of all-trans-retinol either directly or through an ester intermediate to generate 11-cis-retinol, which can be oxidized to 11-cis-retinal, the visual chromophore [4]. In addition to dietary sources, retinoids are derived from the cleavage of C40 provitamin A carotenoids such as ␣- and -carotene and cryptoxanthin to produce retinal, which can be converted to all-trans-retinol. The enzymes involved in the metabolism and physiology of carotenoids in animals await molecular identification
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
