Overview of retinoid metabolism and function

Abstract

Retinoids (vitamin A) are crucial for most forms of life. In chordates, they have important roles in the developing nervous system and notochord and many other embryonic structures, as well as in maintenance of epithelial surfaces, immune competence, and reproduction. The ability of all-trans retinoic acid to regulate expression of several hundred genes through binding to nuclear transcription factors is believed to mediate most of these functions. The role of all-trans retinoic may extend beyond the regulation of gene transcription because a large number of noncoding RNAs also are regulated by retinoic acid. Additionally, extra-nuclear mechanisms of action of retinoids are also being identified. In organisms ranging from prokaryotes to humans, retinal is covalently linked to G protein-coupled transmembrane receptors called opsins. These receptors function as light-driven ion pumps, mediators of phototaxis, or photosensory pigments. In vertebrates phototransduction is initiated by a photochemical reaction where opsin-bound 11-cis-retinal is isomerized to all-trans-retinal. The photosensitive receptor is restored via the retinoid visual cycle. Multiple genes encoding components of this cycle have been identified and linked to many human retinal diseases. Central aspects of vitamin A absorption, enzymatic oxidation of all-trans retinol to all-trans retinal and all-trans retinoic acid, and esterification of all-trans retinol have been clarified. Furthermore, specific binding proteins are involved in several of these enzymatic processes as well as in delivery of all-trans retinoic acid to nuclear receptors. Thus, substantial progress has been made in our understanding of retinoid metabolism and function. This insight has improved our view of retinoids as critical molecules in vision, normal embryonic development, and in control of cellular growth, differentiation, and death throughout life.

The neurobiology of retinoic acid in affective disorders

“…The stored retinyl esters in the liver can be hydrolyzed back to retinol when required, delivered systemically to all cells that require these compounds bound in the plasma to retinol binding protein (RBP). A useful overview of these steps can be found in the Introduction to "Vitamin A in Health and Disease", by Rune Blomhoff (Blomhoff 1994).…”

Expression of key retinoic acid modulating genes suggests active regulation during development and regeneration of the amphibian limb

“…The availability of RA is regulated by production from retinol, catabolism, and binding (reviewed in Blomhoff and Blomhoff, 2006). Dietary retinol is first converted to retinal by alcohol dehydrogenases (ADH), and retinal is then further metabolised to RA by a group of retinal dehydrogenases (Raldh1-3, also known as aldehyde dehydrogenase 1a1-3 or Aldh1a1-3).…”

HPLC/UV quantitation of retinal, retinol, and retinyl esters in serum and tissues

“…Retinoid homeostasis involves balance among multiple retinoids in multiple tissues effected through dietary intake, storage, mobilization, transport, and metabolism (1)(2)(3)(4)(5). Specific binding proteins, enzymes, and receptors control flux through the central pathways of retinoid homeostasis, ultimately to produce retinoic acid, an active form of vitamin A (Figure 1) (6)(7).…”