**2. Retinoic acid is a vitamin A derivative**

atRA is synthesized in two steps from vitamin A (all-*trans*-retinol). The first step produces all-*trans*-retinaldehyde from all-*trans*-retinol through the action of cytosolic or membrane bound alcohol dehydrogenases (ADH). The second, irreversible, step in atRA synthesis involves the oxidization of all-*trans*-retinaldehyde to atRA through the actions of the cytosolic retinaldehyde dehydrogenases (RALDH1, RALDH2, RALDH3; a.k.a. Aldh1α1, Aldh1α2, Aldh1α3) [16, 17]. Tissue concentrations of atRA are regulated by the activities of these synthesizing enzymes, as well as the atRA-metabolizing enzyme CYP26, a member of the cytochrome P450 family [17]. Cyp1B1 may also contribute to atRA synthesis in the chick embryo [18] via synthesis of all-*trans*-retinaldehyde and atRA from all-*trans*-retinol. Furthermore, the rate of these reactions is regulated by the availability of the substrates, the accessibility of the enzymes to their substrates, and the catalytic activity of the enzymes [19]. Once synthesized, atRA can act within its own cell of synthesis (autocrine signaling) or be transported to nearby cells (paracrine signaling) and bind with nuclear retinoic acid receptor complexes to directly control the transcriptional activity of more than 100 target genes [20].
