Dietary retinyl esters / β-carotene → retinol (vitamin A) → retinaldehyde (RDH enzymes; reversible) → retinoic acid (RALDH; irreversible). Retinoic acid binds RAR (nuclear receptor) → controls hundreds of genes in differentiation, embryogenesis, vision, immune function. Photoreceptor cycle: 11-cis-retinal + opsin = rhodopsin → light → all-trans-retinal + isomerization back to 11-cis by RPE65 (target of LUXTURNA gene therapy for LCA). Pharmacology: tretinoin (all-trans retinoic acid) = APL (acute promyelocytic leukemia) treatment + topical for acne / photoaging; isotretinoin (13-cis) = severe nodulocystic acne (teratogenic; iPLEDGE program); acitretin = psoriasis. Vitamin A deficiency causes xerophthalmia (preventable blindness in low-resource settings) — major WHO supplementation target.
Organ Systems
integumentary
reproductive
nervous
Pathway Steps
beta-carotene → retinol — via intestinal BCO1 cleavage; alternative source to dietary retinyl esters. BCO1 centrally cleaves provitamin-A carotenoids (β-carotene) to retinal; conversion efficiency varies widely by genotype, so plant carotenoids are a less reliable vitamin-A source than preformed retinyl esters from animal foods.
retinol → retinaldehyde — via RDH (retinol dehydrogenase) — reversible. Retinol dehydrogenase reversibly oxidizes retinol to retinaldehyde, which is also the visual chromophore (11-cis-retinal in rhodopsin) — the basis of vitamin-A-deficiency night blindness.
retinaldehyde → retinoic-acid — via RALDH — irreversible; tissue-restricted (limb buds, immune cells). RALDH irreversibly makes retinoic acid, the active transcriptional ligand, only in restricted tissues (limb buds, immune cells). This irreversible, localized production keeps retinoic-acid signaling tightly compartmentalized and underlies retinoid teratogenicity.
retinoic-acid → rar-rxr-binding — via nuclear receptor binding → RARE-driven transcription. Retinoic acid binds nuclear RAR (with an RXR partner) at RARE elements to drive differentiation genes — exploited by isotretinoin (acne) and by ATRA, which forces differentiation in acute promyelocytic leukemia.