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Related Pathways Retinol Metabolism RAR Activation View All Pathways

Synonyms: all-trans retinol dehydrogenase, MDR, microsomal retinol dehydrogenase, RDH, retinal reductase, retinene reductase, retinol (vitamin A1) dehydrogenase, Retinol dehydrogenase, retinol:NAD oxidoreductase

Retinol Metabolism in Human Liver

Retinol (Vitamin A) (all-trans retinol) and its metabolites, all-trans- and cis-Retinoic acid and 11-cis-Retinal, are involved in processes such as vision, reproduction, growth development and immune function. Cis retinal (11-cis-retinal) acts as a chromophore for visual pigments in rod and cone photoreceptor cells. All-trans and 9-cis retinoic acids act through at least six distinct ligand-dependent transcription factors.

Vitamin A exists in the diet primarily as long-chain fatty acid retinyl esters along with small amounts of retinol and retinoic acid. Dietary retinyl esters are hydrolyzed to retinol in the intestinal lumen by pancreatic triglyceride lipase and intestinal brush border associated phospholipase B. Free retinol is absorbed by enterocytes, re-esterified with long-chain fatty acids by lecithin:retinol acyltransferase (LRAT), incorporated into chylomicrons and secreted into the lymphatic system. Endothelial cell-bound lipoprotein lipase hydrolyses chylomicron triglycerides resulting in the formation of chylomicron remnants that still bind retinyl ester. These chylomicron remnants are incorporated into liver parenchymal cells by low density lipoprotein (LDL) receptor-mediated endocytosis. The retinyl esters are hydrolyzed to retinol by neutral and acid retinyl ester hydrolases (REH), including carboxylesterase ES-10 (EC 3.1.1.1), an ER associated acid retinyl ester hydrolase. ER associated retinol is bound to retinol-binding protein (RBP). Retinol-RBP complexes can be secreted into the circulation or the retinol can be metabolized within the parenchymal cells. Excess retinol is transported to stellate cells (Ito cells) for storage as retinyl esters. Mobilization of stellate retinyl esters requires hydrolysis by neutral and/or acidic REH.

Retinol (all-trans retinol) is converted to retinal (all-trans retinal) by retinol dehydrogenases (EC 1.1.1.105). All-trans retinal is converted into 11-cis-retinal by retinal isomerase (EC 5.2.1.3) or into all-trans retinoic acid (RA) by retinal dehydrogenases (EC 1.2.1.36). The retinal dehydrogenase isoforms, RALDH1 and RALDH2, are expressed in stellate (Ito) cells and hepatocytes, respectively. The conversion of retinal into retinoic acid is typically a rate-limiting step for retinoic acid accumulation.