Regulation of Hepatic Retinol Metabolism: Perspectives from Studies on Vitamin A Status

A. Catharine Ross, Reza Zolfaghari

Research output: Contribution to journalArticle

88 Scopus citations

Abstract

Liver vitamin A (retinol) is obtained from several sources and is subject to multiple fates. Lecithin: retinol acyltransferase (LRAT), a microsomal enzyme present in liver and several other retinol-metabolizing tissues, esterifies retinol that is associated with a cellular retinol-binding protein, CRBP or CRBP-II. Recent research has shown that LRAT mRNA expression and enzyme activity are regulated in a tissue-specific manner. In vitamin A-deficient liver, both LRAT mRNA and activity are significantly down-regulated as well as rapidly induced after the administration of vitamin A or its principal hormonal metabolite, retinoic acid (RA). In long-term feeding studies and the metabolic steady state, liver LRAT is expressed dose-dependently across a wide range of dietary vitamin A. Additionally, an RA-inducible cytochrome P450, P450RAI or CYP26, is down-regulated in liver during vitamin A deficiency and up-regulated dose-dependently by dietary vitamin A and exogenous RA. Based on these results, we propose that LRAT and CYP26 serve as two molecular mechanisms, coordinately regulated by all-trans-RA, to control the availability of retinol and RA, respectively. The LRAT reaction, besides providing a readily retrievable storage form of vitamin A, may regulate the availability of retinol to other pathways, while the CYP26 reaction may serve to prevent a detrimental "overshoot" of RA concentration. Moreover, retinoid metabolism in the liver is likely to be closely integrated with that in peripheral tissues through the rapid interorgan transfer and recycling of retinoids, affecting the whole-body economy of vitamin A.

Original languageEnglish (US)
Pages (from-to)269S-275S
JournalJournal of Nutrition
Volume134
Issue number1
DOIs
StatePublished - Jan 2004

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

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