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Review
, 4 (5), 356-71

The Adverse Effects of Alcohol on Vitamin A Metabolism

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Review

The Adverse Effects of Alcohol on Vitamin A Metabolism

Robin D Clugston et al. Nutrients.

Abstract

The objective of this review is to explore the relationship between alcohol and the metabolism of the essential micronutrient, vitamin A; as well as the impact this interaction has on alcohol-induced disease in adults. Depleted hepatic vitamin A content has been reported in human alcoholics, an observation that has been confirmed in animal models of chronic alcohol consumption. Indeed, alcohol consumption has been associated with declines in hepatic levels of retinol (vitamin A), as well as retinyl ester and retinoic acid; collectively referred to as retinoids. Through the use of animal models, the complex interplay between alcohol metabolism and vitamin A homeostasis has been studied; the reviewed research supports the notion that chronic alcohol consumption precipitates a decline in hepatic retinoid levels through increased breakdown, as well as increased export to extra-hepatic tissues. While the precise biochemical mechanisms governing alcohol's effect remain to be elucidated, its profound effect on hepatic retinoid status is irrefutable. In addition to a review of the literature related to studies on tissue retinoid levels and the metabolic interactions between alcohol and retinoids, the significance of altered hepatic retinoid metabolism in the context of alcoholic liver disease is also considered.

Keywords: alcohol dehydrogenase; aldehyde dehydrogenase; cytochrome P450; ethanol; hepatic stellate cell; hepatocyte; retinoic acid; retinol; retinyl ester.

Figures

Figure 1
Figure 1
Biochemical parallels in the metabolism of ethanol and retinol. The conversion of ethanol to acetaldehyde is mediated by different processes within the cell; this reaction can be catalyzed by alcohol dehydrogenase, CYP2E1, and to a lesser extent, catalase. The conversion of the primary alcohol, retinol, to retinaldehyde can also be catalyzed by alcohol dehydrogenase subtypes, as well as specific retinol dehydrogenases. In both cases, the subsequent oxidation of the aldehyde to a carboxylic acid is mediated by aldehyde dehydrogenases. Within the liver, the synthesis of retinyl ester is catalyzed by lecithin: retinol acyltransferase (LRAT); the molecular identity of enzymes which synthesize fatty acid ethyl esters are currently unknown.
Figure 2
Figure 2
A simplified overview of retinoid metabolism in a hypothetical cell. This scheme reflects retinoid metabolism in a hypothetical cell. The reader should note that these processes do not typically occur within all cells in vivo, but have been grouped here for simplicity. Similarly, multiple isoforms exist for many of the binding proteins and enzymes presented below; for a complete review of retinoid metabolism, please refer to the recent review by D’Ambrosio et al. [55]. In the cytoplasm, retinol is bound to a cellular retinol-binding protein (CRBP), from this point there are three possible pathways for retinol to take. First, retinol can be transferred to retinol-binding protein (RBP), which itself is bound to transthyretin (TTR), and secreted into the circulation. Second, it can be esterified into retinyl ester by lecithin:retinol acyltransferase (LRAT), and stored in cytoplasmic lipid droplets. Third, it can be metabolized into retinaldehyde and subsequently converted into retinoic acid. Retinoic acid may be bound by a cellular retinoic acid binding protein (CRABP), which can direct it toward the nucleus where it can signal through the nuclear transcription factors retinoic acid receptor (RAR) and retinoid X receptor (RXR), or it can be directed toward catabolism into polar metabolites by various members of the cytochrome P450 family (CYP). Catalytic enzymes are shown in red text; binding proteins are in blue text. ADH: alcohol dehydrogenase; RALDH: retinaldehyde dehydrogenase; RDH: retinol dehydrogenase; REH: retinyl ester hydrolase.

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