Mammalian metabolism of β-carotene: gaps in knowledge

Abstract

β-carotene is the most abundant provitamin A carotenoid in human diet and tissues. It exerts a number of beneficial functions in mammals, including humans, owing to its ability to generate vitamin A as well as to emerging crucial signaling functions of its metabolites. Even though β-carotene is generally considered a safer form of vitamin A due to its highly regulated intestinal absorption, detrimental effects have also been ascribed to its intake, at least under specific circumstances. A better understanding of the metabolism of β-carotene is still needed to unequivocally discriminate the conditions under which it may exert beneficial or detrimental effects on human health and thus to enable the formulation of dietary recommendations adequate for different groups of individuals and populations worldwide. Here we provide a general overview of the metabolism of this vitamin A precursor in mammals with the aim of identifying the gaps in knowledge that call for immediate attention. We highlight the main questions that remain to be answered in regards to the cleavage, uptake, extracellular and intracellular transport of β-carotene as well as the interactions between the metabolism of β-carotene and that of other macronutrients such as lipids.

Figure 1

Summary of β-carotene metabolism. Symmetric oxidative cleavage of β-carotene at the 15,15′ double bond by the enzyme β-carotene-15,15′-oxygenase (CMOI or BCMO1 or BCO1) generates two molecules of retinaldehyde. Retinaldehyde can be oxidized into retinoic acid by members of the aldehyde dehydrogenase 1 family of enzymes (ALDH 1 or RALDH). Further oxidation of retinoic acid by enzymes that belong to the cytochrome P450 (CYP) 26 family converts retinoic acid into more polar compounds, including 4-oxo retinoic acid, which are believed to be transcriptionally inactive. Alternatively, different forms of alcohol dehydrogenase (ADH) from the MDR superfamily, and a variety of retinol dehydrogenases (RDH) from the SDR superfamily can reduce retinaldehyde to retinol, which can be further esterified into retinyl esters by the enzyme lecithin:retinol acyltransferase (LRAT). In addition, apocarotenals can be generated from β-carotene. The cleavage at the 9′,10′ double bond is catalyzed by β-carotene 9′,10′-oxygenase 2 (CMOII or BCDO2 or BCO2) and leads to the formation of β-apo-10′-carotenal (indicated by an asterisk) and β-ionone. Asymmetric cleavage at other double bonds may occur non-enzymatically or may be enzyme catalyzed. Some of the potential apocarotenals generated by asymmetric cleavage of β-carotene are depicted in the figure. The dashed arrow indicates that apocarotenals can be ultimately converted into one molecule of retinaldehyde. The mechanism of this conversion has not been completely elucidated. A chain shorthening mechanism has been proposed. However, recent reports from von Lintig’s and Harrion’s groups suggested that apocarotenoids can be cleaved by CMOI to yield retinaldehyde.