Mammalian Carotenoid-oxygenases: Key players for carotenoid function and homeostasis

doi:10.1016/j.bbalip.2011.04.010

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids

Volume 1821, Issue 1, January 2012, Pages 78-87

https://doi.org/10.1016/j.bbalip.2011.04.010 Get rights and content

Abstract

Humans depend on a dietary intake of lipids to maintain optimal health. Among various classes of dietary lipids, the physiological importance of carotenoids is still controversially discussed. On one hand, it is well established that carotenoids, such as β,β-carotene, are a major source for vitamin A that plays critical roles for vision and many aspects of cell physiology. On the other hand, large clinical trials have failed to show clear health benefits of carotenoids supplementation and even suggest adverse health effects in individuals at risk of disease. In recent years, key molecular players for carotenoid metabolism have been identified, including an evolutionarily well conserved family of carotenoid-oxygenases. Studies in knockout mouse models for these enzymes revealed that carotenoid metabolism is a highly regulated process and that this regulation already takes place at the level of intestinal absorption. These studies also provided evidence that β,β-carotene conversion can influence retinoid-dependent processes in the mouse embryo and in adult tissues. Moreover, these analyses provide an explanation for adverse health effects of carotenoids by showing that a pathological accumulation of these compounds can induce oxidative stress in mitochondria and cell signaling pathways related to disease. Advancing knowledge about carotenoid metabolism will contribute to a better understanding of the biochemical and physiological roles of these important micronutrients in health and disease. This article is part of a Special Issue entitled Retinoid and Lipid Metabolism.

Section snippets

Out of the wild green yonder: carotenoid cleaving enzymes

Vitamin A was recognized as an essential factor in food a century ago. Early research suggested that certain yellow plant pigments had the same activity as vitamin A. This phenomenon was explained in 1930 by Moore [11], who described a conversion of β,β-carotene into vitamin A in the small intestine of the rat, thus providing the first evidence that a plant-derived carotenoid is the direct precursor of retinoids. Karrer [12] elucidated the structure of β,β-carotene and proposed a central

Mammalian genomes encode three different CCE family members

In mammals, three different members of the CCE family have been molecularly identified and biochemically characterized. RPE65 is expressed in the retinal pigment epithelium of the eyes and localizes to the endoplasmatic reticulum. The critical role of RPE65 in visual chromophore production and regeneration is well established and has been extensively reviewed (e.g., [23]). The other two family members, BCMO1 and β,β-carotene-9,10-dioxygenase 2 (BCDO2), are true carotenoid-oxygenases and

BCMO1 is the key enzyme for vitamin A production

In mammals, the molecular and biochemical basis of vitamin A function has been well established. The vitamin A-derivative 11-cis-retinal serves as chromophore of cone and rod visual pigments [40]. Moreover, vitamin A is the precursor for all-trans-retinoic acid (RA), which is required for a wide range of biological processes, including embryonic and fetal development, cell differentiation and metabolic control. This hormone-like compound is the ligand of retinoic acid receptors (RARs) that

Regulation of intestinal vitamin A production

The small intestine is responsible for absorbing dietary lipids such as carotenoids and delivering them to the organism as triglyceride-rich lipoproteins. Intestinal lipid absorption is a complex process that evidently depends on membrane receptors/transporters [46]. For carotenoids, it is now clear that scavenger receptors such as SR-B1 and CD36 facilitate their absorption [47]. Additionally, SR-BI also facilitates the intestinal absorption of tocopherols (vitamin E) [48]. Studies in a

BCMO1 expression in peripheral tissues and the embryo

In humans, substantial amounts of absorbed β-carotene are not cleaved in the intestine by BCMO1 (up to 40% of dietary intake) [52] and along with other lipids become incorporated in chylomicrons and found associated with circulating lipoproteins [53]. Circulating carotenoids in association with lipoproteins can be then taken up by the lipoprotein specific receptors. In mice, BCMO1 is expressed in both the intestine and liver but also in peripheral tissues, including the mammalian embryo [10],

BCMO1 deficiency affects embryonic retinoid metabolism

Loredana Quadro and coworkers provided evidence that BCMO1 can maintain retinoid homeostasis in embryonic tissues of VAD mice [71]. In an elegant genetic approach, they generated RBP^−/− BCMO1^−/− double mutant female mice. In RBP-deficiency, mice depend on a continuous dietary vitamin A supply (RE in chylomicrons) [75]. These double mutant mice were crossed with RBP^−/− male mice so that dames were deficient both for RBP and BCMO1 whereas their offspring carried a functional BCMO1 allele.

A role of BCMO1 in the regulation of body fat reserves

Among the many functions attributed to retinoids, its putative role in adipocyte biology and the regulation of body fat reserves has generated clinical and scientific interest. The vitamin A derivative RA acid has been shown to influence adipocyte differentiation [77], [78] and fat deposition [79], mitochondrial uncoupling [80], [81], oxidative metabolism [82], [83] and adipokine expression [84], [85], [86], [87] in adipose tissues. These effects are mediated in part via the classical retinoic

BCDO2 and apocarotenoid signaling molecules

Though the role of BCMO1 for retinoid metabolism has been well established, less is known about the second carotenoid-oxygenase, BCDO2. As described above, biochemical studies indicate that this enzyme displays broad substrate specificity and converts both carotenes and xanthophylls by oxidative cleavage at the 9′,10′ and 9,10 double bonds. Apocarotenoids such as β-14′-apocarotenal and β-13′-apocarotenal have shown to influence the activities of nuclear receptors such RXR and PPARα and γ [104],

BCDO2, carotenoid homeostasis, and mitochondria

The broad substrate specificity of BCDO2 implicates this enzyme in the metabolism of both carotene and xanthophylls. A critical role of BCDO2 for xanthophyll metabolism was substantiated by findings in chickens. The yellow skin color of chickens (xanthophylls) is determined by cis-acting and tissue-specific regulatory mutation(s) that inhibit expression of BCDO2 in skin [111]. Additionally, it was shown that mutations in BCDO2 gene cause the yellow fat phenotype (xanthophyll accumulation) of

Concluding remarks

A ubiquitous family of non-heme iron oxygenases has been identified that modify double bonds of carotenoids and their apocarotenoid derivatives by trans-to-cis isomerization and oxidative cleavage. Mammalian genomes encode three distinct family members. RPE65 is the isomerase in the visual cycle, whereas BCMO1 and BCDO2 catalyze the oxidative cleavage of carotenoids. BCMO1 cleaves at the C15,C15′ double bond and has a limited substrate specificity for proretinoid carotenoids such as

Acknowledgments

The authors would like to thank Drs. Ouliana Ziouzenkova and Earl Harrison for the invitation to contribute this article to this special issue of BBA. This work was supported by the National Institute of Health grant EY019641. Darwin Babino was supported by a visual science training grant (NIH T32-EY07157).

References (120)

D.M. Snodderly
Evidence for protection against age-related macular degeneration by carotenoids and antioxidant vitamins
Am. J. Clin. Nutr.
(1995)
A.R. Moise et al.
Related enzymes solve evolutionarily recurrent problems in the metabolism of carotenoids
Trends Plant Sci.
(2005)
O.A. Sineshchekov et al.
Rhodopsin-mediated photosensing in green flagellated algae
Trends Plant Sci.
(1999)
C. Kiefer et al.
Identification and characterization of a mammalian enzyme catalyzing the asymmetric oxidative cleavage of provitamin A
J. Biol. Chem.
(2001)
J. von Lintig et al.
Filling the gap in vitamin A research. Molecular identification of an enzyme cleaving beta-carotene to retinal
J. Biol. Chem.
(2000)
A. Wyss et al.
Cloning and expression of beta, beta-carotene 15,15′-dioxygenase
Biochem. Biophys. Res. Commun.
(2000)
H. Schmidt et al.
The carotenase AtCCD1 from Arabidopsis thaliana is a dioxygenase
J. Biol. Chem.
(2006)
J. von Lintig et al.
The biochemical and structural basis for trans-to-cis isomerization of retinoids in the chemistry of vision
Trends Biochem. Sci.
(2010)
S. Hessel et al.
CMO1 deficiency abolishes vitamin A production from beta-carotene and alters lipid metabolism in mice
J. Biol. Chem.
(2007)
M. Jin et al.
Rpe65 is the retinoid isomerase in bovine retinal pigment epithelium
Cell
(2005)

G. Moiseyev et al.

RPE65 is an iron(II)-dependent isomerohydrolase in the retinoid visual cycle

J. Biol. Chem.

(2006)

A. Lindqvist et al.

Biochemical properties of purified recombinant human beta-carotene 15,15′-monooxygenase

J. Biol. Chem.

(2002)

K.Q. Hu et al.

The biochemical characterization of ferret carotene-9′,10′-monooxygenase catalyzing cleavage of carotenoids in vitro and in vivo

J. Biol. Chem.

(2006)

A. Lindqvist et al.

Loss-of-function mutation in carotenoid 15,15′-monooxygenase identified in a patient with hypercarotenemia and hypovitaminosis A

J. Nutr.

(2007)

I. Shmarakov et al.

Hepatic stellate cells are an important cellular site for beta-carotene conversion to retinoid

Arch. Biochem. Biophys.

(2010)

E. Reboul et al.

Scavenger receptor class B type I (SR-BI) is involved in vitamin E transport across the enterocyte

J. Biol. Chem.

(2006)

J. von Lintig et al.

Towards a better understanding of carotenoid metabolism in animals

Biochim. Biophys. Acta

(2005)

E.J. Johnson et al.

Distribution of orally administered beta-carotene among lipoproteins in healthy men

Am. J. Clin. Nutr.

(1992)

P. Borel et al.

Low and high responders to pharmacological doses of beta-carotene: proportion in the population, mechanisms involved and consequences on beta-carotene metabolism

J. Lipid Res.

(1998)

Y. Lin et al.

Variability of the conversion of beta-carotene to vitamin A in women measured by using a double-tracer study design

Am. J. Clin. Nutr.

(2000)

A.J. Edwards et al.

A novel extrinsic reference method for assessing the vitamin A value of plant foods

Am. J. Clin. Nutr.

(2001)

L. Ferrucci et al.

Common variation in the beta-carotene 15,15′-monooxygenase 1 gene affects circulating levels of carotenoids: a genome-wide association study

Am. J. Hum. Genet.

(2009)

H. Bachmann et al.

Feedback regulation of beta, beta-carotene 15,15′-monooxygenase by retinoic acid in rats and chickens

J. Nutr.

(2002)

Y. Seino et al.

Isx participates in the maintenance of vitamin A metabolism by regulation of beta-carotene 15,15′-monooxygenase (Bcmo1) expression

J. Biol. Chem.

(2008)

S.F. Cai et al.

Differentiation-dependent expression and localization of the class B type I scavenger receptor in intestine

J. Lipid Res.

(2001)

A. During et al.

Carotenoid uptake and secretion by CaCo-2 cells: beta-carotene isomer selectivity and carotenoid interactions

J. Lipid Res.

(2002)

J. Paik et al.

Expression and characterization of a murine enzyme able to cleave beta-carotene. The formation of retinoids

J. Biol. Chem.

(2001)

T.M. Redmond et al.

Identification, expression, and substrate specificity of a mammalian beta-carotene 15,15′-dioxygenase

J. Biol. Chem.

(2001)

W. Yan et al.

Cloning and characterization of a human beta, beta-carotene-15,15′-dioxygenase that is highly expressed in the retinal pigment epithelium

Genomics

(2001)

W. Kuri-Harcuch

Differentiation of 3T3 F442A cells into adipocytes is inhibited by retinoic acid

Differentiation

(1982)

R. Alvarez et al.

A novel regulatory pathway of brown fat thermogenesis. Retinoic acid is a transcriptional activator of the mitochondrial uncoupling protein gene

J. Biol. Chem.

(1995)

F. Felipe et al.

Effects of retinoic acid administration and dietary vitamin A supplementation on leptin expression in mice: lack of correlation with changes of adipose tissue mass and food intake

Biochim. Biophys. Acta

(2005)

N. Shaw et al.

Retinoic acid is a high affinity selective ligand for the peroxisome proliferator-activated receptor beta/delta

J. Biol. Chem.

(2003)

E.D. Rosen

The transcriptional basis of adipocyte development

Prostaglandins Leukot. Essent. Fatty Acids

(2005)

G.P. Lobo et al.

{beta},{beta}-Carotene decreases peroxisome proliferator receptor {gamma activity and reduces lipid storage capacity of adipocytes in a {beta},{beta}-carotene oxygenase 1-dependent manner

J. Biol. Chem.

(2010)

S.M. O'Byrne et al.

Retinoid absorption and storage is impaired in mice lacking lecithin: retinol acyltransferase (LRAT)

J. Biol. Chem.

(2005)

B. Demmig-Adams et al.

Antioxidants in photosynthesis and human nutrition

Science

(2002)

B. Faivre et al.

Immune activation rapidly mirrored in a secondary sexual trait

Science (New York, N.Y.)

(2003)

J.D. Blount et al.

Carotenoid modulation of immune function and sexual attractiveness in zebra finches

Science (New York, N.Y.)

(2003)

S. Beatty et al.

Macular pigment and risk for age-related macular degeneration in subjects from a Northern European population

Invest. Ophthalmol. Vis. Sci.

(2001)

N.I. Krinsky

The biological activity of carotenoid metabolites

K.H. Jung

The distinct signaling mechanisms of microbial sensory rhodopsins in Archaea, Eubacteria and Eukarya

Photochem. Photobiol.

(2007)

T. Moore

Vitamin A and carotene. VI. The conversion of carotene to vitamin A in vivo

Biochem. J.

(1930)

P. Karrer et al.

Über die Konstitution des Lycopins und Carotins

Helv. Chim. Acta

(1930)

J.A. Olson et al.

The enzymatic cleavage of beta-carotene into vitamin A by soluble enzymes of rat liver and intestine

Proc. Natl Acad. Sci. U. S. A.

(1965)

D.S. Goodman et al.

Biosynthesis of vitamin a with rat intestinal enzymes

Science (New York, N.Y.)

(1965)

S.H. Schwartz et al.

Specific oxidative cleavage of carotenoids by VP14 of maize

Science (New York, N.Y.)

(1997)

A. Prado-Cabrero et al.

Retinal biosynthesis in fungi: characterization of the carotenoid oxygenase CarX from Fusarium fujikuroi

Eukaryot. Cell

(2007)

S. Ruch et al.

Retinal biosynthesis in Eubacteria: in vitro characterization of a novel carotenoid oxygenase from Synechocystis sp. PCC 6803

Mol. Microbiol.

(2005)

M.G. Leuenberger et al.

The reaction mechanism of the enzyme-catalyzed central cleavage of beta-carotene to retinal

Angew. Chem. Int. Ed. Engl.

(2001)

Cited by (104)

Bioaccumulated provitamin A in black soldier fly larvae is bioavailable and capable of improving vitamin A status of gerbils
2023, Food Research International
The aim was to study whether provitamin A (proVA), which can bioaccumulate in black soldier fly larvae (BSFL), is bioavailable and can restore VA status in mammals. A model for studying the metabolism of this vitamin, the gerbil, was either fed a standard diet (C+ group), a diet without VA (C-), a diet in which VA was provided by β-carotene (β-C) from sweet potatoes (SP), or a diet in which VA was provided by β-C from BSFL that had been fed sweet potatoes (BSFL). The animals were killed at the end of the supplementation period and β-C, retinol and retinyl esters were measured in plasma and liver. As expected β-C was not detected in plasma and liver of the C+ and C- groups. β-C concentrations were lower (p < 0.05) in plasma and liver of the BSFL group as compared to the SP group. Liver retinol and retinyl ester concentrations were lower in the C- group than in all the other groups (p < 0.05). These concentrations were not significantly different in the C+ and SP groups while they were lower in the BSFL group (p < 0.05 for retinyl oleate and retinyl linoleate). In total, the liver stock of retinol equivalent was almost twice lower in the BSFL group than in the SP group. Thus, β-C present in the BSFL matrix is bioavailable and capable of improving VA status, but this matrix decreases its effectiveness by a factor of around two compared to the sweet potato matrix.
Functional analysis of ABCG2 gene in pigment transport of Neocaridina denticulata sinensis
2022, Gene
Citation Excerpt :
β -carotene oxygenase 2 (BCO2) is responsible for asymmetric cleavage of β -carotene to β -APO-10-carotene (C27) and β -ionone (C13). BCO2 decomposes the excess carotenoids to reduce the oxidative metabolic stress of carotenoids and protect the important organelles in vivo, and prevent the adverse reactions caused by excessive carotenoid content (Kiefer et al., 2001; Lobo et al., 2012a; Lobo et al. 2012b; Amengual et al., 2011). In mice, BCO2 controls carotenoid homeostasis and participates in the production of carotenoid signaling molecules (Amengual et al., 2011; Amengual et al., 2013; Costabile et al., 2016).
Many strains of Neocaridina denticulata sinensis (cherry shrimp) possess vivid body colors. However, the molecular underpinnings of these various body colors are scarcely understood. To study the role of the ABCG2 gene in the pigmentation of cherry shrimp, four strains (red, yellow, blue, and wild strains) were sampled. The sequence and expression pattern of ABCG2in tissues and embryos were analyzed, and the distribution of ABCG2 was also explored via WFISH (whole mount flurescence in situ hybridization). And further, RNA interference (RNAi) was used to explore the role of ABCG2 in body color deposition. The results showed that the ABCG2 sequence contained the conserved motif of Walker A, Walker B, Q-loop, d-loop, and H-loop. In tissues, ABCG2 was highly expressed in the epidermis of the four strains. During development stages, it was first expressed at the cleavage stage, then decreased at the gastrula stage, with the lowest expression at the pre-nauplius stage. From the metanauplius stage, its expression level was significantly upregulated until it reached the highest level at the membrane-zoea stage. WFISH showed that ABCG2 was first expressed at the cleavage stage in all four strains, and its distribution was similar from the cleavage stage to the before-zoea stage. The strongest positive signals were observed at the membrane-zoea stage, which was consistent with the qPCR results. Moreover, at the membrane-zoea stage, the positive signals of the four strains were mainly distributed in the compound eye and appendages. RNAi knockdown of ABCG2 encumbered the development of compound eye pigment cells (CEPCs) and erythrophores. It had effects on the expressions of other genes related to body color. These results suggest that ABCG2 is involved in the development of compound eye and the proliferation of erythrophores. This study provides new ideas for the cultivation of novel body colors in cherry shrimp at the molecular level.
Using black soldier fly larvae reared on fruits and vegetables waste as a sustainable dietary source of provitamin a carotenoids
2021, Food Chemistry
We showed that black soldier fly larvae reared on fruits and vegetables rich in provitamin A carotenoids can accumulate significant amounts of these vitamin A precursors. Using a simulated gastro-intestinal digestion model, we demonstrated that α- and β-carotene from the larvae are as bioaccessible as from the fruits and vegetables they were reared on. We calculated that provitamin A carotenoid-rich larvae have the capacity to provide more vitamin A than fruits and vegetables rich in these molecules. Remarkably, the incorporation of usual quantities of these larvae in feed could cover the needs of several production animals for this vitamin. Thus, our findings suggest that rearing black soldier fly larvae on by-products or waste rich in provitamin A carotenoids could be a sustainable strategy to recycle a fraction of vitamin A back into the food chain and could represent a new approach to fight against vitamin A deficiency.
Transcriptome and functional responses to absence of astaxanthin in Atlantic salmon fed low marine diets
2021, Comparative Biochemistry and Physiology - Part D: Genomics and Proteomics
High content of carotenoids in tissues of salmonid species suggests possible functional importance, which has so far remained unclear. The objective of this study was to investigate the effect of astaxanthin on performance and gene expression of sea water adapted Atlantic salmon (Salmo salar) fed diets with low content of marine ingredients (7.5% fishmeal and 5% fish oil). Salmon with start weight 197 g were fed two diets with identical proximate composition except for the content of astaxanthin (<1 and 48 mg/kg, respectively) for 84 days. Absence of dietary astaxanthin caused significant transcriptome changes revealed with DNA microarray. The growth rate was not optimal for the two diet groups but was not affected by dietary astaxanthin concentration. Accumulation of lipid in the intestine and liver was found in salmon fed both diets, indicating malabsorption of lipid. Salmon fed the diet without astaxanthin had larger livers and higher fat content in liver due to accumulation of triglycerides, but the difference in fat content was not significant. Transcriptome responses in different organs suggested that lack of dietary astaxanthin may have functional consequences in salmon fed low marine diets. In the intestine of astaxanthin deprived salmon, decreased expression was observed in a suite of immune genes including genes of innate antiviral immunity, transporters and enzymes of glycan metabolism. Transcriptome responses in liver suggested effect of absence of astaxanthin on lipid metabolism and especially on increased biosynthesis of terpenoids and steroids and only minor effects on immune genes. The greatest transcriptome changes were observed in skeletal muscle in the absence of astaxanthin, with an up-regulation of immune-related genes (119) and multiple genes with well-established association with stress. The condition resembled a mild inflammation of the muscle. Small or moderate scale of gene expression changes were in concordance with equal growth performance of fish fed both diets, however their character may indicate potential risk of absence of dietary carotenoids.
Volatile organic compounds (VOCs) allow sensitive differentiation of biological soil quality
2021, Soil Biology and Biochemistry
Understanding the change in function of the biological community under different soil conditions is key to effective soil quality monitoring and mitigation of soil degradation. Current measures of biological soil quality suffer from drawbacks with most techniques having high expense, low throughput or a narrow focus on one component of the community. The aim of this study was to assess the use of volatilomics as a method to profile the soil microbial community and compare the technique to phospholipid fatty acid (PLFA) profiling as a measure of biological soil quality. An agricultural grassland soil (Eutric Cambisol) was subjected to a range of stresses in replicate laboratory mesocosms. Treatments included the imposition of hypoxia/anoxia by flooding with freshwater or saltwater in the presence or absence of plant residues. The volatile organic compound (VOC) and PLFA profile of each treatment was then compared to unamended mesocosms. We hypothesized that the VOC fingerprint of soil would be highly responsive to changes in microbial metabolic status/functioning and thus provide a complementary approach to PLFAs for evaluating soil biological health. We also hypothesized that the VOC profile would have greater discriminatory power than PLFAs for determining differences between soil treatments. A headspace solid phase microextraction (HSSPME) method coupled with gas chromatography quadrupole-time of flight mass spectrometry (GC/Q-TOFMS) was used to analyse the broad spectrum of VOCs produced by each soil. Across all soil treatments 514 unique VOC peaks were detected. Overall, VOCs showed greater sensitivity than the PLFA analysis in separating soil quality treatments. Eighteen individual VOCs were identified which were primarily responsible for this separation (e.g. indole, α-ionone, isophorone, 3-octanone, p-cresol, 2-ethyl-phenol). Anaerobic soils amended with residues showed the greatest separation from other treatments, with most of this differentiation associated with ten individual VOCs. The anaerobic soils also showed a significant reduction in the number of VOCs emitted but an increase in total VOC emissions. In conclusion, our findings provide evidence that soil VOCs rapidly respond to changes in soil quality and therefore hold great potential as a novel functionally relevant diagnostic measure of biological soil quality.
Enzymology of vertebrate carotenoid oxygenases
2020, Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Mammals and higher vertebrates including humans have only three members of the carotenoid cleavage dioxygenase family of enzymes. This review focuses on the two that function as carotenoid oxygenases. β-Carotene 15,15′-dioxygenase (BCO1) catalyzes the oxidative cleavage of the central 15,15′ carbon-carbon double of β-carotene bond by addition of molecular oxygen. The product of the reaction is retinaldehyde (retinal or β-apo-15-carotenal). Thus, BCO1 is the enzyme responsible for the conversion of provitamin A carotenoids to vitamin A. It also cleaves the 15,15′ bond of β-apocarotenals to yield retinal and of lycopene to yield apo-15-lycopenal. β-Carotene 9′,10′-dioxygenase (BCO2) catalyzes the cleavage of the 9,10 and 9′,10′ double bonds of a wider variety of carotenoids, including both provitamin A and non-provitamin A carotenoids, as well as the xanthophylls, lutein and zeaxanthin. Indeed, the enzyme shows a marked preference for utilization of these xanthophylls and other substrates with hydroxylated terminal rings. Studies of the phenotypes of BCO1 null, BCO2 null, and BCO1/2 double knockout mice and of humans with polymorphisms in the enzymes, has clarified the role of these enzymes in whole body carotenoid and vitamin A homeostasis. These studies also demonstrate the relationship between enzyme expression and whole body lipid and energy metabolism and oxidative stress.
In addition, relationships between BCO1 and BCO2 and the development or risk of metabolic diseases, eye diseases and cancer have been observed. While the precise roles of the enzymes in the pathophysiology of most of these diseases is not presently clear, these gaps in knowledge provide fertile ground for rigorous future investigations.
This article is part of a Special Issue entitled Carotenoids: Recent Advances in Cell and Molecular Biology edited by Johannes von Lintig and Loredana Quadro.

View all citing articles on Scopus

^☆: This article is part of a Special Issue entitled Retinoid and Lipid Metabolism.

View full text

ReviewMammalian Carotenoid-oxygenases: Key players for carotenoid function and homeostasis☆

Abstract

Section snippets

Out of the wild green yonder: carotenoid cleaving enzymes

Mammalian genomes encode three different CCE family members

BCMO1 is the key enzyme for vitamin A production

Regulation of intestinal vitamin A production

BCMO1 expression in peripheral tissues and the embryo

BCMO1 deficiency affects embryonic retinoid metabolism

A role of BCMO1 in the regulation of body fat reserves

BCDO2 and apocarotenoid signaling molecules

BCDO2, carotenoid homeostasis, and mitochondria

Concluding remarks

Acknowledgments

Am. J. Clin. Nutr.

Trends Plant Sci.

Trends Plant Sci.

J. Biol. Chem.

J. Biol. Chem.

Biochem. Biophys. Res. Commun.

J. Biol. Chem.

Trends Biochem. Sci.

J. Biol. Chem.

Cell

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

J. Nutr.

Arch. Biochem. Biophys.

J. Biol. Chem.

Biochim. Biophys. Acta

Am. J. Clin. Nutr.

J. Lipid Res.

Am. J. Clin. Nutr.

Am. J. Clin. Nutr.

Am. J. Hum. Genet.

J. Nutr.

J. Biol. Chem.

J. Lipid Res.

J. Lipid Res.

J. Biol. Chem.

J. Biol. Chem.

Genomics

Differentiation

J. Biol. Chem.

Biochim. Biophys. Acta

J. Biol. Chem.

Prostaglandins Leukot. Essent. Fatty Acids

J. Biol. Chem.

J. Biol. Chem.

Antioxidants in photosynthesis and human nutrition

Science

Immune activation rapidly mirrored in a secondary sexual trait

Science (New York, N.Y.)

Carotenoid modulation of immune function and sexual attractiveness in zebra finches

Science (New York, N.Y.)

Macular pigment and risk for age-related macular degeneration in subjects from a Northern European population

Invest. Ophthalmol. Vis. Sci.

The biological activity of carotenoid metabolites

The distinct signaling mechanisms of microbial sensory rhodopsins in Archaea, Eubacteria and Eukarya

Photochem. Photobiol.

Vitamin A and carotene. VI. The conversion of carotene to vitamin A in vivo

Biochem. J.

Über die Konstitution des Lycopins und Carotins

Helv. Chim. Acta

The enzymatic cleavage of beta-carotene into vitamin A by soluble enzymes of rat liver and intestine

Proc. Natl Acad. Sci. U. S. A.

Biosynthesis of vitamin a with rat intestinal enzymes

Science (New York, N.Y.)

Specific oxidative cleavage of carotenoids by VP14 of maize

Science (New York, N.Y.)

Retinal biosynthesis in fungi: characterization of the carotenoid oxygenase CarX from Fusarium fujikuroi

Eukaryot. Cell

Retinal biosynthesis in Eubacteria: in vitro characterization of a novel carotenoid oxygenase from Synechocystis sp. PCC 6803

Mol. Microbiol.

The reaction mechanism of the enzyme-catalyzed central cleavage of beta-carotene to retinal

Angew. Chem. Int. Ed. Engl.

Review
Mammalian Carotenoid-oxygenases: Key players for carotenoid function and homeostasis☆