Abstract
Pathways for xanthophyll metabolism have been proposed on the basis of several oxidation products of dietary xanthophylls detected in the tissues of fish, birds, and human subjects. No enzyme reaction had been characterized as responsible for the pathways until a mouse liver homogenate was found to oxidize the 3-hydroxy β-end of xanthophylls to a 3-oxo ε-end in the presence of a cofactor, NAD+. This oxidation consists of dehydrogenation to an unstable intermediate having a 3-oxo β-end group and the subsequent migration of a double bond. β,ε-Caroten-3′-one, a metabolite of β-cryptoxanthin, was found in human plasma, indicating that the same oxidative activity as that found in the mouse liver works in human tissues.
The oxidative cleavage of carotenoids is mediated by two dioxygenases: a central cleavage enzyme and an asymmetric cleavage enzyme. In mice, the latter enzyme was suggested to eliminate carotenoids in tissues, while in humans, this enzyme is inactivated, resulting in carotenoid accumulation. In this chapter, carotenoid metabolism in mammals is described in terms of the oxidation of functional groups and cleavage of the carbon skeleton.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Albert GI, Hoeller U, Schierle J, Neuringer M, Johnson EJ, Schalch W (2008) Metabolism of lutein and zeaxanthin in rhesus monkeys: identification of (3R,6′R)- and (3R,6′S)-3′-dehydro-lutein as common metabolites and comparison to humans. Comp Biochem Physiol B-Biochem Mol Biol 151(1):70–78
Amengual J, Lobo GP, Golczak M, Li HNM, Klimova T, Hoppel CL, Wyss A, Palczewski K, von Lintig J (2011) A mitochondrial enzyme degrades carotenoids and protects against oxidative stress. FASEB J 25(3):948–959. https://doi.org/10.1096/fj.10-173906
Asai A, Sugawara T, Ono H, Nagao A (2004) Biotransformation of fucoxanthinol into amarouciaxanthin A in mice and HepG2 cells: formation and cytotoxicity of fucoxanthin metabolites. Drug Metab Dispos 32(2):205–211
Asai A, Yonekura L, Nagao A (2008) Low bioavailability of dietary epoxyxanthophylls in humans. Br J Nutr 100:273–277
Berry SD, Davis SR, Beattie EM, Thomas NL, Burrett AK, Ward HE, Stanfield AM, Biswas M, Ankersmit-Udy AE, Oxley PE, Barnett JL, Pearson JF, van der Does Y, MacGibbon AHF, Spelman RJ, Lehnert K, Snell RG (2009) Mutation in bovine beta-carotene oxygenase 2 affects milk color. Genetics 182(3):923–926
Chew BP, Park JS (2004) Carotenoid action on the immune response. J Nutr 134(1):257S–261S
dela Sena C, Riedl KM, Narayanasamy S, Curley RW, Schwartz SJ, Harrison EH (2014) The human enzyme that converts dietary provitamin A carotenoids to vitamin A is a dioxygenase. J Biol Chem 289(19):13661–13666
Etoh H, Utsunomiya Y, Komori A, Murakami Y, Oshima S, Inakuma T (2000) Carotenoids in human blood plasma after ingesting paprika juice. Biosci Biotechnol Biochem 64(5):1096–1098
Gerhauser C, Klimo K, Hummer W, Holzer J, Petermann A, Garreta-Rufas A, Bohmer FD, Schreier P (2009) Identification of 3-hydroxy-beta-damascone and related carotenoid-derived aroma compounds as novel potent inducers of Nrf2-mediated phase 2 response with concomitant anti-inflammatory activity. Mol Nutr Food Res 53(10):1237–1244
Goodwin TW (1984) Mammals, vol II Animals. The Biochemistry of the carotenoids. Chapman and Hall, London
Hartmann D, Thurmann PA, Spitzer V, Schalch W, Manner B, Cohn W (2004) Plasma kinetics of zeaxanthin and 3′-dehydro-lutein after multiple oral doses of synthetic zeaxanthin. Am J Clin Nutr 79(3):410–417
Holger S, Kurtzer R, Eisenreich W, Schwab W (2006) The carotenase AtCCD1 from Arabidopsis thaliana is a dioxygenase. J Biol Chem 281(15):9845–9851
Hudon J (1994) Biotechnological applications of research on animal pigmentation. Biotechnol Adv 12(1):49–69
Khachik F, Beecher GR, Goli MB, Lusby WR, Smith JC Jr (1992) Separation and identification of carotenoids and their oxidation products in the extracts of human plasma. Anal Chem 64(18):2111–2122
Kiefer C, Hessel S, Lampert JM, Vogt K, Lederer MO, Breithaupt DE, von Lintig J (2001) Identification and characterization of a mammalian enzyme catalyzing the asymmetric oxidative cleavage of provitamin A. J Biol Chem 276(17):14110–14116
Kotake-Nara E, Asai A, Nagao A (2005) Neoxanthin and fucoxanthin induce apoptosis in PC-3 human prostate cancer cells. Cancer Lett 220(1):75–84
Leuenberger MG, Engeloch-Jarret C, Woggon W-D (2001) The reaction mechanism of the enzyme-catalyzed central cleavage of β -carotene to retinal. Angew Chem Int Ed 40(14):2613–2617
Li BX, Vachali PP, Gorusupudi A, Shen ZQ, Sharifzadeh H, Besch BM, Nelson K, Horvath MM, Frederick JM, Baehr W, Bernstein PS (2014) Inactivity of human beta,beta-carotene-9 ′, 10 ′-dioxygenase (BCO2) underlies retinal accumulation of the human macular carotenoid pigment. Proc Natl Acad Sci U S A 111(28):10173–10178
Lian FZ, Wang XD (2008) Enzymatic metabolites of lycopene induce Nrf2-mediated expression of phase II detoxifying/antioxidant enzymes in human bronchial epithelial cells. Int J Cancer 123(6):1262–1268
Lian FZ, Smith DE, Ernst H, Russell RM, Wang XD (2007) Apo-10′-lycopenoic acid inhibits lung cancer cell growth in vitro, and suppresses lung tumorigenesis in the A/J mouse model in vivo. Carcinogenesis 28(7):1567–1574
Lindqvist A, Sharvill J, Sharvill DE, Andersson S (2007) Loss-of-function mutation in carotenoid 15,15′-monooxygenase identified in a patient with hypercarotenemia and hypovitaminosis A(1-3). J Nutr 137(11):2346–2350
Lobo GP, Isken A, Hoff S, Babino D, von Lintig J (2012) BCDO2 acts as a carotenoid scavenger and gatekeeper for the mitochondrial apoptotic pathway. Development 139(16):2966–2977
LoPachin RM, Barber DS, Gavin T (2008) Molecular mechanisms of the conjugated alpha, beta-unsaturated carbonyl derivatives: relevance to neurotoxicity and neurodegenerative diseases. Toxicol Sci 104(2):235–249. https://doi.org/10.1093/toxsci/kfm301
Maeda H, Hosokawa M, Sashima T, Funayama K, Miyashita K (2005) Fucoxanthin from edible seaweed, Undaria pinnatifida, shows antiobesity effect through UCP1 expression in white adipose tissues. Biochem Biophys Res Commun 332(2):392–397
Matsuno T (2001) Aquatic animal carotenoids. Fish Sci 67(5):771–783
Matsuno T, Hirono T, Ikuno Y, Maoka T, Shimizu M, Komori T (1986) Isolation of three new carotenoids and proposed metabolic pathways of carotenoids in hen’s egg yolk. Comp Biochem Physiol B 84(4):477–481
McGraw KJ, Hill GE, Stradi R, Parker RS (2001) The influence of carotenoid acquisition and utilization on the maintenance of species-typical plumage pigmentation in male American goldfinches (Carduelis tristis) and Northern cardinals (Cardinalis cardinalis). Physiol Biochem Zool 74(6):843–852
Mein JR, Dolnikowski GG, Ernst H, Russell RM, Wang XD (2011) Enzymatic formation of apo-carotenoids from the xanthophyll carotenoids lutein, zeaxanthin and beta-cryptoxanthin by ferret carotene-9 ′,10 ′-monooxygenase. Arch Biochem Biophys 506(1):109–121
Murakami A, Takahashi D, Kinoshita T, Koshimizu K, Kim H, Yoshihiro A, Nakamura Y, Jiwajinda S, Terao J, Ohigashi H (2002) Zerumbone, a Southeast Asian ginger sesquiterpene, markedly suppresses free radical generation, pro-inflammatory protein production, and cancer cell proliferation accompanied by apoptosis: the alpha, beta-unsaturated carbonyl group is a prerequisite. Carcinogenesis 23(5):795–802
Nagao A, Maoka T, Ono H, Kotake-Nara E, Kobayashi M, Tomita M (2015) A 3-hydroxy beta-end group in xanthophylls is preferentially oxidized to a 3-oxo epsilon-end group in mammals. J Lipid Res 56(2):449–462
Nishino H, Murakoshi M, Ii T, Takemura M, Kuchide M, Kanazawa M, Mou XY, Wada S, Masuda M, Ohsaka Y, Yogosawa S, Satomi Y, Jinno K (2002) Carotenoids in cancer chemoprevention. Cancer Metastasis Rev 21(3–4):257–264
Park JS, Chew BP, Wong TS (1998) Dietary lutein absorption from marigold extract is rapid in BALB/c mice. J Nutr 128(10):1802–1806
Richard B, Conrad Hans E (1979) Search for the presence in egg yolk, in flowers of Caltha palustris and in autumn leaves of 3′-epilutein (=(3R,3′S,6′R)-β,ε-carotene-3,3′-diol) and 3′,O-didehydrolutein (=(3R,6′R)-3-hydroxy-β,ε-carotene-3′-one). Helv Chim Acta 62(8):2817–2824
Sugawara T, Baskaran V, Tsuzuki W, Nagao A (2002) Brown algae fucoxanthin is hydrolyzed to fucoxanthinol during absorption by Caco-2 human intestinal cells and mice. J Nutr 132(5):946–951
Sui X, Golczak M, Zhang J, Kleinberg KA, von Lintig J, Palczewski K, Kiser PD (2015) Utilization of dioxygen by carotenoid cleavage oxygenases. J Biol Chem 290(51):30212–30223. https://doi.org/10.1074/jbc.M115.696799
Thurmann PA, Schalch W, Aebischer JC, Tenter U, Cohn W (2005) Plasma kinetics of lutein, zeaxanthin, and 3 ′-dehydro-lutein after multiple oral doses of a lutein supplement. Am J Clin Nutr 82(1):88–97
Wang TTY, Edwards AJ, Clevidence BA (2013) Strong and weak plasma response to dietary carotenoids identified by cluster analysis and linked to beta-carotene 15,15′-monooxygenase 1 single nucleotide polymorphisms. J Nutr Biochem 24(8):1538–1546
Yonekura L, Kobayashi M, Terasaki M, Nagao A (2010) Keto-carotenoids are the major metabolites of dietary lutein and fucoxanthin in mouse tissues. J Nutr 140(10):1824–1831
Zeng S, Furr HC, Olson JA (1992) Metabolism of carotenoid analogs in humans. Am J Clin Nutr 56(2):433–439
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2021 Springer Nature Singapore Pte Ltd.
About this chapter
Cite this chapter
Nagao, A. (2021). Metabolism of Carotenoids in Mammals. In: Misawa, N. (eds) Carotenoids: Biosynthetic and Biofunctional Approaches. Advances in Experimental Medicine and Biology, vol 1261. Springer, Singapore. https://doi.org/10.1007/978-981-15-7360-6_6
Download citation
DOI: https://doi.org/10.1007/978-981-15-7360-6_6
Published:
Publisher Name: Springer, Singapore
Print ISBN: 978-981-15-7359-0
Online ISBN: 978-981-15-7360-6
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)