Importance of β,β‐carotene 15,15′‐monooxygenase 1 (BCMO1) and β,β‐carotene 9′,10′‐dioxygenase 2 (BCDO2) in nutrition and health

Oxley, Anthony; Boesch-Saadatmandi, Christine; Kobayashi, Daisuke

doi:10.1002/mnfr.201100387

Cited by 76 publications

(65 citation statements)

References 89 publications

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“…These findings reveal that retinoic acid negatively regulates BCMO expression via the signaling of RARs and ISX, indicating that regulation occurs in response to diet with a negative feedback mechanism (21,28). BCMO is not only the key enzyme in retinal and retinoic acid production from b-carotene, but it is also active as a regulatory factor of lipid metabolism (29). The promoter region of human and mice BCMO genes contains a peroxisome proliferator response element, and BCMO expression is transcriptionally regulated by PPARg, which is a member of the nuclear superfamily and has a critical role in controlling energy, lipid, and glucose metabolism (30,31).…”

Section: Discussionmentioning

confidence: 83%

Retinol Status and Expression of Retinol-Related Proteins in Methionine-Choline Deficient Rats

Miyazaki

Takitani

Koh

et al. 2014

J Nutr Sci Vitaminol

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Vitamin A (retinol) plays an important role in vision and has pleiotropic functions in immune response, hematopoiesis, fertility, cell differentiation, growth, and morphogenesis (1). Both retinol deficiency and excessive doses of retinol cause malformations in the embryos of many vertebrate species, demonstrating that retinol plays an important role in embryogenesis. Retinoic acids, derivatives of retinol, act as the ligands of retinoic acid receptors (RAR) and retinoid X receptors (RXR), which are members of the nuclear receptor superfamily and are ligand-dependent transcriptional factors (2). RAR and RXR have subtypes (a, b, and g), and 9-cis retinoic acid (an isomer of retinoic acid) binds RARs and RXRs, whereas all-trans retinoic acid binds only RARs. Both types of retinoic acid receptors transcriptionally regulate the expression of target genes and exert multiple physiological functions.Dietary retinol has 2 major forms: retinyl esters derived from animal sources and provitamin A carotenoids, mainly in the form of b-carotene, derived from plants (3,4). Dietary retinyl esters are emulsified with fatty acids and bile salts and then micellized before hydrolysis in the lumen of the small intestine for retinol uptake. In the enterocytes, retinol is rapidly re-esterified with long-chain fatty acids. b-Carotene is absorbed in intestinal mucosal cells and then cleaved for retinal formation. b-Carotene 15,15′-monooxygenase (BCMO), the key enzyme of this process, cleaves b-carotene into 2 molecules of retinal, which are then esterified to retinyl ester in the intestine (4). Retinyl esters that are incorporated into chylomicrons are secreted from enterocytes and transferred to the liver through the lymphatic circulation. Chylomicrons containing retinyl esters are taken up by the liver and transferred to hepatic stellate cells (HSCs) for storage. Retinol in the liver is esterified by the enzyme lecithin:retinol acyltransferase (LRAT) to form retinyl esters. The transfer of retinol in the liver is mediated by cellular retinol binding protein (CRBP)-I, which delivers retinol to retinol binding protein (RBP) for secretion into the circulation. Retinoic acid levels are tightly regulated at the biosynthesis and oxidation stages (3). Retinol is reversibly oxidized to retinal by retinol dehydrogenases, and retinal is irreversibly oxidized to retinoic acid by members of the retinal dehydrogenase (ALDH) family. As mentioned above, the biological actions of retinoic acid isomers (all-trans and 9-cis forms) are conducted through their role as RAR and RXR ligands. Retinoic acids are oxidized by the cytochrome P450 26 family (CYP26A1, CYP26B1, and CYP26C1), following which their metabolites are conjugated with glucuronic acid.Non-alcoholic fatty liver disease (NAFLD) is one of the most common diseases in developed countries, and Pediatrics, Osaka Rosai Hospital, 1179-3 Nagasone-cho, Kita-ku, Sakai, Osaka 591-8025, Japan (Received October 9, 2013 Summary Retinol and its derivative, retinoic acid, have pleiotropic functions includ...

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Section: Discussionmentioning

confidence: 83%

Retinol Status and Expression of Retinol-Related Proteins in Methionine-Choline Deficient Rats

Miyazaki

Takitani

Koh

et al. 2014

J Nutr Sci Vitaminol

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“…Beta-ionone (EAFUS/cosmetics) is also formed in animals by beta-carotene oxygenase 2 (BCO2) which converts betacarotene to β-10'-apocarotenal and β-ionone, en route to the synthesis of Vitamin A [254]. It does not activate retinoid receptors RARA or RARB [255] but binds to a retinol binding protein, beta-lactoglobulin B, involved in the oral delivery of retinol to neonates [256].…”

Section: Other Endogenous Compounds Targeting Autism Genesmentioning

confidence: 99%

Autism genes are selectively targeted by environmental pollutants including pesticides, heavy metals, bisphenol A, phthalates and many others in food, cosmetics or household products

Carter

Blizard

2016

Neurochemistry International

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“…BCO2 (β, β-carotene-9',10'-oxygenase2) is an enzyme that catalyzes the asymmetric cleavage of carotenoids in the inner membrane of mitochondria [15]. Recent controversial research findings demonstrated that BCO2 may not be activated in the human macula where carotenoids preferentially accumulate [16,17], suggesting that BCO2 may not only function as a carotenoid cleavage enzyme which warrants further investigation.…”

Section: Introductionmentioning

confidence: 99%

Hypothalamic mitochondria in energy homeostasis and obesity

Guo¹,

Wu²,

Wang³

et al. 2016

Integr Mol Med

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Obesity, which is largely due to energy imbalance, has emerged as one of the most serious health issues in the world. The hypothalamus is the most important organ to regulate feeding behavior and energy expenditure through nutrient sensing and signal integration from central and peripheral pathways. As the main organelle to produce energy, mitochondria play a critical role in energy homeostasis from the organelle level. Besides providing a platform for the oxidation of fuel substrates, mitochondria are also involved in a variety of cell signaling pathways and modulate energy homeostasis through mitochondrial dynamics. Mitochondrial dysfunction may lead to obesity due to inadequate ATP production, oxidative stress, endoplasmic reticulum stress, and inflammation. β, β-carotene-9',10'-oxygenase2 (BCO2) is a mitochondrial enzyme that catalyzes the asymmetric cleavage of both provitamin A and non-provitamin A carotenoids. This enzyme is localized to the inner mitochondrial membrane, where the electron transport chain is located. Besides the enzymatic function, BCO2 is important for mitochondrial function and is genetically associated with interleukin-18. Moreover, BCO2 protein expression is suppressed in obese and diabetic mice. Given that the important role of BCO2 in mitochondrial structure and function, and the key position of the hypothalamus in energy balance, BCO2 may play a new role in maintaining metabolic homeostasis that has been overlooked before. The mutation of BCO2 might lead to the impairment of whole body energy homeostasis through hypothalamic mitochondrial dysfunction. Here we will be presenting the updates on hypothalamic mitochondria in cellular energy homeostasis and discussing the potential of BCO2 in regulation of hypothalamic mitochondria in health and obesity.

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Importance of β,β‐carotene 15,15′‐monooxygenase 1 (BCMO1) and β,β‐carotene 9′,10′‐dioxygenase 2 (BCDO2) in nutrition and health

Cited by 76 publications

References 89 publications

Retinol Status and Expression of Retinol-Related Proteins in Methionine-Choline Deficient Rats

Retinol Status and Expression of Retinol-Related Proteins in Methionine-Choline Deficient Rats

Autism genes are selectively targeted by environmental pollutants including pesticides, heavy metals, bisphenol A, phthalates and many others in food, cosmetics or household products

Hypothalamic mitochondria in energy homeostasis and obesity

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