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malfunction
cardiac dysfunction in beta-carotene-15,15-dioxygenase-deficient mice is associated with altered retinoid and lipid metabolism. Bco1-/- mice show an increase in heart levels of retinol, nonesterified fatty acids, and ceramides and a decrease in heart triglycerides. These lipid changes are accompanied by elevations in levels of genes important to retinoid metabolism, specifically retinol dehydrogenase 10 and retinol-binding protein 4, as well as genes involved in lipid metabolism, including peroxisome proliferator-activated receptor-gamma, lipoprotein lipase, Cd36, stearoyl-CoA desaturase 1, and fatty acid synthase. The mutant mice show compromised heart function. But the total absence of Bco1 does not substantially affect beta-apo-carotenoid concentrations in the heart. Phenotype, overview
malfunction
deficiency of BCO1 in the liver does not significantly affect retinol or retinyl ester concentrations compared to the wild-type group, even though retinyl ester levels tend to be lower in the absence of BCO1. BCO1-/- and wild-type female mice reveal a statistically significant decrease in retinol content in the heart, pancreas, spleen, eye and adipose tissue of the knockout females. Retinol concentrations are greater in the lungs of the BCO1-/- females compared to wild-type
malfunction
mice lacking beta-carotene-15,15'-dioxygenase exhibit reduced serum testosterone, prostatic androgen receptor signaling, and prostatic cellular proliferation. Bco1 disruption also impacts diverse physiological end points independent of dietary carotenoid feeding, including expression of genes controlling androgen metabolism. co1 disruption significantly reduced Leydig cell number and decreased testicular mRNA expression of Hsd17b3, suggesting inhibition of testicular testosterone synthesis. Decreased androgen receptor nuclear localization in the dorsolateral prostate lobes of Bco1-/- mice. Analysis of prostatic morphology suggests a decreases in gland size and secretion, supported by reduced expression of the proliferation marker Ki-67 in Bco1-/- prostates. Genes differentially regulated in prostates of Bco1?/? mice, overview. Bco1 disruption alters prostatic morphology, reduces prostatic androgen receptor localization, and alters prostatic androgen signaling, but does not impact androgen receptor expression
physiological function
crucial enzyme in development and metabolism that governs the de novo entry of vitamin A from plant-derived precursors
physiological function
beta-carotene-15,15'-dioxygenase (BCO1) cleaves dietary carotenoids at the central 15,15' double bond, most notably acting on beta-carotene to yield retinal
physiological function
dietary carotenoids like beta-carotene are converted within the body either to retinoid, via beta-carotene-15,15'-dioxygenase (BCO1), or to beta-apo-carotenoids, via beta-carotene-9',10'-oxygenase 2. Some beta-apo-carotenoids are potent antagonists of retinoic acid receptor (RAR)-mediated transcriptional regulation, which is required to ensure normal heart development and functions. BCO1 modulates heart metabolism and function, possibly by altering levels of cofactors required for the actions of nuclear hormone receptors
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Redmond, T.M.; Gentleman, S.; Duncan, T.; Yu, S.; Wiggert, B.; Gantt, E.; Cunningham, F.X.
Identification, expression, and substrate specificity of a mammalian beta-carotene 15,15'-dioxygenase
J. Biol. Chem.
276
6560-6565
2001
Mus musculus (Q9JJS6), Mus musculus
brenda
Poliakov, E.; Gentleman, S.; Cunningham, F.X.; Miller-Ihli, N.J.; Redmond, T.M.
Key role of conserved histidines in recombinant mouse beta-carotene 15,15-monooxygenase-1 activity
J. Biol. Chem.
280
29217-29223
2005
Mus musculus (Q9JJS6), Mus musculus
brenda
Fierce, Y.; de Morais Vieira, M.; Piantedosi, R.; Wyss, A.; Blaner, W.S.; Paik, J.
In vitro and in vivo characterization of retinoid synthesis from beta-carotene
Arch. Biochem. Biophys.
472
126-138
2008
Homo sapiens, Mus musculus
brenda
Seino, Y.; Miki, T.; Kiyonari, H.; Abe, T.; Fujimoto, W.; Kimura, K.; Takeuchi, A.; Takahashi, Y.; Oiso, Y.; Iwanaga, T.; Seino, S.
Isx participates in the maintenance of vitamin A metabolism by regulation of beta-carotene 15,15'-monooxygenase (Bcmo1) expression
J. Biol. Chem.
283
4905-4911
2008
Mus musculus (Q9JJS6)
brenda
Oberhauser, V.; Voolstra, O.; Bangert, A.; von Lintig, J.; Vogt, K.
NinaB combines carotenoid oxygenase and retinoid isomerase activity in a single polypeptide
Proc. Natl. Acad. Sci. USA
105
19000-19005
2008
Drosophila melanogaster (Q9VFS2), Galleria mellonella, Mus musculus
brenda
Kim, Y.-S.; Kim, N.-H.; Kim, H.-J.; Lee, J.-K.; Kim, S.-W.; Oh, D.-K.
Effective production of retinal from beta-carotene using recombinant mouse beta-carotene 15,15'-monooxygenase
Appl. Microbiol. Biotechnol.
76
1339-1345
2007
Mus musculus (Q9JJS6), Mus musculus
brenda
Lietz, G.; Lange, J.; Rimbach, G.
Molecular and dietary regulation of beta,beta-carotene 15,15-monooxygenase 1 (BCMO1)
Arch. Biochem. Biophys.
502
8-16
2010
Cavia porcellus, Gallus gallus, Oryctolagus cuniculus, Homo sapiens, Mus musculus, Rattus norvegicus, Sus scrofa
brenda
Pham, D.N.; Leclerc, D.; Levesque, N.; Deng, L.; Rozen, R.
beta,beta-carotene 15,15'-monooxygenase and its substrate beta-carotene modulate migration and invasion in colorectal carcinoma cells
Am. J. Clin. Nutr.
98
413-422
2013
Homo sapiens (Q9HAY6), Mus musculus (Q9JJS6), Mus musculus
brenda
Kowatz, T.; Babino, D.; Kiser, P.; Palczewski, K.; von Lintig, J.
Characterization of human beta,beta-carotene-15,15'-monooxygenase (BCMO1) as a soluble monomeric enzyme
Arch. Biochem. Biophys.
539
214-222
2013
Homo sapiens (Q9HAY6), Homo sapiens, Mus musculus (Q9JJS6), Mus musculus, Mus musculus C57/BL6 / 129 Sv (Q9JJS6)
brenda
Amengual, J.; Widjaja-Adhi, M.A.; Rodriguez-Santiago, S.; Hessel, S.; Golczak, M.; Palczewski, K.; von Lintig, J.
Two carotenoid-oxygenases contribute to mammalian pro-vitamin A metabolism
J. Biol. Chem.
288
34081-34096
2013
Mus musculus (Q9JJS6)
brenda
Lietz, G.; Oxley, A.; Boesch-Saadatmandi, C.; Kobayashi, D.
Importance of beta,beta-carotene 15,15-monooxygenase 1 (BCMO1) and beta,beta-carotene 9,10-dioxygenase 2 (BCDO2) in nutrition and health
Mol. Nutr. Food Res.
56
241-250
2012
Cavia porcellus (H0VRY9), Danio rerio, Drosophila melanogaster, Gallus gallus (Q9I993), Homo sapiens (Q9HAY6), Homo sapiens, Mus musculus (Q9JJS6), Mustela putorius furo, no activity in Arabidopsis thaliana, no activity in Zea mays, Oryctolagus cuniculus (G1SEP0), Rattus norvegicus (Q91XT5)
brenda
Amengual, J.; Gouranton, E.; van Helden, Y.G.; Hessel, S.; Ribot, J.; Kramer, E.; Kiec-Wilk, B.; Razny, U.; Lietz, G.; Wyss, A.; Dembinska-Kiec, A.; Palou, A.; Keijer, J.; Landrier, J.F.; Bonet, M.L.; von Lintig, J.
Beta-carotene reduces body adiposity of mice via BCMO1
PLoS ONE
6
e20644
2011
Mus musculus (Q9JJS6)
brenda
Lee, S.A.; Jiang, H.; Trent, C.M.; Yuen, J.J.; Narayanasamy, S.; Curley, R.W.; Harrison, E.H.; Goldberg, I.J.; Maurer, M.S.; Blaner, W.S.
Cardiac dysfunction in beta-carotene-15,15-dioxygenase-deficient mice is associated with altered retinoid and lipid metabolism
Am. J. Physiol. Heart Circ. Physiol.
307
H1675-H1684
2014
Mus musculus (Q9JJS6)
brenda
Smith, J.W.; Ford, N.A.; Thomas-Ahner, J.M.; Moran, N.E.; Bolton, E.C.; Wallig, M.A.; Clinton, S.K.; Erdman, J.W.
Mice lacking beta-carotene-15,15'-dioxygenase exhibit reduced serum testosterone, prostatic androgen receptor signaling, and prostatic cellular proliferation
Am. J. Physiol. Regul. Integr. Comp. Physiol.
311
R1135-R1148
2016
Mus musculus (Q9JJS6), Mus musculus C57BL/6J (Q9JJS6)
brenda
Kim, Y.K.; Zuccaro, M.V.; Costabile, B.K.; Rodas, R.; Quadro, L.
Tissue- and sex-specific effects of beta-carotene 15,15' oxygenase (BCO1) on retinoid and lipid metabolism in adult and developing mice
Arch. Biochem. Biophys.
572
11-18
2015
Mus musculus (Q9JJS6), Mus musculus C57BL/6 (Q9JJS6)
brenda