Studies on the relative biopotencies and intestinal absorption of different apo-beta-carotenoids in rats and chickens.
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ABSTRACT:
SUBMITTER: Sharma RV
PROVIDER: S-EPMC1163980 | biostudies-other | 1976 Aug
REPOSITORIES: biostudies-other
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Project description:Vitamin A deficiency is still a public health concern affecting millions of pregnant women and children. Retinoic acid, the active form of vitamin A, is critical for proper mammalian embryonic development. Embryos can generate retinoic acid from maternal circulating β-carotene upon oxidation of retinaldehyde produced via the symmetric cleavage enzyme β-carotene 15,15'-oxygenase (BCO1). Another cleavage enzyme, β-carotene 9',10'-oxygenase (BCO2), asymmetrically cleaves β-carotene in adult tissues to prevent its mitochondrial toxicity, generating β-apo-10'-carotenal, which can be converted to retinoids (vitamin A and its metabolites) by BCO1. However, the role of BCO2 during mammalian embryogenesis is unknown. We found that mice lacking BCO2 on a vitamin A deficiency-susceptible genetic background (Rbp4-/-) generated severely malformed vitamin A-deficient embryos. Maternal β-carotene supplementation impaired fertility and did not restore normal embryonic development in the Bco2-/-Rbp4-/- mice, despite the expression of BCO1. These data demonstrate that BCO2 prevents β-carotene toxicity during embryogenesis under severe vitamin A deficiency. In contrast, β-apo-10'-carotenal dose-dependently restored normal embryonic development in Bco2-/-Rbp4-/- but not Bco1-/-Bco2-/-Rbp4-/- mice, suggesting that β-apo-10'-carotenal facilitates embryogenesis as a substrate for BCO1-catalyzed retinoid formation. These findings provide a proof of principle for the important role of BCO2 in embryonic development and invite consideration of β-apo-10'-carotenal as a nutritional supplement to sustain normal embryonic development in vitamin A-deprived pregnant women.
| S-EPMC5995931 | biostudies-literature
Project description:Xanthophyll carotenoids, such as lutein, zeaxanthin and β-cryptoxanthin, may provide potential health benefits against chronic and degenerative diseases. Investigating pathways of xanthophyll metabolism are important to understanding their biological functions. Carotene-15,15'-monooxygenase (CMO1) has been shown to be involved in vitamin A formation, while recent studies suggest that carotene-9',10'-monooxygenase (CMO2) may have a broader substrate specificity than previously recognized. In this in vitro study, we investigated baculovirus-generated recombinant ferret CMO2 cleavage activity towards the carotenoid substrates zeaxanthin, lutein and β-cryptoxanthin. Utilizing HPLC, LC-MS and GC-MS, we identified both volatile and non-volatile apo-carotenoid products including 3-OH-β-ionone, 3-OH-α-ionone, β-ionone, 3-OH-α-apo-10'-carotenal, 3-OH-β-apo-10'-carotenal, and β-apo-10'-carotenal, indicating cleavage at both the 9,10 and 9',10' carbon-carbon double bond. Enzyme kinetic analysis indicated the xanthophylls zeaxanthin and lutein are preferentially cleaved over β-cryptoxanthin, indicating a key role of CMO2 in non-provitamin A carotenoid metabolism. Furthermore, incubation of 3-OH-β-apo-10'-carotenal with CMO2 lysate resulted in the formation of 3-OH-β-ionone. In the presence of NAD(+), in vitro incubation of 3-OH-β-apo-10'-carotenal with ferret hepatic homogenates formed 3-OH-β-apo-10'-carotenoic acid. Since apo-carotenoids serve as important signaling molecules in a variety of biological processes, enzymatic cleavage of xanthophylls by mammalian CMO2 represents a new avenue of research regarding vertebrate carotenoid metabolism and biological function.
| S-EPMC3026080 | biostudies-literature
Project description:Oleocanthal (OLC), a phenolic compound of extra virgin olive oil (EVOO), has emerged as a potential therapeutic agent against a variety of diseases due to its anti-inflammatory activity. The aim of the present study is to explore its in vivo intestinal absorption and metabolism. An in situ perfusion technique in rats was used, involving simultaneous sampling from the luminal perfusate and mesenteric blood. Samples were analysed by UHPLC-MS-MS for the presence of oleocanthal (OLC) and its metabolites. OLC was mostly metabolized by phase I metabolism, undergoing hydration, hydrogenation and hydroxylation. Phase II reactions (glucuronidation of hydrogenated OLC and hydrated metabolites) were observed in plasma samples. OLC was poorly absorbed in the intestine, as indicated by the low effective permeability coefficient (2.23 ± 3.16 × 10-5 cm/s) and apparent permeability coefficient (4.12 ± 2.33 × 10-6 cm/s) obtained relative to the values of the highly permeable reference compound levofloxacin (LEV). The extent of OLC absorption reflected by the area under the mesenteric blood-time curve normalized by the inlet concentration (AUC) was also lower than that of LEV (0.25 ± 0.04 vs. 0.64 ± 0.03, respectively). These results, together with the observed intestinal metabolism, suggest that OLC has a moderate-to-low oral absorption; but higher levels of OLC are expected to reach human plasma vs. rat plasma.
| S-EPMC7076358 | biostudies-literature
Project description:The sensory rhodopsin from Anabaena (Nostoc) sp. PCC7120 is the first cyanobacterial retinylidene protein identified. Here, we report on NosACO (Nostoc apo-carotenoid oxygenase), encoded by the ORF (open reading frame) all4284, as the candidate responsible for the formation of the required chromophore, retinal. In contrast with the enzymes from animals, NosACO converts beta-apo-carotenals instead of beta-carotene into retinal in vitro. The identity of the enzymatic products was proven by HPLC and gas chromatography-MS. NosACO exhibits a wide substrate specificity with respect to chain lengths and functional end-groups, converting beta-apo-carotenals, (3R)-3-hydroxy-beta-apo-carotenals and the corresponding alcohols into retinal and (3R)-3-hydroxyretinal respectively. However, kinetic analyses revealed very divergent Km and Vmax values. On the basis of the crystal structure of SynACO (Synechocystis sp. PCC6803 apo-carotenoid oxygenase), a related enzyme showing similar enzymatic activity, we designed a homology model of the native NosACO. The deduced structure explains the absence of beta-carotene-cleavage activity and indicates that NosACO is a monotopic membrane protein. Accordingly, NosACO could be readily reconstituted into liposomes. To localize SynACO in vivo, a Synechocystis knock-out strain was generated expressing SynACO as the sole carotenoid oxygenase. Western-blot analyses showed that the main portion of SynACO occurred in a membrane-bound form.
| S-EPMC1559462 | biostudies-literature
Project description:An increased intake of fruits and vegetables has been shown to be associated with reduced risk of cancer. In epidemiological studies, supplements of beta-carotene, which is abundant in fruits and vegetables, were not found to be beneficial in reducing the incidence of lung cancer in high-risk groups. Epoxycarotenoids are abundant in nature. 5,6-Epoxy-beta-carotene was much more active than beta-carotene in the induction of differentiation of NB4 cells [Duitsman, Becker, Barua and Olson (1996) FASEB J. 10, A732]. Epoxycarotenes may, therefore, have protective effects against cancer. In order to do this, however, epoxycarotenoids must be absorbed by the human body. There is no evidence that epoxycarotenoids, despite their abundance in dietary fruits and vegetables, are absorbed by humans. In this paper, it is demonstrated that orally administered dietary or synthetic epoxy-beta-carotenes are absorbed by humans, as indicated by their appearance in the circulating blood.
| S-EPMC1220165 | biostudies-other
Project description:1. The mechanism of absorption of phosphatidylcholine was studied in rats by injecting into the intestine phosphatidylcholine specifically labelled either in the fatty acid or in the glycerol moiety or with (32)P, when considerable amounts of 1-acyl-lysophosphatidylcholine were found in the intestinal lumen. 2-([(14)C]Acyl)phosphatidylcholine gave markedly more radioactive unesterified fatty acids in the lumen, compared with the 1-([(14)C]acyl) derivative. Some of the radioactivity from either the fatty acid or the glycerol moiety of the injected phosphatidylcholine appeared in the mucosal triacylglycerols. 2. Injection of (32)P-labelled phosphatidylcholine or (32)P-labelled lysophosphatidylcholine led to the appearance of radioactive glycerylphosphorylcholine, glycerophosphate and P(i) in the mucosa. 3. Rat mucosa was found to contain a highly active glycerylphosphorylcholine diesterase. 4. It was concluded that the dietary phosphatidylcholine is hydrolysed in the intestinal lumen by the pancreatic phospholipase A to 1-acylglycerylphosphorylcholine, which on entering the mucosal cell is partly reacylated to phosphatidylcholine, and the rest is further hydrolysed to glycerylphosphorylcholine, glycerophosphate, glycerol and P(i). The fatty acids and glycerophosphate are then reassembled to give triacylglycerols via the Kennedy (1961) pathway.
| S-EPMC1168028 | biostudies-other
Project description:Puerariae Lobatae Radix, known as Gegen in Chinese, is widely used to treat cardiovascular diseases, diabetes, and many other chronic illnesses. Flavonoids are the main active components in Gegen and are found in high concentrations in soybeans. Few studies, however, have focused on the effects of flavonoid-rich food on the absorption of Gegen. Here, we report an in vivo pharmacokinetic study on rats to explore the effects of soybean milk on the absorption of Gegen and an in vitro Ussing chamber study of puerarin intestinal transmembrane absorption. Area under the plasma concentration-time curve (AUC0-t ) and maximum plasma concentration (Cmax) values of puerarin in rats were significantly decreased after drinking soybean milk, when taking Gegen decoction or a Gegen patent medicine (P < 0.01). In the Ussing chamber experiment, cumulative transmission (Qtn) after 2?h and apparent permeability coefficient (Papp) were lower in the puerarin-daidzin and puerarin-soybean milk solution groups than in the puerarin group. Daidzin in soybean milk inhibited the transmembrane transport of puerarin, resulting in decreased bioavailability of puerarin in Gegen. The results of this study strongly suggest that Gegen should not be taken with flavonoid-rich food, particularly soybean products.
| S-EPMC5602493 | biostudies-literature
Project description:β-Carotene is an important source of vitamin A for the mammalian embryo, which depends on its adequate supply to achieve proper organogenesis. In mammalian tissues, β-carotene 15,15'-oxygenase (BCO1) converts β-carotene to retinaldehyde, which is then oxidized to retinoic acid, the biologically active form of vitamin A that acts as a transcription factor ligand to regulate gene expression. β-Carotene can also be cleaved by β-carotene 9',10'-oxygenase (BCO2) to form β-apo-10'-carotenal, a precursor of retinoic acid and a transcriptional regulator per se The mammalian embryo obtains β-carotene from the maternal circulation. However, the molecular mechanisms that enable its transfer across the maternal-fetal barrier are not understood. Given that β-carotene is transported in the adult bloodstream by lipoproteins and that the placenta acquires, assembles, and secretes lipoproteins, we hypothesized that the aforementioned process requires placental lipoprotein biosynthesis. Here we show that β-carotene availability regulates transcription and activity of placental microsomal triglyceride transfer protein as well as expression of placental apolipoprotein B, two key players in lipoprotein biosynthesis. We also show that β-apo-10'-carotenal mediates the transcriptional regulation of microsomal triglyceride transfer protein via hepatic nuclear factor 4α and chicken ovalbumin upstream promoter transcription factor I/II. Our data provide the first in vivo evidence of the transcriptional regulatory activity of β-apocarotenoids and identify microsomal triglyceride transfer protein and its transcription factors as the targets of their action. This study demonstrates that β-carotene induces a feed-forward mechanism in the placenta to enhance the assimilation of β-carotene for proper embryogenesis.
| S-EPMC5000097 | biostudies-other
Project description:The structures of a number of stereoisomers of carotenoids have been revealed in three-dimensional X-ray crystallographic investigations of pigment-protein complexes from photosynthetic organisms. Despite these structural elucidations, the reason for the presence of stereoisomers in these systems is not well understood. An important unresolved issue is whether the natural selection of geometric isomers of carotenoids in photosynthetic pigment-protein complexes is determined by the structure of the protein binding site or by the need for the organism to accomplish a specific physiological task. The association of cis isomers of a carotenoid with reaction centers and trans isomers of the same carotenoid with light-harvesting pigment-protein complexes has led to the hypothesis that the stereoisomers play distinctly different physiological roles. A systematic investigation of the photophysics and photochemistry of purified, stable geometric isomers of carotenoids is needed to understand if a relationship between stereochemistry and biological function exists. In this work we present a comparative study of the spectroscopy and excited state dynamics of cis and trans isomers of three different open-chain carotenoids in solution. The molecules are neurosporene (n=9), spheroidene (n=10), and spirilloxanthin (n=13), where n is the number of conjugated pi-electron double bonds. The spectroscopic experiments were carried out on geometric isomers of the carotenoids purified by high performance liquid chromatography (HPLC) and then frozen to 77 K to inhibit isomerization. The spectral data taken at 77 K provide a high resolution view of the spectroscopic differences between geometric isomers. The kinetic data reveal that the lifetime of the lowest excited singlet state of a cis-isomer is consistently shorter than that of its corresponding all-trans counterpart despite the fact that the excited state energy of the cis molecule is typically higher than that of the trans molecule. Quantum theoretical calculations on an n=9 linear polyene were carried out to examine this process. The calculations indicate that the electronic coupling terms are significantly higher for the cis isomer, and when combined with the Franck-Condon factors, predict internal conversion rates roughly double those of the all-trans species. The electronic effects more than offset the decrease in coupling efficiencies associated with the higher system origin energies and explain the observed shorter cis isomer lifetimes.
| S-EPMC2733370 | biostudies-literature
Project description:The structures of a number of stereoisomers of carotenoids have been revealed in three-dimensional X-ray crystallographic investigations of pigment-protein complexes from photosynthetic organisms. Despite these structural elucidations, the reason for the presence of stereoisomers in these systems is not well understood. An important unresolved issue is whether the natural selection of geometric isomers of carotenoids in photosynthetic pigment-protein complexes is determined by the structure of the protein binding site or by the need for the organism to accomplish a specific physiological task. The association of cis isomers of a carotenoid with reaction centers and trans isomers of the same carotenoid with light-harvesting pigment-protein complexes has led to the hypothesis that the stereoisomers play distinctly different physiological roles. A systematic investigation of the photophysics and photochemistry of purified, stable geometric isomers of carotenoids is needed to understand if a relationship between stereochemistry and biological function exists. In this work we present a comparative study of the spectroscopy and excited state dynamics of cis and trans isomers of three different open-chain carotenoids in solution. The molecules are neurosporene (n = 9), spheroidene (n = 10), and spirilloxanthin (n = 13), where n is the number of conjugated pi-electron double bonds. The spectroscopic experiments were carried out on geometric isomers of the carotenoids purified by high performance liquid chromatography (HPLC) and then frozen to 77 K to inhibit isomerization. The spectral data taken at 77 K provide a high resolution view of the spectroscopic differences between geometric isomers. The kinetic data reveal that the lifetime of the lowest excited singlet state of a cis-isomer is consistently shorter than that of its corresponding all-trans counterpart despite the fact that the excited state energy of the cis molecule is typically higher than that of the trans molecule. Quantum theoretical calculations on an n = 9 linear polyene were carried out to examine this process. The calculations indicate that the electronic coupling terms are significantly higher for the cis isomer, and when combined with the Franck-Condon factors, predict internal conversion rates roughly double those of the all-trans species. The electronic effects more than offset the decrease in coupling efficiencies associated with the higher system origin energies and explain the observed shorter cis isomer lifetimes.
| S-EPMC2823300 | biostudies-literature