The molecular aspects of absorption and metabolism of carotenoids and retinoids in vertebrates.
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ABSTRACT:
SUBMITTER: Widjaja-Adhi MAK
PROVIDER: S-EPMC7244374 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Carotenoids are orange, yellow, and red lipophilic pigments present in many fruit and vegetables, as well as other food groups. Some carotenoids contribute to vitamin A requirements. The consumption and blood concentrations of specific carotenoids have been associated with reduced risks of a number of chronic conditions. However, the interpretation of large, population-based observational and prospective clinical trials is often complicated by the many extrinsic and intrinsic factors that affect the physiologic response to carotenoids. Extrinsic factors affecting carotenoid bioavailability include food-based factors, such as co-consumed lipid, food processing, and molecular structure, as well as environmental factors, such as interactions with prescription drugs, smoking, or alcohol consumption. Intrinsic, physiologic factors associated with blood and tissue carotenoid concentrations include age, body composition, hormonal fluctuations, and variation in genes associated with carotenoid absorption and metabolism. To most effectively investigate carotenoid bioactivity and to utilize blood or tissue carotenoid concentrations as biomarkers of intake, investigators should either experimentally or statistically control for confounding variables affecting the bioavailability, tissue distribution, and metabolism of carotene and xanthophyll species. Although much remains to be investigated, recent advances have highlighted that lipid co-consumption, baseline vitamin A status, smoking, body mass and body fat distribution, and genetics are relevant covariates for interpreting blood serum or plasma carotenoid responses. These and other intrinsic and extrinsic factors are discussed, highlighting remaining gaps in knowledge and opportunities for future research. To provide context, we review the state of knowledge with regard to the prominent health effects of carotenoids.
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Project description:Naturally occurring retinoids (retinol, retinal, retinoic acid, retinyl esters) are a subclass of β-apocarotenoids, defined by the length of the polyene side chain. Provitamin A carotenoids are metabolically converted to retinal (β-apo-15-carotenal) by the enzyme β-carotene-15,15'-dioxygenase (BCO1) that catalyzes the oxidative cleavage of the central C=C double bond. A second enzyme β-carotene-9'-10'-dioxygenase cleaves the 9',10' bond to yield β-apo-10'-carotenal and β-ionone. Chemical oxidation of the other double bonds leads to the generation of other β-apocarotenals. Like retinal, some of these β-apocarotenals are metabolically oxidized to the corresponding β-apocarotenoic acids or reduced to the β-apocarotenols, which in turn are esterified to β-apocarotenyl esters. Other metabolic fates such as 5,6-epoxidation also occur as for retinoids. Whether the same enzymes are involved remains to be understood. β-Apocarotenoids occur naturally in plant-derived foods and, therefore, are present in the diet of animals and humans. However, the levels of apocarotenoids are relatively low, compared with those of the parent carotenoids. Moreover, human studies show that there is little intestinal absorption of intact β-apocarotenoids. It is possible that they are generated in vivo under conditions of oxidative stress. The β-apocarotenoids are structural analogs of the naturally occurring retinoids. As such, they may modulate retinoid metabolism and signaling. In deed, those closest in size to the C-20 retinoids-namely, β-apo-14'-carotenoids (C-22) and β-apo-13-carotenone (C-18) bind with high affinity to purified retinoid receptors and function as retinoic acid antagonists in transactivation assays and in retinoic acid induction of target genes. The possible pathophysiologic relevance in human health remains to be determined.
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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.
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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.
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Project description:BackgroundVitamin A is essential for physiological processes like vision and immunity. Vitamin A's effect on gut microbiome composition, which affects absorption and metabolism of other vitamins, is still unknown. Here we examined the relationship between gut metagenome composition and six vitamin A-related metabolites (two retinoid: -retinol, 4 oxoretinoic acid (oxoRA) and four carotenoid metabolites, including beta-cryptoxanthin and three carotene diols).MethodsWe included 1053 individuals from the TwinsUK cohort with vitamin A-related metabolites measured in serum and faeces, diet history, and gut microbiome composition assessed by shotgun metagenome sequencing. Results were replicated in 327 women from the ZOE PREDICT-1 study.ResultsFive vitamin A-related serum metabolites were positively correlated with microbiome alpha diversity (r = 0.15 to r = 0.20, p < 4 × 10-6). Carotenoid compounds were positively correlated with the short-chain fatty-acid-producing bacteria Faecalibacterium prausnitzii and Coprococcus eutactus. Retinol was not associated with any microbial species. We found that gut microbiome composition could predict circulating levels of carotenoids and oxoretinoic acid with AUCs ranging from 0.66 to 0.74 using random forest models, but not retinol (AUC = 0.52). The healthy eating index (HEI) was strongly associated with gut microbiome diversity and with all carotenoid compounds, but not retinoids. We investigated the mediating role of carotenoid compounds on the effect of a healthy diet (HEI) on gut microbiome diversity, finding that carotenoids significantly mediated between 18 and 25% of the effect of HEI on gut microbiome alpha diversity.ConclusionsOur results show strong links between circulating carotene compounds and gut microbiome composition and potential links to a healthy diet pattern.
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