The molecular aspects of absorption and metabolism of carotenoids and retinoids in vertebrates

Vitamin A is an essential nutrient necessary for numerous basic physiological functions, including reproduction and development, immune cell differentiation and communication, as well as the perception of light. To evade the dire consequences of vitamin A deficiency, vertebrates have evolved specialized metabolic pathways that enable the absorption, transport, and storage of vitamin A acquired from dietary sources as preformed retinoids or provitamin A carotenoids. This evolutionary advantage requires a complex interplay between numerous specialized retinoid-transport proteins, receptors, and enzymes. Recent advances in molecular and structural biology resulted in a rapid expansion of our understanding of these processes at the molecular level. This progress opened new avenues for the therapeutic manipulation of retinoid homeostasis. In this review, we summarize current research related to the biochemistry of carotenoid and retinoid-processing proteins with special emphasis on the structural aspects of their physiological actions. This article is part of a Special Issue entitled Carotenoids recent advances in cell and molecular biology edited by Johannes von Lintig and Loredana Quadro.     

SigF controls carotenoid pigment production and affects transformation efficiency and hydrogen peroxide sensitivity in Mycobacterium smegmatis

Carotenoids are complex lipids that are known for acting against photodynamic injury and free radicals. We demonstrate here that sigma(F) is required for carotenoid pigment production in Mycobacterium smegmatis. We further show that a sigF mutant exhibits a transformation efficiency 10(4)-fold higher than that of the parental strain, suggesting that sigma(F) regulates the production of components affecting cell wall permeability. In addition, a sigF mutant showed an increased sensitivity to hydrogen peroxide. An in silico search of the M. smegmatis genome identified a number of SigF consensus sites, including sites upstream of the carotenoid synthesis locus, which explains its SigF regulation.     

Carotenoids and fatty liver disease: Current knowledge and research gaps

Carotenoids form an important part of the human diet, consumption of which has been associated with many health benefits. With the growing global burden of liver disease, increasing attention has been paid on the possible beneficial role that carotenoids may play in the liver. This review focuses on carotenoid actions in non-alcoholic fatty liver disease (NAFLD), and alcoholic liver disease (ALD). Indeed, many human studies have suggested an association between decreased circulating levels of carotenoids and increased incidence of NAFLD and ALD. The literature describing supplementation of individual carotenoids in rodent models of NAFLD and ALD is reviewed, with particular attention paid to β-carotene and lycopene, but also including β-cryptoxanthin, lutein, zeaxanthin, and astaxanthin. The effect of beta-carotene oxygenase 1 and 2 knock-out mice on hepatic lipid metabolism is also discussed. In general, there is evidence to suggest that carotenoids have beneficial effects in animal models of both NAFLD and ALD. Mechanistically, these benefits may occur via three possible modes of action: 1) improved hepatic antioxidative status broadly attributed to carotenoids in general, 2) the generation of vitamin A from β-carotene and β-cryptoxanthin, leading to improved hepatic retinoid signaling, and 3) the generation of apocarotenoid metabolites from β-carotene and lycopene, that may regulate hepatic signaling pathways. Gaps in our knowledge regarding carotenoid mechanisms of action in the liver are highlighted throughout, and the review ends by emphasizing the importance of dose effects, mode of delivery, and mechanism of action as important areas for further study. This article is part of a Special Issue entitled Carotenoids recent advances in cell and molecular biology edited by Johannes von Lintig and Loredana Quadro.     

苹果类胡萝卜素研究进展

类胡萝卜素是苹果果实色泽形成的一个重要影响因子,其种类和含量决定果实是否具有良好的外观和丰富的营养。本文综述了近年来有关苹果果实类胡萝卜素方面的研究进展,并对苹果类胡萝卜素的种类和含量,苹果发育和贮藏过程中类胡萝卜素含量的变化规律,生物合成途径中相关基因的表达,以及环境因子对类胡萝卜素积累的影响等方面进行了阐述。     

Carotenoids and carotenoid conversion products in adipose tissue biology and obesity: Pre-clinical and human studies

Antiobesity activities of carotenoids and carotenoid conversion products (CCPs) have been demonstrated in pre-clinical studies, and mechanisms behind have begun to be unveiled, thus suggesting these compounds may help obesity prevention and management. The antiobesity action of carotenoids and CCPs can be traced to effects in multiple tissues, notably the adipose tissues. Key aspects of the biology of adipose tissues appear to be affected by carotenoid and CCPs, including adipogenesis, metabolic capacities for energy storage, release and inefficient oxidation, secretory function, and modulation of oxidative stress and inflammatory pathways. Here, we review the connections of carotenoids and CCPs with adipose tissue biology and obesity as revealed by cell and animal intervention studies, studies addressing the role of endogenous retinoid metabolism, and human epidemiological and intervention studies. We also consider human genetic variability influencing carotenoid and vitamin A metabolism, particularly in adipose tissues, as a potentially relevant aspect towards personalization of dietary recommendations to prevent or manage obesity and optimize metabolic health. This article is part of a Special Issue entitled Carotenoids recent advances in cell and molecular biology edited by Johannes von Lintig and Loredana Quadro.     

Carotenoids: New Applications of “Old” Pigments

Carotenoids represent a large group of mainly red, orange, and yellow natural metabolites mainly involved in regulation of many metabolic processes. Carotenoids are beneficial for human health. Current study describes the importance, chemical composition and functioning of carotenoids. It is well known that carotenoids support pigments acting in light absorbance mechanisms during photosynthesis, and are known to protect the chlorophyll molecules from oxidative stress and reactive oxygen species (ROS) damage. Carotenoids are involved in signaling processes in plants, responses to environmental stresses, pollination, germination and reproduction, and development regulation. As nutrients of strong antioxidant activity that is primarily linked to their polyene molecular structure, the carotenoids are reported as immune-enhancement and anticancer agents, which are also involved in prevention of eye-, gastric and neurocognitive disorders, and in regulation of obesity and anti-ageing. Concerning the wide prospective applications of carotenoids as pharmaceuticals and nutraceuticals, there are some critical aspects associated with carotenoids’ bioavailability and challenges in their bioengineering. This mostly refers to the needs for identification and cloning of genes responsible for carotenoid biosynthesis and transformation and related development of transgenic carotenoid-rich crops. In the recent years, technologies of micro- and nanoencapsulation have addressed the needs of carotenoid entrapping to enhance their bioavailability, solubility and chemical stability, and to ensure the target delivery and manifestation of their strong antioxidant and other biological activity. Among standard and some advanced analytic tools for carotenoid determination (e.g., High performance liquid chromatography-HPLC, Liquid chromatography–mass spectrometry-LC-MS, Ultra high performance liquid chromatography-UHPLC, High-performance thin-layer chromatography-HPTLC and others), the vibrational spectroscopy techniques, primarily Raman spectroscopy coupled with chemometric modeling, opened a new era in carotenoid research and application.     

Carotenoid biofortification in crop plants: citius,altius, fortius

Carotenoids are indispensable for human health, required as precursors of vitamin A and efficient antioxidants. However, these plant pigments that play a vital role in photosynthesis are represented at insufficient levels in edible parts of several crops, which creates a need for increasing their content or optimizing their composition through biofortification. In particular, vitamin A deficiency, a severe health problem affecting the lives of millions in developing countries, has triggered the development of a series of high-provitamin A crops, including Golden Rice as the best-known example. Further carotenoid-biofortified crops have been generated by using genetic engineering approaches or through classical breeding. In this review, we depict carotenoid metabolism in plants and provide an update on the development of carotenoid-biofortified plants and their potential to meet needs and expectations. Furthermore, we discuss the possibility of using natural variation for carotenoid biofortification and the potential of gene editing tools. This article is part of a Special Issue entitled Carotenoids recent advances in cell and molecular biology edited by Johannes von Lintig and Loredana Quadro.     

Carotenoid accumulation and function in seeds and non-green tissues

Carotenoids are plant pigments that function as antioxidants, hormone precursors, colourants and essential components of the photosynthetic apparatus. Carotenoids accumulate in nearly all types of plastids, not just the chloroplast, and are thus found in most plant organs and tissues, albeit at trace levels in some tissues. In this review we summarise the current knowledge of the carotenoid content of non-green plastids and discuss what is known about the regulation of their biosynthesis in roots, fruits, flowers, tubers and seeds. The emphasis is on food crops as carotenoids are essential components of human diets, primarily as some are precursors of vitamin A. The low carotenoid content of many staple foods, such as cereals, can exacerbate dietary deficiencies. The World Health Organisation has estimated that more than 100 million children are vitamin A-deficient and up to 500,000 of these children become blind each year. Many of these children die within 12 months of going blind. Thus, understanding the regulation of carotenoid accumulation in food crops, especially tubers and cereals, should facilitate improvements to nutritional value with potentially significant health benefits.     

Biological functions of carotenoids--diversity and evolution

Carotenoids first emerged in archaebacteria as lipids reinforcing cell membranes. To serve this function their long molecules have extremely rigid backbone due to the linear chain of usually 10 to 11 conjugated C=C bonds in transconfiguration--the length corresponding the thickness of hydrophobic zone of membrane which they penetrate as "molecular rivets". Carotenoids retain their membrane-reinforcing function in some fungi and animals. The general structure of carotenoid molecule, originally having evolved for mechanical functions in membranes, possess a number of other properties that were later used for independent functions. The most striking fact is that these properties proved to fit some new functions to perfection. The polyene chain of 9-11 double bonds absorbs light precisely in the gap of chlorophyll absorption--function as accessory light-harvesting pigments in all plants; Unique arrangement of electronic levels owing to the by polyene chain structure makes carotenoids the only natural compounds capable of excitation energy transfer both (i) from carotenoid excited state to chlorophyll in the light-harvesting complex and (ii) from triplet chlorophyll or singlet oxygen to carotenoid in photosynthetic reaction centers--protection of RC from photodamage. The linear system of conjugated C=C bonds provides high reducing potential of carotenoid molecules making them potent antioxidants in lipid formations. Still, there is a lack of evidence of the chemical antioxidant function of carotenoids, especially in higher organisms; most data demonstrate an antioxidant ability rather than a function. Carotenoids have many other independent biological functions, including: specific coloration patterns in plants and animals, screening from excessive light and spectral filtering, defense of egg proteins from proteases in some invertebrates; the direct carotenoid derivative--retinal--acts as visual pigment in all animals and as chromophore in bacteriorhodopsin photosynthesis, retinoic acid in animals and abscisic acid in plants serve as hormones. All these functions utilize various properties (mechanical, electronic, stereospecific) of a single structure evolved in bacteria for a single membrane-reinforcing function, thus demonstrating an example of pure evolutionary preadaptation. One of the practical conclusions that can be reached by reviewing uniquely diverse properties and functions of carotenoids is that, when considering possible mechanisms of their effects in organisms (e.g., anticarcinogenic action), all their functional traits should be taken into account.     

The use of carotenoids and oxonol VI as probes for membrane potential in proteoliposomes

Carotenoids present in lipids extracted from the cyanobacterium Synechococcus 6716 indicate trans-membrane potential in proteoliposomes reconstituted from these lipids and the ATPase complex isolated from the same organism. A carotenoid absorbance band shift to a longer wavelength is obtained with valinomycin-induced potassium ion diffusion potentials, irrespective of the polarity of the potassium gradient. In contrast to this, the (externally added) probe oxonol VI only shows an absorbance band shift when the external potassium ion concentration is higher than the internal one. In liposomes without ATPase complex, no carotenoid absorbance band shifts were observed.     

Study of 'Redhaven' peach and its white-fleshed mutant suggests a key role of CCD4 carotenoid dioxygenase in carotenoid and norisoprenoid volatile metabolism

Background  

Carotenoids are plant metabolites which are not only essential in photosynthesis but also important quality factors in determining the pigmentation and aroma of flowers and fruits. To investigate the regulation of carotenoid metabolism, as related to norisoprenoids and other volatile compounds in peach (Prunus persica L. Batsch.), and the role of carotenoid dioxygenases in determining differences in flesh color phenotype and volatile composition, the expression patterns of relevant carotenoid genes and metabolites were studied during fruit development along with volatile compound content. Two contrasted cultivars, the yellow-fleshed 'Redhaven' (RH) and its white-fleshed mutant 'Redhaven Bianca' (RHB) were examined.     

The role of the retinoid receptor,RAR/RXR heterodimer,in liver physiology

Activated by retinoids, metabolites of vitamin A, the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs) play important roles in a wide variety of biological processes, including embryo development, homeostasis, cell proliferation, differentiation and death. In this review, we summarized the functional roles of nuclear receptor RAR/RXR heterodimers in liver physiology. Specifically, RAR/RXR modulate the synthesis and metabolism of lipids and bile acids in hepatocytes, regulate cholesterol transport in macrophages, and repress fibrogenesis in hepatic stellate cells. We have also listed the specific genes that carry these functions and how RAR/RXR regulate their expression in liver cells, providing a mechanistic view of their roles in liver physiology. Meanwhile, we pointed out many questions regarding the detailed signaling of RAR/RXR in regulating the expression of liver genes, and hope future studies will address these issues.     

Structural basis of carotenoid cleavage: From bacteria to mammals

Carotenoids and their metabolic derivatives serve critical functions in both prokaryotic and eukaryotic cells, including pigmentation, photoprotection and photosynthesis as well as cell signaling. These organic compounds are also important for visual function in vertebrate and non-vertebrate organisms. Enzymatic transformations of carotenoids to various apocarotenoid products are catalyzed by a family of evolutionarily conserved, non-heme iron-containing enzymes named carotenoid cleavage oxygenases (CCOs). Studies have revealed that CCOs are critically involved in carotenoid homeostasis and essential for the health of organisms including humans. These enzymes typically display a high degree of regio- and stereo-selectivity, acting on specific positions of the polyene backbone located in their substrates. By oxidatively cleaving and/or isomerizing specific double bonds, CCOs generate a variety of apocarotenoid isomer products. Recent structural studies have helped illuminate the mechanisms by which CCOs mobilize their lipophilic substrates from biological membranes to perform their characteristic double bond cleavage and/or isomerization reactions. In this review, we aim to integrate structural and biochemical information about CCOs to provide insights into their catalytic mechanisms.     

茶类胡萝卜素研究进展

类胡萝卜素是茶(Camellia sinensis (L.) O. Ktze.)中一类重要的光合色素,具有光保护、抗氧化等众多生理功能,同时也是脱落酸、独脚金内酯和胡萝卜内脂等植物激素的合成前体,在茶生长发育过程中起极其重要的作用。类胡萝卜素还是构成茶叶外形、叶底色泽的重要成分,也是茶叶重要致香物质的前体物,其种类、含量对茶叶品质起着至关重要的作用。本文对茶中类胡萝卜素种类、代谢途径及其对制茶品质的影响等方面的研究进展进行了综述,同时对茶类胡萝卜素下一步的研究方向进行了展望。     

Triacylglycerol lipases of the yeast

All eukaryotes including the yeast contain a lipid storage compartment which is named lipid particle, lipid droplet or oil body. Lipids accumulating in this subcellular fraction serve as a depot of energy and building blocks for membrane lipid synthesis. In the yeast, the major storage lipids are triacylglycerols (TGs) and steryl esters (SEs). An important step in the life cycle of these non-polar lipids is their mobilization from their site of storage and channeling of their degradation components to the appropriate metabolic pathways. A key step in this mobilization process is hydrolysis of TG and SE which is accomplished by lipases and hydrolases. In this review, we describe our recent knowledge of TG lipases from the yeast based on biochemical, molecular biological and cell biological information. We report about recent findings addressing the versatile role of TG lipases in lipid metabolism, and discuss non-polar lipid homeostasis and its newly discovered links to various cell biological processes in the yeast.     

Mechanistic understanding of β-cryptoxanthin and lycopene in cancer prevention in animal models

To better understand the potential function of carotenoids in the chemoprevention of cancers, mechanistic understanding of carotenoid action on genetic and epigenetic signaling pathways is critically needed for human studies. The use of appropriate animal models is the most justifiable approach to resolve mechanistic issues regarding protective effects of carotenoids at specific organs and tissue sites. While the initial impetus for studying the benefits of carotenoids in cancer prevention was their antioxidant capacity and pro-vitamin A activity, significant advances have been made in the understanding of the action of carotenoids with regards to other mechanisms. This review will focus on two common carotenoids, provitamin A carotenoid β-cryptoxanthin and non-provitamin A carotenoid lycopene, as promising chemopreventive agents or chemotherapeutic compounds against cancer development and progression. We reviewed animal studies demonstrating that β-cryptoxanthin and lycopene effectively prevent the development or progression of various cancers and the potential mechanisms involved. We highlight recent research that the biological functions of β-cryptoxanthin and lycopene are mediated, partially via their oxidative metabolites, through their effects on key molecular targeting events, such as NF-κB signaling pathway, RAR/PPARs signaling, SIRT1 signaling pathway, and p53 tumor suppressor pathways. The molecular targets by β-cryptoxanthin and lycopene, offer new opportunities to further our understanding of common and distinct mechanisms that involve carotenoids in cancer prevention.This article is part of a Special Issue entitled Carotenoids recent advances in cell and molecular biology edited by Johannes von Lintig and Loredana Quadro.     

Carotenoid and retinoid--two pigments in a gecko eye lens

The eye lenses of the Moroccan day gecko Quedenfeldtia trachyblepharus contain two different pigments: a retinoid (minor pigment) and a carotenoid (major pigment). The retinoid, all-trans 3, 4-didehydroretinol, is bound to iota-crystallin, which comprises only 2% of the total amount of crystallins. The carotenoid is associated to gammas-crystallin - comprising about 10% of total amount of crystallins--and causes the dark yellow colour of the lens. The absorption spectrum of the isolated carotenoid shows a major, triple-peaked band at 372, 392, and 416 nm and two minor peaks at 284 and 294 nm. This spectrum reminds of that of galloxanthin, a carotenoid found in oil droplets of some avian retinae. The absorption spectrum of the carotenoid-gammas-crystallin complex is shifted 6-8 nm bathochromically. In the lens, this complex absorbs ultraviolet and shortwave blue radiation, supposedly improving the optical quality of the dioptric apparatus and protecting the retina against photodamage. Both the retinoid and the carotenoid are present in eye cups. The lenticular carotenoid of Quedenfeldtia is the first example of a carotenoid in the lens of a terrestrial vertebrate with a sufficiently high concentration to be physiologically effective as a UV-filter. Additionally, it is unique in being the first example of a carotenoid associated with gammas-crystallin.     

Carotenoid biotechnology in plants for nutritionally improved foods

Carotenoids participate in light harvesting and are essential for photoprotection in photosynthetic plant tissues. They also furnish non-photosynthetic flowers and fruits with yellow to red colors to attract animals for pollination and dispersal of seeds. Although animals can not synthesize carotenoids de novo , carotenoid-derived products such as retinoids (including vitamin A) are required as visual pigments and signaling molecules. Dietary carotenoids also provide health benefits based on their antioxidant properties. The main pathway for carotenoid biosynthesis in plants and microorganisms has been virtually elucidated in recent years, and some of the identified biosynthetic genes have been successfully used in metabolic engineering approaches to overproduce carotenoids of interest in plants. Alternative approaches that enhance the metabolic flux to carotenoids by upregulating the production of their isoprenoid precursors or interfere with light-mediated regulation of carotenogenesis have been recently shown to result in increased carotenoid levels. Despite spectacular achievements in the metabolic engineering of plant carotenogenesis, much work is still ahead to better understand the regulation of carotenoid biosynthesis and accumulation in plant cells. New genetic and genomic approaches are now in progress to identify regulatory factors that might significantly contribute to improve the nutritional value of plant-derived foods by increasing their carotenoid levels.