Requirements for carotenoids in fish diets

Carotenoids are among the most widespread and important pigment classes in living organisms, and in marine animals, astaxanthin is the most commonly occurring red carotenoid. Carotenoids are vitamin A precursors and are fundamental in photosynthesis and light protection in plants. Increasing attention has been drawn to a possible light protection, cancer prevention and immune enhancement by carotenoids in mammals. Reported functions in fish range from a general enhancement of performance to specific functions in reproduction and metabolism. In this paper, we show that astaxanthin is essential for growth and survival of fish and crawfish, and discuss this fact in relation to the use of purified and semipurified diets in nutritional studies. The similarity in action of astaxanthin and canthaxanthin compared to α-tocopherol (vitamin E) and retinol (vitamin A) suggests that these two carotenoids should be listed among the fat soluble vitamins.     

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.     

Animal models in carotenoids research and lung cancer prevention

Numerous epidemiological studies have consistently demonstrated that individuals who eat more fruits and vegetables (which are rich in carotenoids) and who have higher serum β-carotene levels have a lower risk of cancer, especially lung cancer. However, two human intervention trials conducted in Finland and in the United States have reported contrasting results with high doses of β-carotene supplementation increasing the risk of lung cancer among smokers. The failure of these trials to demonstrate actual efficacy has resulted in the initiation of animal studies to reproduce the findings of these two studies and to elucidate the mechanisms responsible for the harmful or protective effects of carotenoids in lung carcinogenesis. Although these studies have been limited by a lack of animal models that appropriately represent human lung cancer induced by cigarette smoke, ferrets and A/J mice are currently the most widely used models for these types of studies. There are several proposed mechanisms for the protective effects of carotenoids on cigarette smoke-induced lung carcinogenesis, and these include antioxidant/prooxidant effects, modulation of retinoic acid signaling pathway and metabolism, induction of cytochrome P450, and molecular signaling involved in cell proliferation and/or apoptosis. The technical challenges associated with animal models include strain-specific and diet-specific effects, differences in the absorption and distribution of carotenoids, and differences in the interactions of carotenoids with other antioxidants. Despite the problems associated with extrapolating from animal models to humans, the understanding and development of various animal models may provide useful information regarding the protective effects of carotenoids against lung carcinogenesis.     

类胡萝卜素生物合成相关基因的克隆及其遗传工程的研究进展

类胡萝卜素具有重要的生物学功能,尤其对人体健康有着更重要的作用,近年来一直是研究的热点。综述了类胡萝卜素生物合成途径及相关基因的分离,以及运用这些基因提高微生物和植物中类胡萝卜素含量的遗传工程研究进展。     

Antioxidant activity of carotenoids

Carotenoids are pigments which play a major role in the protection of plants against photooxidative processes. They are efficient antioxidants scavenging singlet molecular oxygen and peroxyl radicals. In the human organism, carotenoids are part of the antioxidant defense system. They interact synergistically with other antioxidants; mixtures of carotenoids are more effective than single compounds. According to their structure most carotenoids exhibit absorption maxima at around 450 nm. Filtering of blue light has been proposed as a mechanism protecting the macula lutea against photooxidative damage. There is increasing evidence from human studies that carotenoids protect the skin against photooxidative damage.     

Biological actions of carotenoids

Of 600 carotenoids from natural sources that have been characterized, fewer than 10% serve as precursors of vitamin A. Many dietary carotenoids, both with and without provitamin A activity, are found in the blood and tissues of humans. beta-Carotene, the most nutritionally active carotenoid, comprises 15-30% of total serum carotenoids. Vitamin A is formed primarily by the oxygen-dependent central cleavage of beta-carotene and other provitamin A carotenoids. Several carotenoids show enhancement of the immune response, inhibition of mutagenesis, reduction of induced nuclear damage, and protection from various neoplastic events in cells, tissues, and whole animals. Carotenoids also protect against photo-induced tissue damage. Some carotenoids, including beta-carotene, quench highly reactive singlet oxygen under certain conditions and can block free radical-mediated reactions. In epidemiological studies, the intake of carotenoid-rich fruits and vegetables has been correlated with protection from some forms of cancer, particularly lung cancer. Similarly, serum beta-carotene levels have been associated with a decreased chance of developing lung cancer. It must be stressed, however, that these epidemiological associations do not show cause and effect. In this regard, long-term intervention trials with beta-carotene supplements are in progress. Whatever the results of these trials, carotenoids clearly show biological actions in animals distinct from their function as precursors of vitamin A.     

Occurrence and biosynthesis of carotenoids in phytoplankton

Naturally occurring carotenoids are important sources of antioxidants, anti-cancer compounds and anti-inflammatory agents and there is thus considerable market demand for their pharmaceutical applications. Carotenoids are widely distributed in marine and freshwater organisms including microalgae, phytoplankton, crustaceans and fish, as well as in terrestrial plants and birds. Recently, phytoplankton-derived carotenoids have received much attention due to their abundance, rapid rate of biosynthesis and unique composition. The carotenoids that accumulate in particular phytoplankton phyla are synthesized by specific enzymes and play unique physiological roles. This review focuses on studies related to the occurrence of carotenoids in different phytoplankton phyla and the molecular aspects of their biosynthesis. Recent biotechnological advances in the isolation and characterization of some representative carotenoid synthases in phytoplankton are also discussed.     

Genetic manipulation of carotenoid biosynthesis: strategies, problems and achievements

Carotenoids, some of which are provitamin A, have a range of diverse biological functions and actions, especially in relation to human health. For example, carotenoids are known to be crucial for normal vision and have been associated with reducing the risk of several degenerative diseases including cancer. The putative advantage of modifying and engineering the carotenoid biosynthetic pathways is obvious: to provide sources for the isolation of desired carotenoids or to generate food plants with increased carotenoid content. This article reviews the studies of carotenoid production in heterologous microorganisms and the engineering of crop plants using manipulated carotenoid biosynthesis.     

The biosynthesis and nutritional uses of carotenoids

Carotenoids are isoprenoid molecules that are widespread in nature and are typically seen as pigments in fruits, flowers, birds and crustacea. Animals are unable to synthesise carotenoids de novo, and rely upon the diet as a source of these compounds. Over recent years there has been considerable interest in dietary carotenoids with respect to their potential in alleviating age-related diseases in humans. This attention has been mirrored by significant advances in cloning most of the carotenoid genes and in the genetic manipulation of crop plants with the intention of increasing levels in the diet. The aim of this article is to review our current understanding of carotenoid formation, to explain the perceived benefits of carotenoids in the diet and review the efforts that have been made to increase carotenoids in certain crop plants.     

Production of phytoene, a carotenoid, and induction of connexin 26 in transgenic mice carrying the phytoene synthase gene crtB

Carotenoids have been recognized as chemopreventive agents against human diseases, such as cancer and cardiovascular disease. Mammalians utilize carotenoids supplied from their food since they are unable to perform the de novo synthesis of carotenoids. We previously created mammalian cultured cells producing phytoene, a type of carotenoid, and showed that these cells acquired resistance against oxidative stress and oncogenic transformation. In the present study, we established a transgenic mouse line, carrying the crtB gene encoding phytoene synthase, which could produce phytoene endogenously. It was found that connexin 26 was induced in these phytoene-producing mice. Since it is known that carotenoids enhance gap junctional communication by inducing the expression of connexin genes, the present data suggest that the induction of connexin 26 in phytoene-producing mice may play a role in controlling cell-to-cell communication. Phytoene-producing mice provide a useful system in which to investigate the in vivo function of the carotenoid phytoene.     

Progress in Microbial Carotenoids Production

Carotenoids are versatile isoprenoids pigments, play a vital role in the cellular system, starting from antioxidant to gene regulation. Carotenoids are widely used in food, nutraceuticals, and cosmetics owing to their vitamin A, antioxidant and anticancer activities. The demand of carotenoids in various sectors has triggered the research to explore a commercially viable and environmentally friendly production. This article presents a short review of progress in carotenoids production from microbial platforms.     

The role of carotenoids and their derivatives in mediating interactions between insects and their environment

Carotenoids are long conjugated isoprenoid molecules derived mainly from plants and microbial organisms. They are highly diverse, with over 700 identified structures, and are widespread in nature. In addition to their fundamental roles as light-harvesting molecules in photosynthesis, carotenoids serve a variety of functions including visual and colouring pigments, antioxidants and hormone precursors. Although the functions of carotenoids are relatively well studied in plants and vertebrates, studies are severely lacking in insect systems. There is a particular dearth of knowledge on how carotenoids move among trophic levels, influence insect multitrophic interactions and affect evolutionary outcomes. This review explores the known and potential roles that carotenoids and their derivatives have in mediating the ecological interaction of insects with their environment. Throughout the review, we highlight how the fundamental roles of carotenoids in insect physiology might be linked to ecological and evolutionary processes.     

Raman 'optical biopsy' of human breast cancer

Raman imaging (RI) is a novel method of medical diagnostics of human breast cancer and has a potential to become a routine optical biopsy. Up to date the present study is the most statistically reliable Raman analysis based on data of normal, benign, and cancerous breast tissues for 146 patients. This paper present the first Raman 'optical biopsy' images of the normal and cancerous breast tissue of the same patient. The results presented here demonstrate the ability of Raman spectroscopy to accurately characterize cancer tissue and distinguish between normal (noncancerous), and cancerous types. The results provide evidence that carotenoids and lipids composition of cancerous breast tissues differs significantly from that of the surrounding noncancerous breast tissue and may be a key factor responsible for mechanisms of carcinogenesis. We have found that fatty acid composition of the cancerous breast tissue is markedly different from that of the surrounding noncancerous breast tissue. The cancerous breast tissue seems to be dominated by the metabolism products of the arachidonic acid - derived cyclic eicosanoids catalyzed by cyclooxygenase, while the noncancerous breast tissue is dominated by monounsaturated oleic acid and its derivatives.     

利用基因工程改良植物类胡萝卜素的合成

类胡萝卜素(carotenoids)是植物体内存在的一类重要天然色素物质的总称,其生物功能广泛.类胡萝卜素是人类饮食结构中重要的组成部分,并且在医药、化妆品及食品与饲料工业等方面扮演着重要的角色.类胡萝卜素还是一些维生素合成的前体,具有多种保健功能,可以提高人体免疫力,并具有抗癌的功效.目前有大量关于提高植物体内类胡萝卜素含量及定向改变其种类的研究,对类胡萝卜素代谢途径及其调控的理解是这些研究的基础.主要阐述植物天然类胡萝卜素的生物合成及利用基因工程对类胡萝卜素改良的研究进展.     

Thermotropic phase behaviour of alpha-dipalmitoylphosphatidylcholine multibilayers is influenced to various extents by carotenoids containing different structural features--evidence from differential scanning calorimetry

Carotenoids are the effective modulators of physical properties of model and natural membranes. To demonstrate the relationship between the structure of carotenoids and their effect on the molecular dynamics of membranes, we have investigated the influence of five structurally different carotenoids: beta-carotene, lycopene, lutein, violaxanthin, zeaxanthin and additionally carotane--a fully saturated derivative of beta-carotene, on thermotropic phase behaviour of dipalmitoylphosphatidylcholine (DPPC) multilamellar vesicles by means of differential scanning calorimetry (DSC). The results obtained indicate that the carotenoids used modulated the thermotropic properties of multibilayers to various extents, broadening the pretransition and the main phase transition peaks and shifting them to lower temperatures. Pronounced decrease of pretransition enthalpy (DeltaH(p)) proves that carotenoids very strongly alter the membrane properties in its gel phase. Comparison of the influence of several carotenoids shows that a rigid, polyisoprenoid chain plays a basic role in altering the thermotropic properties of such membranes and the presence of rings without oxygen-containing groups has a minor significance for the observed interactions. Carotenoids containing epoxy and/or hydroxy groups attached to their rings modify the thermotropic phase behaviour of DPPC multilamellar vesicles stronger than carotenes--a result of their orientation in the DPPC bilayer.     

The role of mutants in the search for the photoreceptor for phototropism in higher plants

Early attempts to identify the chromophore of the photoreceptor for phototropism are reviewed. Carotenoids and flavins were the principal candidates, but studies with grass coleoptiles devoid of carotenoids suggest that at least in these organs carotenoids are most unlikely to play that role. The status of characterization of a gene for a putative photoreceptor protein is also reviewed. As the action spectrum for phototropism resembles the absorption spectrum of a flavoprotein, flavoproteins are attractive candidates at present, especially since the CRY1 photoreceptor in Arabidopsis thaliana that mediates blue light-dependent hypocotyl growth suppression has flavin adenine dinucleotide as one of its two chromophores. As the second chromophore appears to be pterin, pterins should not be ruled out as candidate chromophores for the photoreceptor for phototropism.     

Carotenoids: recent progress, problems and prospects

1. This is a review of the current state of research on the structure and functions of carotenoids, a common group of natural pigments. 2. Discussed in this paper are recent advances in carotenoid studies and problems that still await elucidation. 3. A new natural nomenclature is proposed to rationalize investigation of biological functions of carotenoids. 4. Data included in the paper are taken from the book, "Biological Functions of Carotenoids" (Karnaukhov, 1988).     

Metabolic engineering for the microbial production of carotenoids and related products with a focus on the rare C50 carotenoids

Carotenoids, a subfamily of terpenoids, are yellow- to red-colored pigments synthesized by plants, fungi, algae, and bacteria. They are ubiquitous in nature and take over crucial roles in many biological processes as for example photosynthesis, vision, and the quenching of free radicals and singlet oxygen. Due to their color and their potential beneficial effects on human health, carotenoids receive increasing attention. Carotenoids can be classified due to the length of their carbon backbone. Most carotenoids have a C40 backbone, but also C30 and C50 carotenoids are known. All carotenoids are derived from isopentenyl pyrophosphate (IPP) as a common precursor. Pathways leading to IPP as well as metabolic engineering of IPP synthesis and C40 carotenoid production have been reviewed expertly elsewhere. Since C50 carotenoids are synthesized from the C40 carotenoid lycopene, we will summarize common strategies for optimizing lycopene production and we will focus our review on the characteristics, biosynthesis, glycosylation, and overproduction of C50 carotenoids.     

天然类胡萝卜素生物合成与生物技术应用

类胡萝卜素是重要天然食用色素族群之一,它不仅可为食品添色,还具有较高营养保健价值。类胡萝卜素广泛存在于高等植物、藻类、少数微生物和部分动物体内,但不同生物在合成途径细节及所积累的类胡萝卜素种类方面存在较大的差异。通过优化培养条件、转基因和水解酶辅助提取等生物技术手段提高了类胡萝卜素产量,降低了生产成本,从而使天然类胡萝卜素制品得到更广泛的应用。