Chemistry Zone

Carotenoids

Carotenoids
Carotenoids are familiar to all of us through the orange-red colours of popular foods like oranges, tomatoes and carrots, and the yellow colours of many flowers.
They are also added as colorants to many manufactured foods, drinks and animal feeds, either in the form of natural extracts (e.g annatto) or as pure compounds manufactured by chemical synthesis. The production of carotenoids by biotechnology is of increasing interest. Carotenoids are essential to plants for photosynthesis, acting in light-harvesting and, especially, in protection against destructive photooxidation. Without carotenoids photosynthesis in an oxygenic atmosphere would be impossible.
But carotenoids are not simply pigments of terrestrial plants. They occur widely in bacteria, fungi and algae, where they can be useful taxonomic markers. The production of carotenoids in seaweed runs to hundreds of million tons per year.
Some animals use carotenoids for coloration, especially birds (yellow and red feathers), fish (g.g. goldfish and salmon) and a wide variety of invertebrate animals, where complexation with protein may modify their colour to blue, geen or purple.
Carotenoids are important factors in human health. The essential role of beta-carotene and others as the main dietary source of vitamin A has been known for many years. More recently, protective effects of carotenoids against serious disorders such as cancer, heart disease and degenerative eye disease have been recognized, and have stimulated intensive resarch into the role of carotenoids as antioxidants and as regulators of the immune response system.
Currents carotenoid research encompasses a wide veriety of fields and interests including plant physiology, food science, environmental science, taxonomy, industrial chemical synthesis, biotechnology and medical research. All the work must be based on a solid foundaation of carotenoid chemistry and reliable methods for handling and analysing these rather unsatble substances.
CAROTENOIDS?
Of the various classes of pigments in Nature the carotenoids are among the mostwidespread and important ones, especially due to their most varied functions.In 1831 Wackenroder isolated carotene from carrots and in 1837 Berzelius namedthe yellow pigments from autumn leaves xanthophylls. This marks the beginning ofcarotenoid research and since then continuous developments have taken place.Because of their ubiquitous occurrence, different functions (see below), and interestingproperties carotenoids are the subject of interdisciplinary research in chemistry, bio-chemistry, biology, medicine, physics, and many other branches of science.

Carotenoids can help you to:
Minimize the risk for certain types of cancer;
Reduce the risk for CVD's;
Help to avoid catarracts.

They further:
Have an important role in photosynthesis;
Are powerful antioxidants in Nature;
Are used to attract animals (and humans) with their color.

OCCURRENCE
As already mentioned, the carotenoids are a class of natural pigments that is very widespread and it was demonstrated that they occur in all the three domains of life, i.e. in the eubacteria, the archea and in the eucarya. A rich source for carotenoids are the algae and more than 100 carotenoids have been isolated and characterized from these organisms. For humans the most important source for carotenoids are plants, where often the brilliant colors of the carotenoids are masked by chlorophyll, e.g. in green leaves. The carotenoids are responsible for the beautiful colors of many fruits (pine-apple, citrus fruits, tomatoes, paprika, rose hips) and flowers (Eschscholtzia, Narcissus), as well as the colors of many birds (flamingo, cock of rock, ibis, canary), insects (lady bird), and marine animals (crustaceans, salmon). Normally carotenoids occur in low concentrations, but this varies enormously from one source to another. The total carotenoid production in nature has been estimated at about 100'000'000 tons a year. Recently it was demonstrated by the analysis of serum and human breast milk that up to 50 dietary carotenoids from fruits and vegetables may be absorbed and metabolized by humans.
Carotenoids are a class of hydrocarbons (carotenes) and their oxygenated derivatives (xanthophylls). They consist of eight isoprenoid units joined in such a manner that the arrangement of isoprenoid units is reversed at the center of the molecule so that the two central methyl groups are in a 1,6-position relationship and the remaining nonterminal methyl groups are in a 1,5-position relationship. All carotenoids may be formally derived from the acyclic C40H56 structure (I) (Fig. 1), having a long central chain of conjugated double bonds, by (I) hydrogenation, (2) dehydrogenation, (3) cyclization, or (4) oxidation, or any combination of these processes. The class also includes compounds that arise from certain rearrangements or degradations of the carbon skeleton (I), provided that the two central methyl groups are retained.
About 600 carotenoids have been isolated from natural sources; they are listed with their trivial and semisystematic names in Key to Carotenoids (Pfander, 1987) and in the Appendix of Carotenoids, Volume 1A (Kull & Pfander 1995) which also includes literature references for their spectroscopic and other properties. It must be pointed out, however, that for many of the carotenoids listed the structure (this term includes the stereochemistry) is still uncertain and in all these cases a reisolation, followed by structural elucidation with all the modern spectroscopic methods (especially high resolution nuclear magnetic resonance (NMR) spectroscopy) is absolutely necessary. About 370 of the naturally occurring carotenoids are chiral, bearing from one to five asymmetric carbon atoms, and in most cases one carotenoid occurs only in one configuration in Nature.

Rules for the nomenclature of carotenoids (semisystematic names) have been published by the International Union of Pure and Applied Chemistry (IUPAC) and IUPAC-International Union of Biochemists (IUB) Commissions on Nomenclature (1975). For the most common carotenoids trivial names are normally used. If these trivial names are used in a paper, the semisystematic name should always be given, in parentheses or in a footnote, at the first mention. All specific names are based on the stem name carotene, which corresponds to the structure and numbering in II (Fig. 2).

The name of a specific compound is constructed by adding two Greek letters as prefixes (Figure 3) to the stem name carotene; the Greek letter prefixes are cited in alphabetical order.

The oxygenated carotenoids (xanthophylls) are named according to the usual rules of organic chemical nomenclature. The functions most frequently observed are hydroxy, methoxy, carboxy, oxo, and epoxy. In addition, carotenoids with triple bonds are also known. Important and characteristic carotenoids (Fig. 4) are lycopene (gamma,gamma-carotene) (I), beta-carotene (beta,beta-carotene) (III), alpha-carotene ((6’R)-beta,epsilon-carotene) (IV), beta-cryptoxanthin ((3R)-beta,beta-caroten-3-ol) (V), zeaxanthin ((3R,3'R)-beta,beta carotene-3,3'-diol) (VI), lutein ("xanthophyll", (3R,3'R,6'R)-beta,epsilon -carotene-3,3'-diol) (VII), neoxanthin ((3S,5R,6R,3'S,5'R,6'S)-5',6'-epoxy-6,7-didehydro-5,6,S',6'-tetrahydro-beta,beta-carotene-3,5,3'-triol) (VIII), violaxanthin ((3S,5R,6R,3’S,5'R,6'S)-5,6,5',6'-diepoxy-5,6,5',6'-tetrahydro-beta,beta-carotene-3,3'-diol) (IX), fucoxanthin ((3S,5R,6S,3'S,5'R,6'R)-5,6-epoxy-3,3',5'-trihydroxy-6',7'-didehydro-5,6,7,8,5',6'-hexahydro-beta,beta-caroten-8-one 3'-acetate) (X), canthaxanthin (beta,beta-carotene-4,4'-dione) (XI), and astaxanthin ((3S,3'S)-3,3'-dihydroxy-beta,beta-carotene-4,4'-dione) (XII).

Derivatives in which the carbon skeleton has been shortened by the formal removal of fragments from one or both ends of a carotenoid are named apo- and diapocarotenoids, respectively, e.g. beta-apo-8'-carotenal (8'-apo-beta-caroten-8'-al) (XIII). Other structural variations are encountered in the norcarotenoids, in which one or more carbon atoms have been eliminated from within the typical C40-skeleton. A prominent example is the C37-skeleton of peridinin ((3S,5R,6R,3’S,5’R,6’R)-epoxy-3,5,3’-trihydroxy-6,7-didehydro-5,6,5’,6’-tetrahydro-10,11,20-trinor-beta,beta-caroten-19’,11’-olide 3-acetate) (XIV) characteristic of diatoms.

This cis-trans or (E/Z)-isomerism of the carbon-carbon double bonds is another interesting feature of the stereochemistry of the carotenoids, because it was demonstrated that the (E/Z)-isomers may have different biological properties. The literature in this field is extensive: the first comprehensive review of the cis-trans isomerism of carotenoids and vitamin A was published in 1962 (Zechmeister, 1962). According to the number of double bonds a great number of (E/Z)-isomers exist for each carotenoid, e.g. 1056 for lycopene (I) and 272 for b-carotene (III). In view of the (E/Z)-isomerism the double bonds of the polyene chain can be divided into two groups: (I) double bonds with no steric hindrance of the (Z)-isomer (central 15,15'-double bond and the double bonds bearing a methyl group, such as the 9-, 9'-, 13-, and 13'-double bonds) and (2) double bonds with steric hindrance (7-, 7'-, 11-, and 11’-double bonds). Although isomers with sterically hindered (Z)-double bonds are known ((11Z)-retinal) the number of possible (Z)-isomers is in practice reduced considerably, e.g., for lycopene (I) to 72. Normally carotenoids occur in Nature as the (all-E)-isomer; however, exceptions are known, such as the (15Z)-phytoene isolated from carrots, tomatoes, and other organisms. On the other hand, some carotenoids undergo isomerization very easily during workup; therefore many (Z)-isomers that are described in the literature as natural products are artifacts. For experimental work it must be kept in mind that (E/Z)-isomerization may occur when a carotenoid is kept in solution. Normally the percentage of the (Z)-isomers is rather low, but it is enhanced at higher temperature. Furthermore, the formation of (Z)-isomers is increased by exposure to light.

Carotenoids are synthesized in Nature by plants and many microorganisms. Animals can metabolize carotenoids in a characteristic manner, but they are not able to synthesize carotenoids.
Carotenoids, being terpenoids, are synthesized from the basic C5-terpenoid precursor, isopentenyl diphosphate (IPP) (XVII) (Fig.1). This compound is converted to geranylgeranyl diphosphate (C20) (XVIII). The dimerization of XVIII leads to phytoene (7,8,11,12,7’,8’,11’,12’-octahydro-gamma,gamma-carotene) (XIX) and the stepwise dehydrogenation via phytofluene (15Z,7,8,11,12,7’,8’-hexahydro-gamma,gamma-carotene (XX), zeta-carotene (7,8,7’,8’-tetrahydro-gamma,gamma-carotene) (XXI), and neurosporene (7,8-dihydro-gamma,gamma-carotene) (XXII) gives lycopene (I). Subsequent cyclizations, dehydrogenations, oxidations, etc., lead to the individual naturally occurring carotenoids, but little is known about the biochemistry of the many interesting final structural modifications that give rise to the hundreds of diverse natural carotenoids.

There are now exciting prospects for rapid progress through the application of molecular genetics techniques in combination with other biochemical and chemical approaches. The benefits of this are not purely academic. The industrial production of natural carotenoids through microbial biotechnology is already established and expanding, mainly through the exploitation of some microalgae (particularly Dunaliella) which can synthesize large amount of carotenoid.