SERIAL REVIEWS I

Structure and properties of carotenoids in relation to

function
GEORGE BRITFON’
Department of Biochemistry, University of Liverpool. Liverpool, United Kingdom

branes, and thus affecting molecular processes asso-

Essentially all carotenoids, which are widespread in ciated with these membranes, may be an important
nature, possess certain common chemical features: a aspect of their possible beneficial effects on human
polyisoprenoid structure, a long conjugated chain of health.-Britton, G. Structure and properties of ca-
double bonds in the central portion of the molecule, rotenoids in relation to function. FASEB J. 9, 1551-
and near symmetry aroutid the central double bond. 1558 (1995)
This basic structure can be modified in a variety of
ways, most prominently by cyclization of the end Key Words: light absorption . lipid peroxidaiion . carotenoid-pro-

groups and by the imitroduction of oxygen functions, to !ein in/era c/ions membranes . free-radical rer, c/was
yield a large faniily of >600 compounds, exclusive of
THE CAROTENOIDS ARE NOT JUST “another group of tiatu-
cis/trans isomers. They perform important functions in
ral pigments.” They are substances witil vety special and
nature, including light-harvesting, photoprotection,
remarkable properties that no other groups of substamices
protective and sex-related coloration patterns in niany
possess and that form the basis of their marty, varied
animal species, and as precursors of vitamin A in ver-
functions atid actions in all kimids of livimig organisms.
tebrates. They may serve protective roles as well
Often traditionally thought of as plant pigmemits, the ca-
against age-related diseases imi humans as part of a
rotemioids have a nluch wider distribution and occur ex-
complex antioxidant network within cells. In this open-
tensively also in animals and mnicroorganisms. Tile
ing review, emphasis is placed on the close relation-
striking natural colors that are due to carotenoids-e.g.,
ship between the physicochemical properties of
in yellow, orange, amid red flowers amid fruit-are familiar
carotemioids and their functions and actions in nature.
to all of us, but othei’, less obvious roles make carote-
James A. Olson, Coordinating Editor
noids essential components in oxygenic photosymitlietic
ABSTRACT The basic principles of structure, organisms. Without carotenoids, photosynthesis amid all
stereochemistry, and nomenclature of carotenoids life in an oxygen atmosl)liel’e would be impossible. Ca-
are described and the relationships between struc- rotenoids have recemitly heemi implicated as well in tile

ture and the chemical and physical properties on prevention of or protection against serious huniami health
which all the varied biological functions and actions disordet’s such as cancel’ amid heart disease. Thus, these
of carotenoids depend are discussed. The conjugated substances are clearly of major inlportance in biology.
polyene chromophore determines not only the light The natural functiomis arid actions of carotenoids obvi-
absorption properties, and hence color, but also the ously are determined by the physical and chemical prop-
photochemical properties of the molecule and con- em’ties of the molecules, and these properties are defined
sequent light-harvesting and photoprotective action. by the molecular structure. Fit’st, tue overall molecular

The polyene chain is also the feature mainly respon- geometry (size, shape, presence of functional groups) is
sible for the chemical reactivity of caroteitoids to- vital for ensuring that the carotenoid fits imito cellular and
ward oxidizing agents and free radicals, and hence subcellular structures in the correct location amid ot’iemita-
for any antioxidant role. In vivo, carotenoids are lion to allow it to functiomi efficiently. Secomicl, the conju-
found in precise locations and orientations in s,ihcel- gated double bond system (letermimies the photochemical
lular structures, and their chemical and physical properties and chemical reactivity that forni the basis of
properties are strongly influenced by other mole- these functions. In addition, specific imiteractions with

cules iii their vicinity, especially proteins and mem- other molecules in the immediate vicinity are crucial for
brane lipids. In turn, the carotenoids influence the correct functioning.
properties of these subcellular structures. Structural
features such as size, shape, and polarity are essential
Semid corrcsi)onclemio:e ammo!
mt’l)nmntmetluests tim Dr. Britttumm, at: Depart-
determinants of the ability of a carotenoid to fit
mt’nl of Biochemistry, Umiiversily of Livt’rpnol, P.O. Box 147, Lit t’mpooi
correctly into its molecular environment to allow it
L69 3BX. United Kingclomn,
to function. A role for carotenoids in modifying 2Abhreviaiions: AIBN, 2,2’-mzti-bis-isohtmtvmomiitmiIe; AMVN. 2,2’-0mzo-
structure, properties, and stability of cell mem- bis (2.4-dimethiylvuleromiitnile).

0892-6638/95/0009-i 551/$01.50. © FASEB 1551

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 SERIAL REVIEW

The main objective of this article is to describe the especially iii biological work, to use the well-known triv-
structures and properties of carotenoids amid to use this ial names even though genel’ally they convey no itiforma-
information as a basis for understandimig how carotemloids tion about the structure of the cam’otemioid. A
mnay function and act in biological systems. senlisystematic scheme has therefore been devised that
allows any carotenoid to be named unambiguously and in
a way that defines and describes its structure. In essence,
CAROTENOID STRUCTURES AND
all specific names are based on the stem name “caro-
NOMENCLATURE
tetle,” preceded by tile Greek-letter prefixes tllat desig-
More than 600 differemit carotetioids have been isolated hate the two end groups; the seven end groups are
fm’om natural sources and characterized (1, 2). For the llustrated in Fig. lB.
newcomer to the field, the prospect of having to assimi- For clarity amid to avoid confusion, the use of both end-
late such a mnass of detailed cheniical imiformation is group prefixes for a carotene is now recommended (3).
dautititig. Fortunately, although these are all different Thus, for example, “3-carotene” is now more correctly
structures, for mamiy purps they cati be considered as referred to as p43-carotene, a-carotene as ,E-carotene,
variatiomis omi a structural theme and, imi terms oi many of etc. Changes in hydrogenation level and the presence of
the basic chemical and physical properties, the carote- oxygen-contaimlimig substituemits are indicated by the
noids niay he cotlSidel’e(l as a gt’oup. standard prefixes and suffixes used in organic chemistiy.
Thus, the biosynthetic precursor phytoene becomes
Basic structure
7,8,11 ,12,7’,8’,1 1’,12’-octahydm’o-,-carotene, amid zeax-
The carotenoids are isoprenoid compounds, biosynthe- ant hi ii is ,-carotemie-3,3’-d iol. Many nat ural carote-
sized by tail-to-tail linkage of two C20 geranylgeranyl noids are optically active, i.e., chiral compounds;
diphiosphate molecules. This prodttces the parent C10 ciiit’ality is indicated by the conventional R,S system.
carbon skeleton fi’om which all the imidividual variations The IUPAC-IUB rules are given in full iti an IUPAC
are derived. In Fig. 1A, this basic structure is illustrated publication (4) and in volume 1A of the new series, Ca-
by lycopene atid ,-carotene; the carotenoid numbering rotenoids (5).
scheme is also shown. This skeleton can be modified 1) Some carotenoidshave a structure consisting of fewer
by cyclization at one end or both ends of thie molecule to thami 40 carbon atoms and dem’ived formally by loss of part
give the seven different end groups (illustrated in of the C40 skeleton. These compounds are referred to as
Fig. 1B), 2) by changes in hydi’ogenation level, amid 3) by apocarotenoids when carbon atoms have been lost from
addition of oxygemi-comitai ni ng functional groups. Carote- the ends of the molecule or as norcarotenoids when carb-
noids that contain one or more oxygen functions are on atoms have heemi lost formally fm’om within the chain.
known as xanthophylls, the parent hydrocarbons as caro-
The polyene chain
tenes.
The most striking and characteristic feature of the carote-
Nomenclature
tioid structure is the long system of alternating double
Traditionally, carotenoids have been given trivial names and single bonds that forms the centm’al part of the mole-
derived usually from the biological source from which tile cule. This constitutes a conjugated system in which tue
carotenoid was first isolated. It is still common practice, it-electt’ons are effectively delocalized over the entire
17 16 17 16
A7 18 tO 20 18
#{163}35LR 2 2><r(R

Lycopene
16 2 4 6 4518

p C
I7JJ3

16
17 16 16 CH2R
-carotene 17 1 :i 18

18 2L.,,,,J4 5 18

I K

17.

Figure 1. A) Basic structure and nunibening scheme of au acydie

carotenoid (lycopene) an a dicyelic carotenoid (,J-carotene). B) The 18
seven different end groups found in natural carotenoids, x

1552 Vol. 9 December 1995 The EASER Journal BRITFON

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 SERIAL REVIEW

length of the polyene chain. It is this feature that gives double bonds, however, a cis configuration t’esults ill ma-
the carotenoids as a group their distinctive molecular jor steric interference between a methyl group and a Ily-
shape, chemical reactivity, and light-absorbing proper- drogen atom (5) (Fig. 2B). Isomers containing such
ties. sterically hindered double bonds are hard to form and are
rarely encountered in nature, e.g., 7-cis- and 11-cis-3-
Stereochemistry
carotemie.
Because of isomerism around C=C double bonds, differ-
Gonformat ion
ent configurations are possible. These are distinctly dif-
ferent molecular structures that can be isolated as Although, primiciple,
in a carotenoid with a defined
separate compounds. In addition, rotation is theoretically cis/trans configurationcart adopt a very large miumber of
possible about any C-C single bond imithe polyene chain, shapes, in practice the carotenoid will exist in a particu-
so the carotenoids can, in principle, adopt an enormous lar preferred, low-energy conformation.
number of shapes or conformations.
The polyene chain. By far the most stable form of the con-
Configuration: geometrical isomers jugated polyene chain is a linear, extended conformatioti.
Two major factors are responsible for this. First, a comiju-
In principle, each double bond in the polyene chain of a
gated system is greatly stabilized when the double bonds
carotenoid can exist in two forms (configurations), desig-
are coplanar. Second, steric himidm’ance is smallest whemi
nated trans or cis, depending on the disposition of substi-
each C-C single bond is in the s-trans conformatiomi
tuent groups, specifically those that constitute a
(equivalent to a trans double-bond configuration, Fig. 2C).
continuation of the polyene chaiti, about that double bond
X-Ray crystallographic data reveal that carotemioids are
(5) (Fig. 2A). [In current chemical usage, the configiira-
essentially extended linear molecules with omily a slight
tion about a double bond is designated E or Z. In carote-
5-shaped distortion to relieve stet’ic tension (6).
noids E and Z are usually equivalent to trans and cis,
respectively, although there are some exceptiomis.] This The ring-chain junction. Because of theoretical free rota-
gives rise to a large number of theoi’etically possible tion about the C-6,7 single bomid in carotenoids with cyclic
monocis and polycis isomers. In reality, only a few of end groups, in principle there can be an imif’inite number of
these geometrical isomers are encountered in nature. Tue possible angles of twisting between the ring and the main
presence of a cis double bond creates greater steric hin- polyene chain. In the n-ring carotenoids, the C-5,6 double
drance between nearby hydrogen atoms and/or methyl bond is formally conjugated with the polyene chaimi, so tilat
groups, so that cis isomers are generally less stable ther- coplanarity of the ring and chain double bonds should be
modynamically than the trans form. Most carotenoids, favored. There are two extreme structures, 6-s-cis and 6-s-
therefore, occur in nature pi’edominantly or entirely in the trans (Fig. 2D), that allow such coplanarity, but these
all-trans form. With some double bonds, i.e., those that would generate considerable steric crowding (5). It is now
bear three substituents and also the disubstituted C- kmlown that the preferred cotiformation is 6-s-cis, but this
15,15’ double bond, the steric hindrance is small so that is distorted approximately 40#{176}
from planarity to relieve
isomers with cis double bonds in these positions are rela- steric interference between the C-5 methyl substituent on
tively easily formed and relatively stable (e.g., 9-cis-, 13- the l’ing and the C-8 hydrogen atom of the chain (7). With
cis-, and 15-cis-f34-carotenes). With other disttbstituted tue E-rimtg, the cyclic double bond (C-4,5)isnot in conju-

H\ /R2 IsS R2 H H
\ /
/O==C\ c=c \
c==c
/ \ / c-c,
Rm H R1/ \ H
R( \ 2Rt /
\ R2
A Irons
C’s
C s-cis S - trans

B ‘unhindered’ ‘hindered’ D 6 - s - cis 6 -s-trans

Figure 2. A) cis and trans double bonds in cam’otenoids. B) Stenically “hindered” and “unhindered” cis double bonds in the pol’ene chain of carotenokJs.
C) The s-cis and s-trans conformations of single bonds in the polyene chain. D) The 6-s-cit and 6-s-trans conformatiomis of n-ring carotenoids,

STRUCTURE AND PROPERTIES OF CAROTENOIDS 1553

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 SERIAL REVIEW

gation, so that relief of steric crowding becomes the only in the idetitification of carotenoids, is developed more
major determinant of the preferred ring-chain conforma- fully elsewhere (8).
tion. But coloration is not tile sole function of carotenoids.
The ring-chain conformatiomi, together with the shape They have distinctive photochemical properties that form
of tile ring itself-normally a chair or half-chair confor- the basis of other, even more impol’tant functions (9). The
mation determnined by the presence of functional origin of these photocheniical Properties lies in the iispo-
gm’oups-establish the effective bulk of the end group. sition of the low-lying excited! energy states (both singlet
and triplet) of the carotenoids. The characteristic strong
absorption of light in the visible region is now attributed
PROPERTIES to a stm’ongly allowed transitionfrom the ground state So
General properties: size, shape, solubihity to the secomid singlet excited state, S2 (1’Bu). The energy
levels of this excited state, and of the somewhat lower
The cat’otenoids as a group are extremely hiydrophobic first excited state Sj (l’Ag) that can be formed from it by
molecules with little or no solubility in water. They are ititernal conversion, lie close to but above those of chlo-
thus expected to be restricted to hydrophobic areas in the rophiyll, so that singlet-singlet energy transfercan take
cell, such as the inner core of membranes, except wheti place from excited carotenoid to generate the excited sin-
associatiomi with protein allows theni access to an aqueous glet state S1 of chlorophyll, whichi is active in photosyn-
emivironment. (See section on Properties atid Molecular thesis (9).
Interactions of Carotenoids in vivo.) Polar functional Direct formation of the carotenoid triplet state (Ii)
groups obviously alter tile polarity of carotenoids and af- frotn the excited sitiglet states S2 or Si via singlet-triplet
fect their interactions with other molecules. imitersystem crossitig is not favored. Its formation by en-
The overall size and shape of the mnolecule are ex- ergy transfer from other triplet-state molecules acting as
tremely important imi relation to the properties of a carote- photosetisitizers can be very efficient, however, provided
noid and, hence, to functiomi. All colored carotenoids in the cat’otenoid contains more than seven conjugated dou-
the all-trans configuration have au extended conjugated ble botlds, because the carotenoid triplet-state energy is
double-bond system and are linear, rigid molecules. Tim low (9).Transfer of energy from triplet-state chlorophyll
cis-isomers, however, are mio longet’ simple linear mole- or other porphyrimis to carotenoids occurs much more
cules. Their overall shape differs substantially from that readhilythamithe alternative energy transfer to oxygen to
of the all-trans form, so their ability to fit itito subcellular form the hiighly reactive and destructive singlet oxygen
structures may be greatly altered. The temidetmy of cis-iso- 102. Carotemloids can also accept excitation energy from
niers to crystallize or aggregate is usually much less; 102 if any should be fornied. The triplet-state carotenoid
tllerefore cis-isomers may be more readily solubilized, ab- is of such low energy that it is unable to generate other
sorbed, amid transpom’ted than their all-trans counterparts. species by energy transfer aild it dissipates its excitation
The shape and size of the emid groups are also impot’- energy harmlessly to its surroundings. This allows
tant factors. Acychic cat’otemioidls such as lycopene are es- carotetie to pt’otect photosynthietic reaction-center com-
sentially long, hineam’ mnolecules with flexible end groups. plexes agaimist damage thiat would be caused by a
Cychizatioti shortens the overall length of the molecule combination of light and oxygen (9) amid to provide an ef-
and increases the effective bulk of the end groups and fective treatmetit for humaii patients suffering from
the space they occupy. The effective bulk depends on the etytht’opoietic protoporphyria, a condition in which free
preferred conformatiomi, as detertnined by steric factors porphiyrimis accumulate in the skin and sensitize the for-
and the presence of subslituent groups, and can be al- mation of ‘02 (10).
tered sigmiificantly by apparently small structural changes For efficient energy transfer imivolving either singlet or
such as epoxidation-deepoxidatiomi. triplet states, tile molecules concerned must l)e held in
close proximity and in tile correct orientation by specific
Light absorption and photochemical properties
interactions withl other niolecules such as, for example,
The absorption
of light energy by an orgatlic molecule proteins (9) (see section on Pioperties amid Molecular In-
produces a llighler-eflergy excited state of that molecule.
tem’aclions of Carotenoids in vivo).
In the case of carotenoids, the relevamit transition is a
y* transition, in which otie of the botiditig IL-elections Cheniical properties
of the comijugated double-bomid systeni is pronioted to a
previously unoccupied ic antibondiiig orbital. The it- The fundaniemital chemistt’y of cat’otemioid radicals amid of
electromis are highly delocalized and the excited state is the reactions of carotenoids with oxidizing agents, peroxy
of comparatively low energy, so the energy required to ra(hicals, etc., is important for evaluating the proposed ac-
bring about the transition is relatively small amid corre- tions of carotenoids as antioxidants, but it is not well un-
sponds to light in the visible region in the wavelength dherstood. The strategy adopted here is not to survey the
range of 400-500 nmii. Carotenoids are therefore intensely literature that deals with carotenoids as amltioxidants, but
colored yellow, orange, or red. The relationship betweemi to consider the pt’operties of the carotenoicis amid their
chromophiore atidlight-absorption
properties,widely used t’adicals and the chemistiy of their reactions with oxidiz-

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 SERIAL REVIEW

ing agents as a basis for assessing whether an antioxidant system that is susceptible to attack by electrophiilic re-
or other chemical role in vivo is feasible. agents, is responsible for the imistahility of carotemtoids to-
ward oxidation, and is tile important feature of the
Carotenoid radicals tnolecule in relation to free-radical chemistry.
Many of the important oxidations are free-radical reac- Pure carotenoids, even in the crystalline state, are sus-
tions, so a consideration of the generation and properties ceptible after isolation to oxidation and may be broken
of carotenoid radicals and of carbon-centred radicals de- down rapidly if samples are stored in tile pt’esence of
rived from carotenoids by addition of other species is even traces of oxygen. In vivo, tile carotenoids are usually
relevant (11). The carotenoid radicals are very short-lived stabilized to a considerable degree by proteins and other
species. Some information has been obtained about thiem molecules in their immediate vicinity. Even in vivo, how-
by the application of radiation techniques, particularly ever, the carotenoids are still susceptible to oxidative
pulse radiolysis. In primiciple, carotenoid radicals can be damage if they become exposed to oxidizing species or
generated in different ways. free radicals that may be generated. Tile usual imidication
of carotenoid breakdown is bleaching, i.e., loss of color
Oxidation. Oxidizing radicals with high redox potential cati
due to breaking of the chromophore.
remove one electron from the carotenoid molecule to give
Oxidative degradation was used for many years in the
the radical cation.
classical chemistry that led to the elucidation of carote-
noid structures (13). Comitt’olled chemical reactions were
CAR-e -+ cAR:
used to break variouscarbon-carbon double bonds imitue
e.g., CAR+R: - CAR: + R polyene chaiti to generate apocarotenals and apocaro-
tenones as well as small fragments aI’isimig from complete
Reduction. The aclditiomi of one electron to the cat’otenoid breakdown.
molecule would give the radical anion. Oxidhative breakdowmi is also caused by free-radical re-
actions; indeed, rapid bleaching by hydt’oxyl radicais is
CAR+e -* CAR. well known (14). Recent work iti this area hias concen-
trated on the reactions with pet’oxy t’adicals generated in
Hydrogen abstraction. The abstraction of a hiydrogemi atom some cases by pulse radiolysis. e.g., by the CCI;100
H from a sattirated carbon atom in a position allylic to the radical (15), but mostly by use of so-called azo-initiators
polyene chain can generate a resonance-stabilized neutm’al such as 2,2’-azo-bis-isohutyronitrile (AIBN) and 2,2’-azo-
radical by homolytic cleavage of a C-H bond. For instance, bis(2,4-dimethylvaleronitrile) (AMVN). Comitrolled diet’-
if ma! decomposition of these substamices generates free
radicals thiat, iti the presence of oxygen, give rise to the
CAR=X-H, cort’esponchimig peroxy radicals (16). These imi turn react
thenX-H+R--4X-I-RH with the carotenoids. A wide variety of products have
been detected in these studies. Most seem to be apocaro-
Addition. The addition of a radical species such as a per- tenals ot’ apocarotemlones of various chain letigthis pro-
oxy radical ROO or tile hydroxyl radical HO’ to the (huced by cleavage of any (hoUble bond iii the pohyene
polyene chain could gemieratea cam’otenoid-aciduct radical, chaiml; epoxides are also commonly foumid (17, 18).
e.g., Sitiiilar chemical reactions also occur betweemi cam’ote-
noids and singlet oxygen, andh agaimi gemierate apocam’o-
CAR + ROO-CAR - OOR temials and apocat’otenomles as the major I)t’o(1u(ts. The
niechiamiism may i)e diffem’ent, howevem’, and may involve
In the carotenoid t’adicals, the unpaired electromi is the addition of ‘02 to a double bond to form a labile di-
highly delocalized over the conjugated polyene cht’omo- oxetamie, which is then cleaved to give the cort’espomidling
phore. This has a stabilizing effect and also allows sul)- cat’bonyl prodtmcts (18).
sequent reactions, e.g., additions, to take place at many In all the work on tile reactiomis of cat’otenoids with oxi-
parts of the molecule. The cation atid anion t’adicals can dizing amid free-radical reagents, hiowever, tile products
be detected by their charactei’istic spectral properties, that are seen are usually detectable only in much smaller
with intense absorption in the near infrared regiomi (11, amounts than the amount of carotenoid that is destroyed.
12). Also, the substances that cart be isolated are not the pri-
maiy products of the reactions. The primary products will
Chemical reactions: oxidation
be generated extremely rapidly and have only a very
The reactions of carotenoid end groups are important imi shiort lifetime before they undergo further reactions that
classical chemistry, for example, in characterization, dei’i- eventually lead to the formation of stable products that
vatization, and synthesis. Such reactions, however, are can be isolated. Neverthieless, attempts have been made
gemierally not of great significance in relatiomi to function. to imifer what the primary reactiomis may be and to deduce
Here tue most important pam’t of the mnolecule is the the subsequent course of the reactions from the identities
polyene chain. This is a hiighly reactive, electron-rich of these stable products.

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 SERIAL REVIEW

Burton an(l Ingold (19) have proposed thlat whien and course of oxidation reactions. The rates of reaction of
carotene, in solutiomi, reacts with peroxy radicals gener- ,-carotene and its 3,3’-diol, zeaxanthiin, with peroxy
ated via AIBN, a direct addhition takes place to form a radicals generated via azoinitiators, are very similar, but
resonance-stabilized, carbon-centred radical. This could the 4,4’-diol, isozeaxanthin, althioughi it has the same
then react with a further peroxy radical to form a tionradi- chiromophore, reacts more slowly; the 4,4’-diketoties, can-
cal product (20), e.g., thaxanthin and astaxamithiin, react more slowly still. The
differences imi reactivity are attributed to the presence of
R00 +CAR -s ROO-CAR’ the hydroxy or keto substituents in the allylic C-4 and C-
4’ positions, preventing hiydm’ogen abstraction ft’om these
ROO-CAR +ROO -s ROO-CAR-OOR
positiomis to give a resonance-stabilized neutral radical
(21; Woodahl atid Lee et al., utipublished results, 22).
At relatively low oxygen coticentratiotis, this process
would consunle peroxy radicals and the carotenoid wouldh
Carotenoids as antioxidants
act as a chiain-breakimig amitioxidamit. Alternative pathways
are possible,however, especiallyat higher oxygemi con-
Matiy of the most serious human diseases, includimig can-
cemltratiotis when a carotenoid radical could react with
cer and heart disease, at some stage involve oxidation
oxygemi to gemierate a cai’otemioid peroxy radical, CAR-00
processes mediated by free radicals such as HO and
ROO (22).To be an effective antioxidant, a molecule
CAR+O, -sCAR-00 such as a carotenoid would! have to remove these radicals
from the system either by m’eacting with them to yield
harmless products or by disruptimig free-radical chain re-
Thus is an autooxidation process and tile carotetioid actions. It has been shown that carotemioids cati he effec-
eroxy radical could act as a prooxidant, promoting per- tive antioxidants in organic solution under defined
oxidation of unsatui’ated lipid (LH) and hence exacei’bat- conditions, especially at comparatively low oxygen con-
ing damage (18), e.g., centrations (19). Several competing reactions are possi-
ble, however, especially in complex systems. Some of
these may be antioxidant reactions, but others may lead
CAR-00 +LH-*CAR-OOH+L to a prooxidamit action of the carotetioid (18).
L0, -* L-OO’ The situation in vivo is not clear. Thie concentrations of
carotenoids in mammalian tissues generally are much
lower than those used to demonstrate antioxidant behav-
Reactivity of d/j’erent carotenoids. All carotenoids react iot’ in model systems. To act as an antioxidant in vivo, the
rapidly with oxidizing agents atid free radicals, though the carotenoid would need to be imucorporated into the tissues
reactivity depends omi the lemigth of the polyene cht’onio- in the correct location and at a suitable concentration
phuore and, to some extent, on the nature of the end groups. relative to the oxidizing agent and the molecule that is to
The it-electrons of the polyene chain ate delocalized, aI- be protected. It is by no means certain th#{236}at these condi-
though calculations show thiat the electron density is not tions can be fulfilled.
uniform but is greater at or toward the ends of the chromo-
phiore. These are therefore likely to be the preferred sites
for reactions with electrophilic or free-radical species. This PROPERTIES AND MOLECULAR
is seen imireactions with epoxidizing agents that prefereti- INTERACTIONS OF CAROTENOIDS IN VIVO
tially attack the terminal double bond and in the preferred
General considerations
oxidative chain cleavage at the C-7,8 position. Differences
in reactivity can be explained by differences in electronic Much is known about the physical and chemical proper-
density profiles (21; A. A. Woodall, S. W. M. Lee, R. J. ties of carotenoids in simple organic solutions. In vivo,
Weesie, M. J. Jackson, amid C. Britton, unpublished re- however, carotenoids are part of a much niore complex
sults). 4-Carotemie and its 3,3’-diol (zeaxanthin), which system-the living cell-and are in close proximity to
have the same chromophore, have very similar electron other components such as proteimis and lipids, frequently
density profiles. With canthaxanthimu and astaxamithin, how- in organized and ordered structures such as metnbranes.
ever, tueelectron-withdrawing properties of the conjugated The carotenoid must be able to fit into this complex sys-
keto groups at C-4 and C-4’ cause substantial changes in tem in the correct location and orientation.
the electron density along the polyene chain, especially The overall shape, size, and hydrophohicity of a carote-
near to the end groups. Astaxanthin and canthaxamithin muoid are obviously major features that dietermine the abil-
generally react more slowly with oxidizing agents than does ity of a carotenoid to fit into subcellular structures. The
,-carotene, and the preferred sites of reactions such as structural details that characterize the individual carote-
epoxidation are different. noid then define the precise oriemitation that carotenoids
Substituemit groups that do not comitribute to the chro- cart adopt as well as the interactions of the molecule with
mophore can also have a significant influence on the rate its surroundings. Polar fumictional groups provide a focus

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 SERIAL REVIEW

for imuteractions with more polar molecules in ordler to al- penetratimig into tile polar zone and exposed to ami aque-
low the carotenoid to pat’ticipate imuevents in an aqueous ous environment, is also reactive toward free t’adicals
subcellular medium or at an interface or membrane. gemierated imuthe aqueous phase. Some carotetuoids could
Interactions between carotenoid molecules thienuselves thierefore be more effective than others as membrane-
can also hiave a significatit effect on properties. Beimig based protective antioxidamuts.
highly hydrophobic, carotenoids show a strong temidency Differences in tue orientation of thue carotenoid can also
to aggregate and crystallize in aqueous media. The accu- have a substantial effect on the properties of the niem-
mulation of carotenoids as micm’ociystalline aggregates is brane. Thus, carotemuoids such as zeaxanthiti, which have
common imi the chromoplasts of higher plants (e.g., ly- two polar end groups and span the memht’ane, can act as
copene in tomato) (23). Aggregation changes the physical a “rivet” in the menibrane sti’ucture and itict’ease its ri-
properties of carotenoids,-lighit absorptioti and chemical gidity amid mechanical strength (25). The presence of any
reactivity, for example-as well as their effective size amid caroenoid will have some effect on the thickness,
ease of solubilization, thereby affecting their ease of ab- stremigth, and fluidity of that membrane and omuits effec-
sorption and bioavailability in animals amid thieir ability to tiveness as a barrier to watem’ and its permeability to oxy-
enter and functiomi in subcellular structures. geti atid othier molecules (26).It is easy to see that the
effectsof differentcarotenoids may differsuhstatitially.
Molecular interactions
The concentrations of carotenoids in the membt’amies imi
The physical and chemical properties of a cat’otetioid are these studies were, however, mnuch greater thian tiiose
influenced by intetactions with other molecules in its imit- nom’miiahlyfound in biological membranes.
mediate molecular emivit’omumemut,e.g.. lipids and l)mteim.
Carotenoid-protein interactions
Complementary to this, the caroiemioid may imifl&tence th#{236}e
other molecules itu its vicitiity and the strtmcture and jrtj- ltmlerac’tions between cat’otenoids amid pm’oteimusat’e comn-
erties of thie matrix (e.g., membi’ane) itu which it is lo- mon imi all kimuds of living organisms and are of vast
cated. Understanding these imiteractions and theim’ effects physiological importance. The carotemioidls may be greatly
is a major part of understanding how carotenoids fumuction stabilized by the protein. Commonly, carotenoids in vivo
and act in vivo and provides an important and difficult are much more stable than when they are isolated and in
challenge to the carotenoid chemist today. organic solution. Carotetioids associate with hydrophobic
areas in the protein or, especially, with the lipid compo-
Carotenoids in membranes
nents of hi)oproteins. This allows the carotenoid to be
In vivo, carotenoids are commonly located in membt’atues tt’amusported and to function in an aqueous envirotimemil.
where they constitute an integral part of the complex The interactions with the protein can alter the physical or
membrane structure. Features of the localization and ori- chemical properties of the carotenoid. Thus, the bindimig
entation of carotenoids in menibranes cart be studied in of astaxanthin by protein in carotemloprotein complexes
model systems such as phiospholipid liposome bilayers like the blue a-crustacyaniml froni lobster carapace
and monolayers (24). Carotenoids can be incorporated causes a redistribution of electron dlensity in the mole-
into thiesesystems at defined concentrations,but their cule, resulting in a large bathiochromic shift in the light
orientation within the bilayer depends on the structum’e of absorption spectrum from 488 to 632 rim (27).
the individimal carotenoid (21; A. A. Woodall, M. J. Jack- Particularly important itu relation to the functioning of
son, W. Gruszecki, A. Smal, J. Sielewiesiuk, M. C. R. Sy- carotenoids is the role of proteins imumaintaimiing the cot’-
motis, and C. Britton, unpublished i’esults). Thus, the rect positiomi of the carotemuoid with respect to other mole-
hydrocarbons 3j-carotene and lycopemie remaiti emitirely cules. Thus is illustrated pet’f#{232}ctly
by the phiotosynthetic
within tue hydrocarbon inner part of the membramie amid pigmemit-proteimi complexes, in which the pm’otein holds
retain a substantial degree of mobility, albeit with differ- the carotenoid and chlorophylls in close proximity amid in
ent average om’ientations. However, the presence of polar the correct orientation to allow efficient energy tramusfer
substituents in the carotenoid, especially hydroxy groups, (9).
has a profound effect. In the case of the diol zeaxamithin,
for example, polar interactiotis between the hydroxy CONCLUSIONS: FUTURE DEVELOPMENTS
groups on the rings amid the polar head groups of thue Carotenoids are molecules with special properties. Some
phospholipids that constitute the bilayer are major influ- functions of these special molecules are already well es-
ences and hiold the zeaxanthin molecule in a position tablishied, particularly in coloration anti photosymithesis.
spanning the membrane. There is now evidence that carotenoids may also play im-
The positioning of the molecule in the membrane has a portant roles iti human health in addition to theit’ well-
strong bearing omi the reactiotis of the different carote- known provitamin A activity. Carotenoids other thiati
noids with, for example, peroxyradicals (21; Woodall 1343-carotene are provided by the diet amid must also be
and Jacksoti et al., unpublished results). 1343-Carotene considered as possible functionally active molecules, per-
and lycopene are able to react efficiently only with radi- haps with different actions. The current popular view is
cals generated in the hiydrophobic, inner part of the mem- that they can provide some protection agaimist major dis-
brane, whereas zeaxanthin, with its emud groups eases through an antioxidant action (17), although such a

STRUCTURE AND PROPERTIES OF CAROTENOIDS 1557

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 SERIAL
7. Buchecker, R, and Noack, K (1995) Cimcular clichm’oism. imi Carotenoids:
role in vivo must be regarded as not proven. Reported ef- Spectroscopi )Bmitton. C., Liaaen-Jensen, S.. amid Pfamler, H., ecls) Vol. lB.
fects on the immune response system (28) and on cell pp 63-116, Birkhiiiusem, Basel
8. Bm’itton, C. (1995). UVIVisihle spectroscopy. lit Carotenoids: Spectroscopy
gap-junction communication (29) are particularly inter-
(Britton. C., Liammen-Jemisen.S., amid Pfandem’, H., ecls) ‘ol. 1B, sip. 15-62,
esting. Consideration of die properties of carotenoids sug- Bimkhiimmser, Bascl
9. Fmamik,H. A., and Cogciell, R J. (1993) TIme photocliemmitstmy and fumiet ion of
gests that a rohe in membranes may be particularly
marotenoids in photosynthesis. 1mmCarotenoids in Phoiosrnthe.mis )Young, A.,
iniportant; possibilities imiclude simply a protective role amid Brittomi, C. ecls) pp. 252-326, Chapman amid FlaIl. Lomiclon
against membramie damage or a more fundamental struc- 10. Mathews-Roth, M. M. (1982) Medical applications and uses of camomenoicls.
in Carotenoid Cliemistri’ and Biochenmistrr (Britton, C., and Goodwin, T. W.
tural role in strengthening membranes or modifyimig their edls) pp. 297-307. IUPAC-Pc’rgamcmn. Oxford
fluidity and permeability properties. Many factors crucial 11. Simic, MG. (1992) Carotemioid free radicals. Meth. Enzymol. 213,444-453
12. Ltfferty,J.,Truscott, T. C., amidLand, E. J. (1978) Electron transfer reactiomis
to the futictioning of cells or to communication and inter- immvolvingchlorophyllsa and b amidcam’otenoicis.J. C/tern. Soc Faradat’ Trans.
actions betweemi them are located imi or on die membrane, I 74, 2760-2762
13. Ktmm,er, P.. and Jtmcker, E. (1948) Caroonoide, Birkha#{252}ser, Basel [Emiglish
iticluding receptors, transport systems, and membramie- translation (1950) Carotenotds (Braude, E. A., tm.) Eisevmer, Amsmerdamj
boumid or membrane-associated enzymes, some of which 14. Kminsky. N. 1. (1989) Amitioxiclamit fLmnctiomisof cam-otenoicis. Free Rad. Biol.
tIed. 7,617-635
are imivolved in signal transductiomi and various regulatoty 15. Packer,J. E,. Mahood,J. S., Mora-Arellatio, V. O.Slatem,T. F., Willson, R.
processes. The presence or absence of carotenoids in a L., and W,lfenclen, B S. (1981) free radicals and sitiglet oxygemiscavemigers.
Reaction of a pemox radical it uk -camsitemie, diphemi) Ifuran and I ,4-diazo-
membratie could theoretically affect the functioning of bicyclo-2,2.2-oetane. Bloc/tent. Bioplmis. Rn. Commun. 98. 901-906
any of these systems, thereby allowimug the carotenoid to 16. Yamnamoto, Y., liaga, S.. Niki. E.. amid Kumiya. Y. (1984) Oxidation oflipicls.
V. Oxidation of nmethyl linoleute in aqueous dispersion. Bull. C/tern. Soc. Jpn.
influence directly or indirectly an etioi’mous diversity of
57, 1260-1264
processes. Imi addhition, tile old suggestion that, by virtue 17. Palozza, P., amid Krmnsky, N I. (1992) Antioxiclant effects of carotemmoulsimi
of the linear, delocalized it-electron system of the polyene vito and in vitro: au overview. Met/muds Enzt-’nmol.213, 103-420
18 LieI,Ier. D. C. )1993) Atitioxiclamtt reactiomis of camotemtoicls. Ann .1’. ,4cad.
chain, a carotenoici molecule spanilimug a membrane could Sd. 669, 20-31
provide a nieamus of tt’ansferring electrotus across that 19. Burton, C. W., and ingold, K. U., (1984) 13-Camotetie,au unusual I) pm of lipid
amimioxidant. Science 224, 569-573
membrane (28) should not h)e disnuissed. The ability of 20. Krinsky. N I. (1988) Memnl,rane anttm,xtdanms. Ann. VI’. Acrid. SCI. 551,
linear polyenes to act as “moleculat’ wires” in electron 17-33
21. Woodal I, A. A. (1994) Camoien,mids amid the pmiutectmomiof mmiemmmhranes agaimist
tramisfer reawakens imuterest in such possibilities (31). oxidat ire damage. Ph.D. Thesis, tJniversit of Liverpool, t.ivempool
These are excitimig times for tue study of carotenoid 22. ilalliwell. B, mmd Guttericlge, J. 11. C. (1989) Free Radicals i,m Biolog’t and
tledicine, 2rmd Ed. Clarendon, Oxfom’cl
fumictiomis and actions, hut it is essential that such studies 23. Sitte, P., Falk, II., amid Lic’dvogei. B (1980) Clmronimmplasts. in Pignments in
be based oti sound chemical principles and proper comu- P/a,mts, 2nd Ed. )Czygamt, F-C. e(l) pp. 117-1-48 Gustav Fisclirm’, Smutigami
sidet’ation of the t’elatiotuship between structure, proper- 21. Cmuszecki, W. 1., and Sieleiviesiuk, J. I 1990) Orienttmtion of samithoph) Ils in
phosphatulylclioltmie tutmltibilayers. Bloc/mint. Bioplmts.4cta 1023. 105-412
ties, and function. 25. Lazrak, T., Milomi. A., Wolff. C., AIbm’echt, A.-M., MiecIt#{233}. M., Ourissamu, C.,
amid Nakatamui. Y. 11987) Commiparisomuof tIme effects of insemted C t amid C1
tel-inItially clihvclm’oxylatedcarotemiotds ott tImemimechanmeal properties of van-
otis phospholipid resides. hoc/ant. Bmoplmms.Acm 903. 132-ill
REFERENCES 26. Sulxzymtskm. W. K.. Markowska. E.. amid Sielewmesiuk, J. (1991). Effect of
polar c’arotemioids omithe ox gemmaii’dtltffusim,mi-eomwemit mittimimipm’(KI(m(timi I pitl
Stmtmtmh.0. 1987) het to Carotenoids, 2,md Ed IPlander, II.. ccl Birkhiustr. bilayers. Au ESK spimmlabel study. Bloc/tim. hop/mis. 4cm 1068. 68-72
Basm’I 27. Weesme, R. J ., Askin, D., Jamisemm. F. J. II. M., de Cnmsmt.II. J. M., Lugietmlmtmrg,
2. Ku II, I)., and Phmmul,’r, II. (1995) Appemmdix: l.tst of omit mawienoiils. lii J.. amid Bnittmtmu,C. (I t$,15( Pmoteimm-ehmomophom’e mnieraettomts in U-crimstamv-
Ccmroienmmjd.,:Isolation and Ann/isis ) lImit toim, C., Liaaen-Jemmsen, S.. and umiimu, tue mumajor hlmmeeam’ntentmpmom.imm fmsmtmm tlu,’ eamapaee of mlii’ l,,hsti’r,
Plammilem’.II, mc6( Vol IA, pp 295-317. Bim’khltmser, Basel Honmarus g(mnmnmarus.A studs by ‘tC niagic ammglespimtnimtg NIl R. EEl/S Let:.
3. Bm’ittomi. C., Lmaae’mi-Jt’mms,’mi,
S., ammdPfammilem,II., t’ds (1995) Carote,momds: 362.34-38
Iso/nOon a,md ,4naI,sms. I 11, Bmm’kltcmsem’,Busc’I 28. BendicIm. A. 11989) Carotemmoid amid time i immune response. J. S mar. 119.
-I. IUPAC Comnnitsiomi mimiitt, Nomuentlatume ol Om’gammim Cheniitm’y amid IUPAC- 112-115
I U B Commmmmmtssmmmmmon BitmchemmmietmlNommiemitlatume (1975). Nonmenclatmmme of 29. Zlmamug,L.-X.. Comimuey.R. V., amid Bem’tm’ammm, J. S. (1991) Cam’otmmim,ids ,‘nlmamuc,-
(ar(mtem)om(Is(Rob’s approved 1974) Pure .4ppI. Client. 41. 107-431 gap jontmomual cotmimmiumimeation Lmmmdtilt liii I ipmd p,rmi imlatman in C3i’l/ lOT 1/2
3. W,’t’don, B C L, amal Moss, C. 1’. (1995) Stmmmctume amid mmmmmmmemiclat
Lmme.lmm tel Is: r,lat momishmpto themr camicir etiemnoiirevemutmse action. Carcinoge,mesms
Curotenoids: Iso/atom and Anulisrs ) Bm’ittomt.C., Liaaemi-Jensen, S.. ammd 12,2109-2114
Pfumal,r, II., mds) %‘.l. I A, pp. 27-70, Bim’klm3tmser, Bas,’l
30. Plait. J R. (1959) Cam’otemie-dmmnor.acceptor mmmmitmlexe’s
in I)ItotosYflthit’.is.
6. Mo, F. 11995) X-Ray crystallographic stcmdic’s.1mm Carotenoids: Spectroseopi
Sciemice 129, 372-37 I
I Bntton. C., Liunen-Jemisen, S. tmmmd I’fammder, H ..eds ) Vol. 1B, 321-3-42,
Birkhitusem’. Basel 31. Gust, D. (1994) Molecular ivmm’i’samid gmm’ders.Puature (Lomtdomm)372. 133-13-1

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