Organic osmolytes as compatible, metabolic and counteracting cytoprotectants in high osmolarity and other stresses
Biology Department, Whitman College, Walla Walla, WA 99362, USA
e-mail: yancey{at}whitman.edu
Accepted 1 June 2005
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Summary |
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Key words: osmolyte, antioxidant, pressure, urea, trimethylamine oxide, hypotaurine, temperature, compatible solute, counteracting, compensatory
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Introduction: osmolytes in osmoconformers and osmoregulators |
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Osmoconformers are most commonly found in the oceans and include most types
of life other than most vertebrates and some arthropods. The salts (mainly
NaCl) of ocean water yield an average osmotic concentration of 1000
milliosmoles per liter (1000 mOsm), well above the
300400 mOsm
created by the basic solutes found in most cells (K+, metabolites,
proteins, etc.). To prevent osmotic shrinkage, internal fluids of marine
osmoconformers have about the same osmotic pressure as their environment (e.g.
1000 mOsm). However, while extracellular fluids in multicellular organisms are
typically dominated by NaCl, the major osmotic components inside cells (which
raise osmotic pressure above the basal level of 300400 mOsm) are
usually organic osmolytes (Fig.
1). These osmolytes can be up- or downregulated in many species to
prevent osmotic shrinkage or swelling if the osmotic concentration of the
environment changes.
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Osmoregulators, which in the oceans include vertebrates other than hagfish,
coelacanths and elasmobranchs (sharks, skates, etc.), are quite different.
Such animals typically have regulatory organs (e.g. gills, kidneys) that work
to keep internal body fluids at 400 mOsm or less in marine species,
obviating the need for organic osmolytes. This is the pattern inherited by
terrestrial vertebrates, which typically have
300 mOsm body fluids. (The
brine shrimp Artemia in desert salt lakes is another example of a
strong osmoregulator.) However, there are major exceptions to this generalized
pattern, with some osmoregulators utilizing organic osmolytes in certain
situations. For example, in mammals (considered to be exemplary
osmoregulators), cells of the kidney medulla osmoconform to the high osmotic
concentrations in that organ's extracellular fluid. And, as will be discussed
later, osmoregulating fishes in the deep sea have very high levels of an
organic solute that is a major osmolyte in some osmoconformers.
Organic solutes similar or identical to organic osmolytes are also
accumulated by some organisms in thermal and anhydrobiotic stresses, and
possibly under high hydrostatic pressure. These solutes are typically (and
sometimes misleadingly) called `compatible' solutes, based on the concept that
they do not perturb cellular macromolecules even when the solutes are at high
concentrations (Brown and Simpson,
1972). However, as will be discussed, many of these solutes have
cytoprotective properties, such as antioxidation and stabilization of
proteins, that go beyond simple compatibility and that vary from solute to
solute.
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Types of organic osmolytes |
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The basic compatibility hypothesis |
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In concert with the compatibility hypothesis, most osmolytes are neutral
(either zwitterionic or lacking charges) at physiological pH, although some
bacterial and archaeal osmolytes are anionic (e.g. diglycerol phosphate;
Fig. 2) and are paired with
K+ to achieve neutrality
(Martin et al., 1999). In its
simplest form, the compatibility hypothesis also suggests that organic
osmolytes are interchangeable, i.e. that a cell can be osmotically protected
with a variety of compatible osmolytes whether it normally uses them or not.
There is evidence to support this, as illustrated by the following examples.
(1) Growth of Escherichia coli in saline growth media can be improved
with a variety of osmolytes, some not used naturally by the bacterium, added
to the medium (Hanson et al.,
1991
). (2) One cultured line of mammalian kidney medullary cells
(PAP-HT25) in hyperosmotic culture medium uses primarily sorbitol as an
osmolyte. When production of sorbitol is inhibited, cell growth decreases in
parallel with declining cell sorbitol content (inhibition had no effect in
normal medium, in which these cells use little sorbitol;
Yancey et al., 1990a
).
However, addition of glycine betaine (normally absent) to the medium largely
restores viability (Moriyama et al.,
1991
). (3) With normal cells of rat renal medulla, in both primary
cultures (Rohr et al., 1999
)
and in vivo (Yancey et al.,
1990b
), inhibition of sorbitol synthesis triggered a compensating
increase in glycine betaine, such that there were no short-term osmotic
imbalances or apparent damage. These are but a few of many examples.
These experiments suggest that some osmolytes (even from different chemical categories) are functionally interchangeable. Thus, perhaps the reason osmolytes vary among organisms is simply due to different diets or metabolisms that are unrelated to water stress. This may often be the case; for example, the widespread use of (non-nitrogenous) carbohydrate and sulfonium osmolytes in photosynthesizers may arise from nitrogen limitation. However, long-term effects of interchanging osmolytes have not been adequately tested. Also, the compatibility concept does not readily explain why there is such an enormous variety of organic osmolytes, found in all kingdoms of life; Fig. 2 shows only a few examples of the dozens of different known organic osmolytes. Nor does it explain why many organisms employ a complex mixture of osmolytes. As will become apparent, much remains to be learned about the reasons for this variety, but it may result from unique properties of some osmolytes, properties that may be helpful only with certain stresses. These cytoprotective properties fall into two broad categories: (1) protective metabolic reactions and (2) counteraction of destabilizing forces on macromolecules.
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Metabolic protection |
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The metabolic effects of taurine and other osmolytes are summarized in Table 1, and metabolic roles of other osmolytes that are better understood are discussed in more detail below.
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Antioxidation
In some cases, osmolytes may be compatible (i.e. they do not perturb
protein structures), while simultaneously being active cytoprotectants by
serving as antioxidants. For example, it has been found that cyclitols (cyclic
polyols; Fig. 2) and polyols
such as mannitol, which are used by many plants for water retention, may also
scavenge free radicals generated during drought and cold and other stresses;
proline and betaine (also common osmolytes in plants) were not effective
(Orthen et al., 1994;
Shen et al., 1999
). Taurine
has already been mentioned; it cannot scavenge reactive oxygen species (ROS)
but rather seems to enhance other cellular antioxidant functions. However,
taurine can directly bind HOCl (a reactive molecule produced by mammalian
leukocytes) to form N-chlorotaurine
(Schaffer et al., 2003
).
Glycine betaine has also been implicated in reducing lipid peroxidation in
plants (reviewed in Cushman,
2001
). Finally, DMSP (Fig.
2), a major osmolyte of marine algae, also has antioxidant
properties (Sunda et al.,
2002
).
Of all solutes accumulated at relatively high concentrations in some
situations, hypotaurine, with its reactive sulfur atom
(Fig. 2), is one of the
strongest antioxidants, able to scavenge OH radicals (which bond to the sulfur
atom, converting hypotaurine into taurine) as well as HOCl
(Aruoma et al., 1988).
Hypotaurine is known to occur at osmotically significant levels in two
situations: mammalian reproductive fluids (where it appears to act as an
osmolyte and may protect sperm and eggs from oxygen radicals;
Setchell et al., 1993
) and
marine animals living in sulfide-laden waters (see Sulfide detoxification,
below). Why it is not used extensively elsewhere is not clear, but it is
possible that using a strong antioxidant in the absence of radicals could lead
to cell damage in some way. Thus, it may be accumulated primarily for its
antioxidation properties in specific situations, with an osmotic role being a
secondary one.
Redox balance and hypoxia protection
Some osmolytes are not actively protective in themselves, but their
synthesis may be. Glycerol, the archetypical compatible solute
(Brown and Simpson, 1972),
accumulates in certain water-stressed yeasts and algae to high levels (up to
several molar in species in salt ponds and lakes). Glycerol has been shown to
be largely compatible with protein function, but its synthesis also requires
the use of NADH. This may be essential for maintaining cellular redox balance
(by regeneration of NAD+) during anaerobic metabolism; indeed,
mutant yeasts unable to make glycerol are not only highly sensitive to osmotic
stress but also accumulate excessive NADH and thus cannot grow
(Ansell et al., 1997
). Glycerol
may also help reduce radical oxygen production
(Shen et al., 1999
). Proline
accumulation as an osmolyte in water-stressed plants may also be primarily for
maintaining redox states, rather than for (or in addition to) compatibility or
stabilizing properties (reviewed in
Cushman, 2001
).
Other osmolytes may protect cells during hypoxia by other mechanisms.
ß-alanine betaine, a major osmolyte in several species of salt-marsh
plants, appears to replace glycine betaine (found in related plants). Unlike
glycine betaine, ß-alanine betaine requires no direct use of oxygen to
produce it, possibly favoring its use in hypoxic muds of salt marshes
(Hanson et al., 1994).
Recently, high cellular levels of trehalose in fruit flies and transfected
mammalian cells have been found to confer enhanced resistance to hypoxia.
However, this effect has attributed to protein stabilization
(Chen and Haddad, 2004
), the
second cytoprotective category that will be discussed later.
Sulfide/sulfate detoxification
Large concentrations of two taurine derivatives hypotaurine
(Fig. 2) and thiotaurine
have been reported as major organic components of marine invertebrates
living at hydrothermal vents and cold seeps (reviewed in
Pruski et al., 2000a). We have
shown that these solutes are osmolytes in the sense that they create much of
the osmotic pressure of cells, and because they effectively replace the common
osmolytes (e.g. taurine, glycine) of non-vent and non-seep invertebrates
(Fig. 1, clam seep and Riftia
bars; Yin et al., 2000
;
Fiess et al., 2002
). But they
may have another role. Vents and seeps emit high quantities of H2S,
a gas that is toxic to animals but that is a primary energy source for some
microorganisms. Initially, the two taurine derivatives were found in animals
(vestimentiferan tubeworms, vesicomyid clams) that house sulfide-oxidizing
microbial symbionts. Pruski et al.
(2000a
) hypothesized that the
solutes either protect from sulfide radicals and/or store and transport
sulfide (for future use by the symbionts) nontoxically, as follows:
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As evidence for the storage function, hypotaurine is high in all tissues in
these animals, but thiotaurine has been found only in non-trace amounts in
symbiont-bearing tissues: gills in vesicomyid clams and trophosome in
vestimentiferans. This led to a proposal that thiotaurine is a marker of
symbiosis (Pruski et al.,
2000b). Studies in our laboratory suggest the
hypotaurinethiotaurine reaction has a greater, body-wide cytoprotective
role against sulfide in some species: we found that two species of vent
gastropods without endosymbionts have both hypotaurine and thiotaurine as
major osmolytes (Fig. 1, snail
vent bar) and that the ratio of thiotaurine to hypotaurine decreases in
animals held in the laboratory without sulfide
(Rosenberg et al, 2003
).
A different form of sulfur detoxification may be involved in some mangrove
plants (angiosperms). Species of Aegialitis mangroves use
choline-O-sulfate as their primary osmolyte. It has been proposed that the
synthesis of this solute serves to detoxify sulfate, a major anion in seawater
that can be inhibitory at high concentrations
(Hanson et al., 1994). Plants
are more vulnerable than animals to inhibitory ion accumulation since most do
not have excretory tissues. The methylsulfonium osmolyte DMSP
(Fig. 2) may serve a similar
role in marine algae.
Other metabolic roles, and compatibility revisited
Other important metabolic and protective functions have been attributed to
some osmolytes. Other possible functions for taurine have already been
mentioned (see Table 1).
Certainly, carbohydrate osmolytes such as glucose, sorbitol and trehalose
(commonly accumulated with temperature stress such as freezing) can serve as
immediate sources of energy after an organism emerges from a stress-induced
dormancy. Defense against predators is another possible function of some
osmolytes. DMSP (Fig. 2),
widespread in marine microalgae, can be broken down into a gas, DMS
(dimethylsulfide), and acrylate, which may serve to repel grazers such as
copepods (Wolfe, 2000;
Van Alstyne and Houser, 2003
).
In some terrestrial plants, hydroxyprolinebetaine is accumulated in water
stress; an isomer of this
(trans-4-hydroxy-L-prolinebetaine) is a strong inhibitor
of animal acetylcholine esterase and therefore may deter herbivores
(Hanson and Burnet, 1994
).
The active metabolic roles of osmolytes that have been presented here indicate that many compatible solutes are not interchangeable, which has significant implications for practical applications (more will be said on this later). However, the basic compatibility concept is still probably correct in the sense that most or all of these compounds should not bind to and perturb most macromolecules.
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Stabilization and counteraction |
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Perturbing solutes: urea and salts
Some organic osmolytes are able to offset, or `counteract', effects of
solutes that also build up in osmotic stress and that perturb macromolecules.
Urea is such a perturbant. It is a highly concentrated waste produce in
mammalian kidneys and urine, and it is the major organic osmolyte in marine
elasmobranch fishes (ureosmotic animals)
(Fig. 1, shark and mammal renal
bars). At concentrations in these fishes and mammalian kidneys (e.g. several
hundred millimolar), urea destabilizes many macromolecular structures and
inhibits functions such as ligand binding. However, these animals have other
osmolytes, mainly methylamines such as TMAO and GPC (Figs
1,
2). These solutes do not
exhibit simple compatibility, but rather show strong enhancement of protein
activity and stability at physiological concentrations. For TMAO, this
property is additive with urea's effects such that they counteract, most
effectively at about a 2:1 urea:TMAO ratio
(Fig. 3A), which is similar to
physiological levels (roughly 400:200 mmol l1 in
shallow-water elasmobranch fishes; Fig.
1, shark bar). Counteraction of urea has been extensively
confirmed in a variety of protein systems (reviewed by
Yancey, 2001) and has also
been recently demonstrated for nucleic acids in the form of bacterial tRNA
(Fig. 3B;
Gluick and Yadav, 2003
). TMAO
is usually a better stabilizer than other osmolytes, including glycine betaine
and glycerol (Ortiz-Costa et al.,
2002
; Russo et al.,
2002
; Yancey et al.,
2004
; Kumar et al.,
2005
), perhaps explaining why TMAO is preferred in ureosmotic
fishes. Like basic compatibility, counteraction occurs whether a protein is
from a urea-accumulating tissue or not (e.g. bacterial tRNA noted above).
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Methylamines can also offset some perturbing effects of salts. Methylated
derivatives of glycine (sarcosine, dimethylglycine and glycine betaine) can
counteract NaCl inhibition of a plant enzyme's activity, with protection
increasing with degree of methylation
(Pollard and Wyn Jones, 1979).
Many other studies show counteraction of salt inhibition by methylamines,
including complex cellular systems (reviewed by
Yancey, 2001
).
Anhydrobiosis
Disaccharides, most notably trehalose, commonly build up in anhydrobiotic
dormant organisms (e.g. baker's yeast, resurrection plants, tardigrades).
However, these sugars do not exhibit non-interactive compatibility and are not
osmolytes since the organisms lose most of their water. Rather, these solutes
appear to bind to macromolecules and membranes, in essence replacing water
molecules and maintaining the basic structure of these large biomolecules.
Moreover, trehalose forms a glass-like state (i.e. it vitrifies) in the dry
state, which also helps preserve cellular structures. Trehalose appears to be
better than other biological sugars in forming a protective vitrified state
(Crowe et al., 1998).
Trehalose also is a non-reducing sugar, which, unlike glucose and some other
monosaccharides, does not engage in `browning' (Maillard) reactions that can
damage proteins during drying (reviewed by
Tunnacliffe and Lapinski,
2003
).
Although in vitro experiments have clearly established the
efficacy of trehalose, recent studies are questioning its role in
anhydrobiosis in nature. In particular, bdelloid rotifers have been found to
undergo reversible anhydrobiosis without accumulating trehalose or similar
solute (Tunnacliffe and Lapinski,
2003). The issue raised by these observations remains
unresolved.
Freezing
Freezing is another stress faced by many ectotherms in which specific small
solutes play a role. Strategies to survive body temperatures below freezing
fall into two categories: freeze avoidance and freeze tolerance. Avoiders
(whose body fluids do not freeze) use a variety of mechanisms such as
non-colligative antifreeze proteins, reduced nucleation sites and
supercooling. Many avoiders also accumulate (in all body fluids) high levels
of colligative antifreezes, or cryoprotectants, which are typically compatible
carbohydrates such as glycerol. Well-studied model animals that use glycerol
include gall moth (Epiblema scudderiana) caterpillars
(Storey and Storey, 1996) and
rainbow smelt, which, unlike most teleost fish, is nearly an osmoconformer due
to the accumulation of glycerol as an antifreeze
(Raymond, 1992
).
Freeze tolerators, by contrast, let their extracellular fluids freeze with
the aid of ice nucleators; however, intracellular fluids typically do not
freeze due to the presence of, once again, colligative cryoprotectants such as
glycerol, trehalose and sorbitol. In this situation, cells shrink somewhat due
to increasing extracellular concentrations caused by ice formation. However,
shrinkage is limited by the compatible solutes serving as osmolytes as well as
antifreezes. Model animals include gall fly (Eurosta solidaginis)
larvae and intertidal barnacles, which use glycerol, wood frogs (Rana
sylvatica), which use glucose, and New Zealand alpine wetas
(Hemideina maori), which use trehalose
(Baust and Lee, 1982;
Storey and Storey, 1996
;
Neufeld and Leader, 1998
).
Carbohydrates are also found as cryoprotectants in many plants.
Thus, small carbohydrates have been selected as colligative antifreezes
independently in different taxa and strategies. In addition, certain amino
acids such as proline also accumulate in some freeze-tolerant animals
(Storey and Storey, 1996;
Neufeld and Leader, 1998
), but
not to levels that would suggest an antifreeze function. In fact, there is
some evidence that cryoprotectants fall into two categories with distinct
roles. First, the carbohydrates such as glycerol act as both colligative
antifreezes, and, in freeze tolerance, as osmolytes (i.e. they reduce loss of
cellular water), while at the same time being compatible with macromolecules.
Non-carbohydrate solutes might be substituted for this role, but carbohydrates
may be preferred as the easiest to both synthesize and transport across
membranes rapidly. They also form a ready energy source for use upon emergence
from freezing.
By contrast, a second group of cryoprotectants may have stabilizing
functions that other solutes do not. In particular, proline and trehalose
appear to bind to head groups of membrane phospholipids, in effect replacing
water molecules. Thus, they can stabilize membranes during cell shrinkage
(Rudolph and Crowe, 1985;
Storey and Storey, 1996
).
High temperature
Almost all natural osmolytes and other compatible solutes can increase
protein thermal stability in vitro; although for most osmolytes, this
occurs only at non-physiologically high concentrations. However, certain
carbohydrate solutes may be used in living organisms to counteract temperature
disruption of proteins. For example, heat stress induces accumulation of
trehalose in yeast, in which the disaccharide can protect enzymes from thermal
denaturation (Singer and Lindquist,
1998).
Hyperthermophilic archaea from marine hydrothermal vents accumulate
ß-mannosylglycerate, di-myo-inositol phosphate and K+
at high temperatures and salinities. One species has high levels of diglycerol
phosphate at high temperatures (Fig.
2; Martin et al.,
1999). Both trehalose and anionic osmolytes such as these sugar
phosphates (paired with K+) can stabilize proteins at high
temperatures (even boiling in some cases), while other osmolytes are much less
effective. One study showed this type of counteraction to be effective on
proteins of archaea, yeast and mammals, suggesting a universal ability
(Santos and da Costa,
2002
).
Hydrostatic pressure in the deep sea
The most recent example of counteraction has been found in the deep sea,
where high hydrostatic pressure destabilizes protein structure and ligand
binding. Although some proteins appear to have evolved pressure resistance,
many have not or have done so incompletely
(Siebenaller and Somero,
1989). Our recent studies suggest that some osmolytes can help
with pressure. In shallow marine animals, TMAO
(Fig. 2) is either absent or
found at less than 100 mmol kg1 wet mass (except in
ureosmotic fish such as sharks). However, deep-sea teleost fishes
(osmoregulators usually thought to have low organic osmolyte levels), as well
as certain crustaceans, skates and other osmoconforming animals, have up to
300 mmol kg1 TMAO, increasing with depth
(Fig. 4A). Initially, we found
the increase in TMAO down to 3 km depth
(Gillett et al., 1997
;
Kelly and Yancey, 1999
);
recently, we have found that the pattern extends linearly down to 4.8 km both
among different species and within the same species
(Fig. 4A;
Yancey et al., 2004
). In
osmoconformers, high levels of TMAO essentially replace the common osmolytes
of shallow relatives, e.g. glycine in shrimp, urea in skates, which, in a
species from 3 km depth, had a 1:2 urea:TMAO ratio rather than the typical 2:1
ratio of shallow elasmobranchs (Rajids,
Fig. 4A). A similar pattern has
been confirmed for some sharks (Treberg
and Driedzic, 2002
).
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Since hydrostatic pressure is the only environmental factor that is linear
with depth, we hypothesized that TMAO might counteract pressure effects.
Indeed, TMAO (but not other common osmolytes) in vitro was able to
offset pressure inhibition of (1) stability of several homologues of lactate
dehydrogenase, (2) polymerisation of actin, (3) enzyme-substrate binding for
two enzymes and (4) growth of living yeast cells
(Yancey and Siebenaller, 1999;
Yancey et al., 2002
,
2004
). One example is shown in
Fig. 4B. Other hypotheses to
explain the high TMAO in deep-sea animals, such as diet, buoyancy, energy
savings (Kelly and Yancey,
1999
) and byproduct of lipid storage
(Seibel and Walsh, 2002
), do
not readily explain the highly linear pattern. Thus, TMAO may not be serving
primarily as an osmolyte but rather as a pressure counteractant.
Other researchers have found that some sugars and polyols can counteract pressure destabilization of bacterial enzymes (Saad-Nehme, 2001), a concern for the food industry, which is increasingly using pressure for sterilization. These findings raise the possibility that other osmolytes might help counteract pressure in nature.
We have recently found that some deep-sea animals (echinoderms, some
mollusks, polychaetes, vestimentiferans, etc.) do not have TMAO, probably
because their taxa lack the biosynthesis pathways. However, all have high
levels of potentially stabilizing (and often unusual) osmolytes, including the
polyol scyllo-inositol, and other methylamines, including glycine
betaine, GPC and several unsolved methylamines
(Fig. 1, 2.9 km bars)
(Fiess et al., 2002;
Yancey et al., 2002
). Also,
vesicomyid clams from 26.4 km depth contain an unsolved
serine-phosphate-ethanolamine compound that increases linearly with depth,
forming over 60% of the osmolyte pool of the deepest species
(Fig. 1, clam 4 km and 6 km
bars; Fiess et al., 2002
).
Since organic phosphates (e.g. diglycerol phosphate, GPC) have been found to
be stabilizers of proteins in other situations, perhaps this compound is also
a stabilizer.
Deep-sea bacteria have been found to accumulate the osmolyte
ß-hydroxybutyrate in correlation with exposure to hydrostatic pressure as
well as to osmotic pressure (Martin et
al., 2002). The investigators proposed the term `piezolyte' for
solutes that are accumulated at high pressure. (This suggests that parallel
terms such as `thermolyte', `cryolyte' and `anhydrolyte' might be considered!)
Whether the serine-phosphate or ß-hydroxybutyrate can offset the effects
of pressure is unknown. However, a recent study on marine bacteria has shown
that adaptation to salinity synergistically enhances survival at high
pressure, suggesting that some osmolytes may protect against both stresses in
these microorganisms (Kaye and Baross,
2004
).
Mechanisms of stabilization
The compatible and counteracting hypotheses predict that
solutemacromolecule effects are universal, i.e. stabilization should
occur with proteins or membranes from any organism regardless of whether it
uses osmolytes or not (Wyn Jones et al.,
1977; Yancey et al.,
1982
). How can these effects be universal, given the great
diversity in macromolecular structures? The mechanisms are not fully known,
but universal watersolutemacromolecule interactions are involved
for many osmolytes and related solutes. Destabilizers such as some salt ions
and urea generally bind to proteins, causing them to unfold because this
exposes more groups that undergo thermodynamically favorable binding with the
destabilizer (Fig. 5C). By
contrast, many stabilizing solutes do not bind to proteins; indeed, they are
excluded from a protein's hydration layer (the water molecules adjacent to a
protein's surface) (Timasheff,
1992
). Recently termed the `osmophobic' effect by Bolen and
Baskakov (2001
), exclusion
arises from an apparent repulsion between stabilizers and the peptide
backbone, explaining how this effect can be universal. Because of this
repulsion, proteins will tend to fold up more compactly, since this will
reduce exposure of the peptide-bond backbone to thermodynamically unfavorable
interactions with the stabilizing solute
(Fig. 5A,B).
|
Other stabilizers may work through more direct interactions, as discussed
earlier for membrane interactions of trehalose and other solutes used in
anhydrobiosis and freezing. Taurine has also been reported to bind to
membranes through ionic interactions
(Schaffer et al., 2003). The
charged osmolytes of hyperthermophiles (mannosylglycerate, diglycerol
phosphate; Fig. 2) appear to
enhance native protein conformations through electrostatic interactions, in
addition to preferential exclusion (Faria
et al., 2004
).
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The `yin and yang' of cytoprotection |
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Practical applications of osmolytes |
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Unanswered questions and conclusions |
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In conclusion, a variety of other stresses (oxidative, protein-perturbing,
etc.) can co-occur with water stress, and many osmolytes probably have unique
properties that protect cells from these disturbances, either through
cytoprotective metabolic reactions such as antioxidation or stabilization of
macromolecules through watersolute or solutemacromolecule
interactions. Understanding these properties will help greatly in elucidating
both basic biochemical adaptations and the practical use thereof and may be
particularly important if some protective properties of osmolytes are harmful
in the absence of a perturbant to offset. If this view is correct, the term
`compatible solute' is often inappropriate. Instead, osmolytes and related
solutes should be called `compatible' only when they clearly have no effect on
macromolecules and should be called `counteracting' when they are used in
nature to offset a perturbant. Or, perhaps, the more recent term `compensatory
solute' (Gilles, 1997) should
be adopted.
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