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Coenzyme Q is well defined as a crucial component of the oxidative phosphorylation process in mitochondria which converts the energy in carbohydrates and fatty acids into ATP to drive cellular machinery and synthesis. New roles for coenzyme Q in other cellular functions are only becoming recognized. The new aspects have developed from the recognition that coenzyme Q can undergo oxidation/reduction reactions in other cell membranes such as lysosomes. Golgi or plasma membranes. In mitochondria and lysosomes, coenzyme Q undergoes reduction/oxidation cycles during which it transfers protons across the membrane to form a proton gradient. The presence of high concentrations of quinol in all membranes provides a basis for antioxidant action either by direct reaction with radicals or by regeneration of tocopherol and ascorbate. Evidence for a function in redox control of cell signaling and gene expression is developing from studies on coenzyme Q stimulation of cell growth, inhibition of apoptosis, control of thiol groups, formation of hydrogen peroxide and control of membrane channels. Deficiency of coenzyme Q has been described based on failure of biosynthesis caused by gene mutation, inhibition of biosynthesis by HMG coA reductase inhibitors (statins) or for unknown reasons in ageing and cancer. Correction of deficiency requires supplementation with higher levels of coenzyme Q than are available in the diet.
Plasma membrane redox functions. Two types of transplasma membrane electron transfer are known. One type uses coenzyme Q as a transmembrane electron carrier [72]; the other uses a low redox potential cytochrome b558 complex. This enzyme is analogous to the peroxide generating GP91 phox of neutrophils (n [40, 41]) and may be characteristic of transformed cells (t [73]). In addition, cytosolic ascorbate can reduce external semidehydroascorbate through a cytochrome b561 in some cells. Three different NAD(P)H dehydrogenases (reductases ) on the plasma membrane can reduce coenzyme Q [17, 18]. Two different enzymes are indicated for oxidation of the Q quinol. One is a coenzyme Q oxidase at the outer surface which can oxidize quinol at the outer surface with production of superoxide [37]. The other is an external site sensitive to iron chelators [39]. It can be expected that autooxidation of the iron in neutral pH will produce superoxide [74]. It is not known which system is responsible for diferric transferrin reduction at the cell surface [75]. The recycling of the iron on the tranferrin through reoxidation by oxygen could also produce superoxide since diferric transferrin stimulates NADH oxidation by plasma membrane. The peroxide produced by either of these oxidase systems can then feed back into the cell to activate gene transcription [27], SH-S-S controlled calcium channels [28, 76] or inhibit phosphotyrosine phosphatase [77]. The mechanism of control of the Na/H antiport is not known. Tf is transferrin. The mechanism for redox control of the Na/H antiport [12] or Ca activated K channels is not known [78]. Gene transcription regulated by the hemopexin system is controlled by surface copper reduction dependent on coenzyme Q [79,80].
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Review
Biochemical Functions of Coenzyme Q
10
Frederick L. Crane, PhD
Department of Biological Sciences, Purdue University, West Lafayette, Indiana
Key words: energy coupling, antioxidant, transmembrane signaling, gene expression
Coenzyme Q is well defined as a crucial component of the oxidative phosphorylation process in mitochon-
dria which converts the energy in carbohydrates and fatty acids into ATP to drive cellular machinery and
synthesis. New roles for coenzyme Q in other cellular functions are only becoming recognized. The new aspects
have developed from the recognition that coenzyme Q can undergo oxidation/reduction reactions in other cell
membranes such as lysosomes, Golgi or plasma membranes. In mitochondria and lysosomes, coenzyme Q
undergoes reduction/oxidation cycles during which it transfers protons across the membrane to form a proton
gradient. The presence of high concentrations of quinol in all membranes provides a basis for antioxidant action
either by direct reaction with radicals or by regeneration of tocopherol and ascorbate. Evidence for a function
in redox control of cell signaling and gene expression is developing from studies on coenzyme Q stimulation of
cell growth, inhibition of apoptosis, control of thiol groups, formation of hydrogen peroxide and control of
membrane channels. Deficiency of coenzyme Q has been described based on failure of biosynthesis caused by
gene mutation, inhibition of biosynthesis by HMG coA reductase inhibitors (statins) or for unknown reasons in
ageing and cancer. Correction of deficiency requires supplementation with higher levels of coenzyme Q than are
available in the diet.
Key teaching points:
Coenzyme Q is needed for energy conversion.
Coenzyme Q is an essential antioxidant.
Coenzyme Q regenerates other antioxidants.
Coenzyme Q stimulates cell growth and inhibits cell death.
Decreased biosynthesis may cause deficiency.
INTRODUCTION
The point to emphasize is that coenzyme Q has several
biochemical functions [1]. The well recognized functions are in
mitochondrial energy coupling and its action as a primary
regenerating antioxidant. Less well established functions in-
clude oxidant action in the generation of signals and control of
cellular redox state. By participation in transmembrane electron
transport coenzyme Q can carry reducing equivalents to the
inside of vesicles or to the outside of cells. There is also
evidence for a role in proton gradient formation in endomem-
branes and at the plasma membrane. In addition, there is
evidence that coenzyme Q can take part in control of membrane
structure and phospholipid status [2,3].
Coenzyme Q is 2,3-dimethoxy,5-methyl, 6-polyisoprene
parabenzoquinone. The coenzyme Q
10
found in humans has a
polyisoprene chain containing 10 isoprene units (5 carbons
each) or a total of 50 carbons. The all trans polyisosoprene
ensures an affinity for the interior of cell membranes. The two
methoxy groups contribute to the specificity in enzyme action
as may the methyl group. The fully substituted quinone ring
does not allow addition reactions with thiol groups in the cell
such as glutathione, thioredoxin or thioctic acid. The functional
group is the quinone ring. By reduction of the quinone to quinol
a carrier of protons and electrons is produced [4].
Coenzyme Q is distributed in all membranes throughout the
cell [5]. In mitochondria there are well defined protein binding
sites on the enzymes involved in coenzyme Q oxidation reduction
Presented in part at the 41st Annual Meeting, American College of Nutrition, Las Vegas, Nevada, October 12, 2000.
Address correspondence to: Frederick L. Crane, Ph D, Department of Biological Sciences, Purdue University, West Lafayette, Indiana.
Journal of the American College of Nutrition, Vol. 20, No. 6, 591–598 (2001)
Published by the American College of Nutrition
591
[6]. Enzymes in other membranes can be expected to have
specific coenzyme Q binding sites, but these have not been
defined. In addition there is coenzyme Q floating in the phos-
pholipid bilayer of the membranes. The free form may float
with the all trans polyisoprene chain extended in a long linear
structure with the methyl groups intercalated in the fatty acid
chains of the lipid. There is also evidence that in some cases the
polyisoprenoid chain may be folded into a shorter, thicker
structure. It is thought that the isoprenoid chain may help to
stabilize the lipid bilayer [2]. The quinone head group can be
either the oxidized (quinone) or reduced (quinol) form. In most
membranes enzymes have been defined which can reduce the
quinone and oxidize the quinol. The percent in quinol form in
various membranes and serum ranges from 30% to 90%, de-
pending on the metabolic state of the cell [7]. The quinol
(hydroquinone) is more hydrophilic, so the head group can lie
closer to the surface of the membrane. The change of position
with oxidation/reduction may modify structural or enzymatic
properties in the membrane. For example, the redox state may
control activity of phospholipases in the membrane [3].
Genetic mutation, ageing, cancer and statin type drugs can
cause a decrease of coenzyme Q in serum or tissue (Table 1).
The precise membranes in all cells which have less are not
known, but deficiency can be observed in mitochondria of
some cells but not in others. The amount of coenzyme Q in the
diet is not sufficient to increase serum coenzyme Q signifi-
cantly. Significant increase of coenzyme Q in serum requires
supplementation with about 100 mg/day.
ENERGY COUPLING
Coenzyme Q is an essential part of the cellular machinery
used to produce ATP which provides the energy for muscle
contraction and other vital cellular functions. The major part of
ATP production occurs in the inner membrane of mitochondria,
where coenzyme Q is found. The coenzyme Q has a unique
function since it transfers electrons from the primary substrates
to the oxidase system at the same time that it transfers protons
to the outside of the mitochondrial membrane. This transfer
results in a proton gradient across the membrane. As the pro-
tons return to the interior through the enzymatic machinery for
making ATP, they drive the formation of ATP. The coenzyme
Q is bound to the oriented enzymatic protein complexes. It is
oxidized and releases protons to the outside and picks up
electrons and protons on the inside of the mitochondrial mem-
brane [8, 9].
There are two protein complexes in the membrane where
electrons and protons are transferred through coenzyme Q. The
first is the primary reductase where coenzyme Q is reduced by
NADH (complex I). During the reduction process four protons
are transported across the membrane for every coenzyme Q
reduced [8 (Fig. 1)]. The details of this process are still unclear,
but it has been proposed that coenzyme Q is reduced and
reoxidized in the complex twice before electrons are transferred
to a second loosely bound coenzyme Q to form quinol which
can travel through the lipid in the membrane to a second
complex where the quinol is oxidized again (complex III) with
transfer of protons across the membrane [9 (Fig. 2)]. The
details of quinol binding and oxidation at the binding site in this
complex are well known. As in complex I, there is a cyclic
oxidation-reduction-reoxidation with the oxidation and proton
release step always on the outside so that protons are released
in the right direction. Again the oxidation-reduction cycle al-
lows for four protons to cross the membrane for each quinol
oxidation cycle. The quinone cycle thus doubles the efficiency
of the coenzyme Q in building up the proton charge across the
membrane which allows twice as much ATP production than a
simple one step oxidation of quinol. After the cycle is com-
pleted the oxidized quinone migrates through the membrane to
be rereduced at complex I.
A simpler form of energy conversion based on coenzyme Q
reduction-oxidation is found in lysosomes [10]. In this case the
Table 1. Coenzyme Q Deficiency in Humans
Basis Tissue Analysis
% Decrease
from Control
Ref
Genetic Lymphocytes [49]
Age*** Myocardium 72% [50]
Age* Heart 58% [63]
Age* Pancreas 83% [63]
Age* Adrenal 50% [63]
Age* Liver 17% [63]
Age* Kidney 45% [63]
Age** Skin epidermis 75% [21]
Genetic Skin fibroblasts 90% [49]
Pravastatin
0
Serum 20% [64]
Lovastain
0
Serum 29% [64]
Simvastatin
0
Serum 26% [65]
Cancer (pancreas) Serum 30% [66]
Diabetic (NIDDM) Serum 65% [67]
* Change from age 1921 to age 7781.
** Change from age 30 to age 80.
*** Change from avg. age 58 1.7 to 76 6.8.
0
HMG CoA reductase inhibitors of isoprene synthesis.
Fig. 1. Reductive Q cycle. Scheme proposed [8] for reduction and
proton transfer through the tightly bound coenzyme Q in complex I.
Partial oxidation of quinol allows recycling of the quinone to carry
more protons across the membrane than electrons transferred to the
losely bound coenzyme Q which travels in the lipid bilayer to be
oxidized in complex III.
Biochemical Functions of Coenzyme Q
10
592 VOL. 20, NO. 6
quinol transfers a proton across the lysosomal membrane to
acidify the inside which involves energy input to work against
a proton gradient. No ATP can be formed since the lysosomal
membrane does not have a proton driven ATP synthetase. The
acidification of the lysosome activates hydrolytic enzymes for
digestion of cellular debris. In other words, coenzyme Q ener-
gizes cell house cleaning. The details of the enzymes and
possible Q binding sites in the lysosomal membrane are not
known. The enzyme complex in the membrane involves reduc-
tion of coenzyme Q by NADH in the cytoplasm and reoxida-
tion of the quinol by oxygen.
Another site where coenzyme Q may be involved in vesicle
acidification is in pinocytotic endosomes which engulf iron and
transferrin bound to transferrin receptors and carry it into the
cell. There is a redox system in the membranes of these vesicles
which can acidify their interior [11]. Reduction of transferrin-
bound iron in an acid environment releases the iron for uptake
into the cytoplasm. The possible role of coenzyme Q in iron
reduction and proton transfer in these membranes has not been
established.
Another role for coenzyme Q in proton movement is indi-
cated at the plasma membrane. In this situation coenzyme Q is
involved in activation of Na/H exchange across the mem-
brane carried out by the Na/H antiport. The energy for this
process is based on a high concentration of Na outside the
cell which exchanges for protons in the cell. The Na is then
pumped out of the cell by the Na/K ATPase which obtains
energy from ATP. During this ATP action excess Na is
released so the cell develops an inside negative membrane
potential which is important for many cellular functions and
transport action [12]. Coenzyme Q is involved in a plasma
membrane electron transport system by which NADH in the
cytoplasm transfers electrons through coenzyme Q to electron
acceptors such as iron or oxygen outside the cell. When this
system is activated, the proton release through the H/Na
antiport is greatly increased. When the system is inhibited by
inhibitory coenzyme Q analogs, the antiport is inhibited. As a
result of activation of the antiport, the interior of the cell
becomes more alkaline. The mechanism by which the coen-
zyme Q dependent electron transport activates the antiport is
not known [13].
If the Na/H antiport is inhibited by amiloride, the trans-
plasma membrane electron transport is accompanied by a slow
release of protons equivalent to two protons released per quinol
oxidized. This proton release indicates that the reduction oxi-
dation of the coenzyme Q in the membrane is organized as in
the lysosomes. In contrast, the proton release by activation of
the antiport is more that ten times greater than the electron
transport driven proton transfer.
ANTIOXIDANT FUNCTIONS
Coenzyme Q is well located in membranes in close prox-
imity to the unsaturated lipid chains to act as a primary scav-
enger of free radicals. The amount of CoQ in many membranes
is from three to 30 times the tocopherol content [14] (also see
Table 2)]. Since much of the coenzyme Q in cell membranes is
in the quinol form [15], it can be a very effective antioxidant
[16]. Even more important is the presence of enzymes in all
membranes which can reduce any coenzyme Q quinone radical
generated by reaction with lipid or oxygen radicals. At least
three enzymes are known which can keep the coenzyme Q
reduced in plasma and endomembranes [1]. These enzymes are
(1) NADH cytochrome b5 reductase [17], (2) NADH/NADPH
oxidoreductase (DT diaphorase [17]), (3) NADPH coenzyme Q
reductase [18]. In mitochondria the NADH and succinate de-
hydrogenases can keep coenzyme Q partly reduced. Reductases
1 and 3 in endomembranes can be especially important by one
electron transfer to rereduce any semiquinone generated by
reaction of quinol with a radical. The DT diaphorase is unique
since it can directly reduce, by 2 electron transfer, any quinone
formed without intermediate formation of the semiquinone.
Under conditions of oxidative stress induced by nutritional lack
of selenium and
-tocopherol, the coenzyme Q in membranes
is greatly increased. The amount of DT diaphorase attached to
Fig. 2. Oxidative Q cycle. Scheme proposed [9] for partial oxidation of
the quinol to provide electrons from the semiquinone for rereduction of
quinone to quinol with uptake of protons for transfer across the mem-
brane.
Table 2. Coenzyme Q in Cell Membranes and Relation to
-Tocopherol
Rat Liver Membranes
CoQ/
toc
mol/mol
CoQ
g/mg protein
Mitochondria (cristae) 35 1.9
Plasma membrane 21 0.7
Peroxisomes 3 0.3
Lysosomes 3 1.9
Golgi membranes 1 2.6
Endoplasmic reticulum 1 0.2
Data based on [5,14].
Biochemical Functions of Coenzyme Q
10
JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION 593
membranes where it can reduce coenzyme Q is also remarkably
increased [19]. Similar decrease in
-tocopherol induced by
peroxisomal proliferator is accompanied by a large increase in
coenzyme Q [14].
A direct demonstration of the effectiveness of coenzyme Q
as an antioxidant can be shown with coenzyme Q deficient
yeast. A yeast mutant deficient in coenzyme Q synthesis shows
more lipid peroxide formation than normal yeast [20]. Another
direct demonstration of elimination of free radicals is shown by
coenzyme Q treatment of skin in older persons. Luminescence
from free radicals is eliminated when a skin cream containing
coenzyme Q is applied [21].
In addition to direct antioxidant radical scavenging, the
quinol can rescue tocopheryl radicals produced by reaction
with lipid or oxygen radicals by direct reduction back to to-
copherol [22]. Without coenzyme Q in a membrane, regener-
ation of tocopherol is very slow. The regeneration of tocopherol
can also be observed in low density lipoprotein where a small
amount of coenzyme Q protects a larger amount of tocopherol.
This function is presumably favored by the high percent of
quinol present in blood [23, 24].
There is some evidence that the coenzyme Q dependent
electron transport across the plasma membrane can be used to
regenerate ascorbate outside the cell from ascorbate radical
(monodehydroascorbate [25]). Ascorbate inside the cell can be
regenerated by a glutathione based system. Regeneration out-
side requires electron transfer through the plasma membrane,
some of which depends on the presence of coenzyme Q in the
membrane.
CELL SIGNALING AND
GENE EXPRESSION
Coenzyme Q can participate in several aspects of oxidation/
reduction control of signal origin and transmission in cells. The
autooxidation of the semiquinone formed in various mem-
branes during electron transport activity can be a primary basis
for generation of H
2
O
2
[1,26]. The H
2
O
2
in turn activates
transcription factors such as NF
K
B to induce gene expression
[27]. Peroxide can also be involved in calcium signaling in
cardiac muscle [28]. It is also possible that reactive oxygen
species generation may lead to suppression of other genes. The
quinone can also participate in oxidation of thiol groups on
growth factor receptors or membrane ion channels. An example
is ryanodine receptor controlled Ca⫹⫹ release which may also
be related to oxygen sensing [29,30]. On the other hand, re-
duction of disulfide bonds by the quinol would require energy
driven reverse electron transport since the redox potential of
coenzyme Q is higher (100 mV) than the thiol-disulfide
couple (320 mV). A proton gradient driven electron transport
as seen in reduction of NAD by succinate in mitochondria
would drive this disulfide reduction by the quinol. Control of
the redox state of protein disulfide isomerase at the cell surface
by the quinol oxidase or the quinone reductase has been dis-
cussed [31].
Formation of the coenzyme Q semiquinone in complex III
of mitochondria has long been cited as a primary source of
superoxide and subsequently hydrogen peroxide in cells [32].
This source is controlled by the redox state or degree of energy
coupling in the mitochondria [26]. Similar control applies to
H
2
O
2
production at the succinate dehydrogenase (complex II)
or NADH dehydrogenase (complex I) sites for reduction/oxi-
dation of coenzyme Q [26 (Fig. 3)]. It is expected that binding
of the semiquinone in these complexes would decrease autooxi-
dation, but any condition which disturbs the equilibrium be-
tween quinone and binding protein to allow quinone exposure
may encourage peroxide production [33].
Since coenzyme Q is not restricted to mitochondria and the
coenzyme Q in other membranes undergoes oxidoreduction
[10,34,35], there is probably potential for peroxide generation
in all membranes. Certainly lysosome, Golgi and plasma mem-
branes are candidates. Plasma membranes do generate peroxide
during oxidation of NADH [36].
Although there are enzymes which can reduce coenzyme Q
in all endomembranes and in plasma membrane, the presence
of binding sites which can protect the semiquinone from au-
tooxidation and prevent subsequent peroxide production are
unknown. Furthermore, enzymes for oxidation of quinol in
plasma membrane have been identified. A cell surface NADH
oxidase and a transplasma membrane NADH oxidase have
been observed [37]. The surface oxidase also acts as a coen-
zyme Q quinol oxidase [38] and shows evidence for superoxide
generation [37]. The quinol oxidase portion of the transmem-
brane oxidase has not been isolated but it appears to require
non-heme iron since it is reversibly inhibited by impermeable
iron chelators [39]. The transmembrane NADH oxidase re-
quires coenzyme Q [35]. A second transplasma membrane
NAD(P)H oxidase has been defined which is homologous with
Fig. 3. Sites for semiquinone formation in the redox complexes of
mitochondria. Complex I, II and III generate semiquinone which takes
part in normal electron transfer. If semiquinone accumulates because of
inhibitors, excess substrate or excess proton accumulation, the semiqui-
none can be autooxidized to produce superoxide [26]. Semiquinone
formation in fatty acid oxidation (FA) would probably be associated
with the electron transfer flavoprotein (ETFP) coenzyme Q oxi-
doreductase ETFQR [70]. Glycerol-3-phosphate dehydrogenase also
reacts with coenzyme Q (not shown [71]).
Biochemical Functions of Coenzyme Q
10
594 VOL. 20, NO. 6
the superoxide generating NADPH oxidase found in neutrophil
plasma membrane [40, 41]. This oxidase uses cytochrome b558
to produce superoxide and is characteristic of transformed and
tumor cells. The coenzyme Q dependent transmembrane en-
zyme has been defined in rat liver and heart cells and appears
to be a normal component in all animal cells [13]. The extent
to which it can be activated to produce superoxide has not been
defined. Possible evidence that superoxide production induced
by phorbol myristate acetate depends on coenzyme Q is sug-
gested by retinoic acid inhibition in Balb 3T3 cells [42]. Reti-
noic acid does not inhibit transformed Balb 3T3 cells. Loss of
retinoic acid response suggests that the b558 oxidase predominates
over the coenzyme Q system in some transformed cells [1].
At this point we do not know which plasma membrane
electron transport system is responsible for superoxide and
peroxide formation at the cell surface of different types of cells
(Fig. 4). The inhibition of transplasma membrane electron
transport in transformed cells by antitumor drugs but not in
untransformed cells suggests that the b
558
(Mox 1) enzyme is
activated in these cells as it is in the ras mutant cells [1,43,44].
On the other hand retinoic acid appears to be a specific inhib-
itor for the system in nontransformed cells which presumably is
the coenzyme Q dependent system [44] since the transmem-
brane enzyme in normal liver cells is largely dependent on
coenzyme Q [35].
The effect of the plasma membrane electron transport on
cell proliferation is probably not exclusively related to gener-
ation of H
2
O
2
. This is seen in the effect of ferricyanide as an
external electron acceptor on the expression of c-myc and c-fos
genes in C3H 10T1/2 cells [45]. Since ferricyanide will destroy
any peroxide produced at the cell surface, its growth effect may
be based on alteration of the cytosolic redox state by oxidation
of NADH [46]. The basis for inhibition of apoptosis by coen-
zyme Q remains to be established. The effect may be based on
redox control or on membrane structure control and modifica-
tion of phospholipid as in the inhibition of ceramide formation
[17, 47]. The role of coenzyme Q in signal transduction, gene
expression and membrane channels is therefore a new area in
need of further study. There is ample evidence that it is in-
volved in significant control functions.
DEFICIENCY
In normal healthy individuals coenzyme Q is synthesized in
all cells from tyrosine (or phenylalanine) and mevalonate [48].
Only four cases are reported with genetic based failure of
synthesis [49]. Low levels of coenzyme Q are found in disease
or ageing [21,50,51,52]. It is not clear how the distribution of
coenzyme Q in tissue is controlled. In tissues with unimpaired
synthetic capacity, it appears that coenzyme Q in each mem-
brane reaches a saturation level [53]. Thus supplementation
with coenzyme Q does not increase tissue levels above normal
(except in liver and spleen). This is especially true in young,
healthy animals. In older animals with decreased coenzyme Q,
in some tissue, supplemental coenzyme Q can restore normal
levels [50,53,54]. In addition to decrease in biosynthesis, other
factors may affect levels or function of coenzyme Q. These
include increase in degradation [55] or changes in membrane
lipids to impede quinone movement [56]. Changes of coen-
zyme Q in different tissues and cell membranes with ageing
seem to vary. For example, ageing rats decrease coenzyme Q
Fig. 4. Plasma membrane redox functions. Two types of transplasma
membrane electron transfer are known. One type uses coenzyme Q as
a transmembrane electron carrier [72]; the other uses a low redox
potential cytochrome b558 complex. This enzyme is analogous to the
peroxide generating GP91 phox of neutrophils (n [40, 41]) and may be
characteristic of transformed cells (t [73]). In addition, cytosolic ascor-
bate can reduce external semidehydroascorbate through a cytochrome
b561 in some cells. Three different NAD(P)H dehydrogenases (reduc-
tases) on the plasma membrane can reduce coenzyme Q [17, 18]. Two
different enzymes are indicated for oxidation of the Q quinol. One is a
coenzyme Q oxidase at the outer surface which can oxidize quinol at
the outer surface with production of superoxide [37]. The other is an
external site sensitive to iron chelators [39]. It can be expected that
autooxidation of the iron in neutral pH will produce superoxide [74]. It
is not known which system is responsible for diferric transferrin re-
duction at the cell surface [75]. The recycling of the iron on the
tranferrin through reoxidation by oxygen could also produce superox-
ide since diferric transferrin stimulates NADH oxidation by plasma
membrane. The peroxide produced by either of these oxidase systems
can then feed back into the cell to activate gene transcription [27],
SH-S-S controlled calcium channels [28, 76] or inhibit phosphotyrosine
phosphatase [77]. The mechanism of control of the Na/H antiport
is not known. Tf is transferrin. The mechanism for redox control of the
Na/H antiport [12] or Ca⫹⫹ activated K channels is not known
[78]. Gene transcription regulated by the hemopexin system is con-
trolled by surface copper reduction dependent on coenzyme Q [79,80].
Biochemical Functions of Coenzyme Q
10
JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION 595
selectively in skeletal muscle mitochondria [57] but increase
coenzyme Q in mitochondria from brain [58]. Changes in other
membranes with ageing need to be determined in relation to
loss of function or antioxidant capability.
Nutritional replenishment of coenzyme Q requires a higher
level than is available in most food (Table 3). The normal level
in blood is around 1
g/mL [51,59,60]. To increase the con-
centration significantly requires at least 100 mg/day which can
increase the level in blood to around 2
g/mL or more. An
increase to 2
g/mL in blood can be therapeutic for various
conditions [61]; this may indicate that a high blood level is
needed to get coenzyme Q into deficient tissues. Even with
large amounts of heart or herring in the diet, it would be
difficult to supply 100 mg/day.
CONCLUSION
The important point to consider is that coenzyme Q is not
just an agent for energy transduction in mitochondria. It is a
functional element in all cell membranes. Part of this wider
function is based on its antioxidant action with unique capacity
for regeneration of redox capacity and a unique location deep in
membrane structure. In addition there is growing evidence for
a role in control of cell functions and growth. Gene activation
or suppression may be based on peroxide production or control
of thiol redox state. Other signal functions may involve control
of membrane channels, structure and lipid stability.
Biosynthesis in mitochondria and endoplasmic reticulum
provides sufficient coenzyme Q for normal individuals. It is not
clear if two separate sites of synthesis are involved and how
they are controlled [5,62]. Evidence for deficiency is based on
genetic failure, age, disease or drugs which inhibit synthesis.
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Table 3. Coenzyme Q in the Diet
Food
CoQ
10
Content
g/g
Daily
Portion
g/day
CoQ
10
Intake
mg/day
Meat Pork heart 203 120 24
Chicken leg 17 120 2.0
Beef heart 41 120 4.8
Beef liver 19 120 2.3
Lamb leg 2.9 120 3.5
Frog leg 5 120 0.6
Fish Herring 27 26 0.7
Trout 11 100 1.1
Vegetable Cauliflower 0.6 200 0.12
Spinach 2.3 200 0.46
Potato .24 200 0.05
Fruit Orange 2.2 200 0.44
Data based on [68,69].
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598 VOL. 20, NO. 6

Supplementary resource (1)

... It is also known as coenzyme Q10 because its chemical structure is that of a 1,4-benzoquinone, where Q refers to the quinone group while the number 10 refers to the number of isoprenoid sub-units. It is ubiquitously distributed in practically all cells, being the reason why it`s called ubi-quinone, which gives fuel to the mitochondria for a sufficient function [1]. ...
... The main function of CoQ10 in the body is the production of cellular energy or adenosine triphosphate (ATP). It is the most critical component in all mitochondria (Figure 1) which are present in practically every cell in our body totaling from 600-2000 mitochondria per cell [1]. The mitochondria are in fact fuel organelles where the biological energy called ATP (adenosine triphosphate) is produced. ...
... In addition, CoQ10 is also a potent antioxidant and it helps protect tissues and cellular components in the body from oxygen radicals (ROS). In addition, CoQ10 has been shown to preserve the myocardial sodium-potassium ATPase activity while stabilizing myocardial calcium-dependent channels while other important functions of CoQ10 such as cell signalling and gene expression have also been described [1,2]. ...
... Coenzyme Q10 is a lipophilic benzoquinone compound that can be both synthesised endogenously and taken from outside. It is present in all cells (37). It functions as a coenzyme in the oxidation systems of the body. ...
... Coenzyme Q10 in cell membranes is localized close to unsaturated fat chains. Because of this position, it is the first compound that fights free radicals (37). As the first protector of the defence system against free radicals formed as a result of oxidative stress, it destroys them. ...
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Plasma membrane electron transport systems are involved in different cellular functions, including the regulation of growth and development. Two components are essential to understand these systems in plasma membrane: the electron donors and acceptors. It is widely accepted that pyridine nucleotides are the electron donors for the different redox systems described up to now. NADH is specific for the universal animal and plant cell plasma membrane electron transport, which reduces a wide range of oxidants including oxygen, iron compounds and free radicals (Rubinstein and Luster, 1993; Lüthje et al., 1997; Asard et al., 1998; Bérczi et al., 1998). NADPH is, however, specific for the plant turbo system, equivalent to the ferric reductase complex in yeast (Dancis et al., 1992; Askwith and Kaplan, 1998) and for the respiratory burst oxidase in macrophages (Segal, 1987; Segal et al., 1998).
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Nuclear factor kappa B (NF-kappa B) is a transcription factor crucially involved in glial and neuronal function. NF-kappa B is ubiquitously distributed within the nervous system, and its inducible activity can be discerned from constitutive activity. Prototypic inducible NF-kappa B in the nervous system is composed of the DNA-binding subunits p50 and p65 complexed with an inhibitory I kappa B-alpha molecule. A number of signals from the cell surface can lead to rapid activation of NK-kappa B, thus releasing the inhibition by I kappa B. This activates translocation of NF-kappa B to the nucleus, where it binds to kappa B motifs of target genes and activates transcription. Previous findings have identified reactive oxygen intermediates (ROI) as a common denominator of NF-kappa B activating signals. More specifically, hydrogen peroxide (H(2)O(2)) might be used as second messenger in the NF-kappa B system, despite its cytotoxicity. Analysis of pathways leading to NF-kappa B activation in the nervous system has identified a number of ROI-dependent pathways such as cytokine-and neurotrophin-mediated activation, glutamatergic signal transduction, and various diseases with crucial ROI involvement (e.g., Alzheimer's disease, Parkinson's disease, experimental autoimmune encephalomyelitis, multiple sclerosis, amyotrophic lateral sclerosis, and injury). A number of NF-kappa B-specific target genes contribute to the production of ROl or are involved in detoxification of ROIs. In this review, possible mechanisms and regulatory pathways of ROI-mediated NF-kappa B activation are discussed. Antiox. Redox Signal. 1, 129-144, 1999.
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Coenzyme Q10 or ubiquinone has been shown to have both anti-cancer and immune system enhancing properties when tested in animals. Preliminary results reported here suggest that it might inhibit tumour-associated cytokines. Clinical studies conducted with combination therapies of CoQ10 and other antioxidants are ongoing, but the results are difficult evaluate owing to the lack of proper control groups and of initial randomisation. Also on the basis of some anti-cancer effects of antioxidants reported in literature, further animal studies and a proper clinical trial of coenzyme Q10 in cancer patients are needed.
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The endogenous biosynthesis of the quinone nucleus of coenzyme Q10 (CoQ10) from tyrosine is dependent on adequate vitamin B6 nutriture. Lowered blood and tissue levels of CoQ10 have been observed in a number of clinical conditions. Many of these clinical conditions are most prevalent among the elderly. Kalen et al. have shown that blood levels of CoQ10 decline with age. Similarly, Kant et al. have shown that indicators of vitamin B6 status also decline with age. Blood samples were collected from 29 patients who were not currently being supplemented with either CoQ10 or vitamin B6. Mean CoQ10 concentrations was 1.1 ± 0.3 μg/ml of blood. Mean specific activities of EGOT was 0.30 ± 0.13 μmol pyruvate/hr/108 erythrocytes and the mean percent saturation of EGOT with PLP was 78.2 ± 13.9%. Means for all parameters were within normal ranges. Strong positive correlation was found between CoQ10 and the specific activity of EGOT (r =0.5787, p
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The inferior recovery of cardiac function after interventional cardiac procedures in elderly patients compared to younger patients suggests that the aged myocardium is more sensitive to stress. We report two studies that demonstrate an age-related deficit in myocardial performance after aerobic and ischemic stress and the capacity of CoQ10 treatment to correct age-specific diminished recovery of function. In Study 1 the functional recovery of young (4 mo) and senescent (35 mo) isolated working rat hearts after aerobic stress produced by rapid electrical pacing was examined. After pacing, the senescent hearts, compared to young, showed reduced recovery of pre-stress work performance. CoQ10 pretreatment (daily intraperitoneal injections of 4 mg/kg CoQ10 for 6 weeks) in senescent hearts improved their recovery to match that of young hearts. Study 2 tested whether the capacity of human atrial trabeculae (obtained during surgery) to recover contractile function, following ischemic stress in vitro (60 min), is decreased with age and whether this decrease can be reversed by CoQ10. Trabeculae from older individuals (> or = 70 yr) showed reduced recovery of developed force after simulated ischemia compared to younger counterparts (< 70 yr). Notably, this age-associated effect was prevented in trabeculae pretreated in vitro (30 min at 24 degrees C) with CoQ10 (400 MicroM). We measured significantly lower CoQ10 content in trabeculae from > or = 70 yr patients. In vitro pretreatment raised trabecular CoQ10 content to similar levels in all groups. We conclude that, compared to younger counterparts, the senescent myocardium of rats and humans has a reduced capacity to tolerate ischemic or aerobic stress and recover pre-stress contractile performance, however, this reduction is attenuated by CoQ10 pretreatment.