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Coenzyme Q10 (2,3-dimethoxy, 5-methyl, 6-decaprenyl benzoquinone, CoQ10) is naturally present in many organisms. It has key roles in several biochemical pathways. CoQ10, as an electron and proton carrier for energy coupling leads to Adenosine Triphosphate (ATP) formation. Furthermore, in medicine, the pharmacological use of CoQ10 has attracted more attention due to its benefits in treating cardiovascular and degenerative neurologic diseases. CoQ10 can be produced by chemical synthesis, extraction from biological tissues and microbial fermentation. It is found in plants such as soya bean, peanut, palm oil and litchi pericarp and in animals such as pelagic fish, beef and pork hearts. Various analytical methods have been published for the extraction and analysis of CoQ10 from different matrices. Biological production of CoQ10 offers an environmentally benign option based on the enzymatic catalysis at the cellular level. Moreover, this process due to ease of control and low production costs offers more advantages over the existing technologies. © 2016 Hamideh Vaghari, Roholah Vaghari, Hoda Jafarizadeh-Malmiri and Aydin Berenjian.
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© 2016 Hamideh Vag hari, Roholah Vagha ri, Hoda Jafarizadeh-Mal miri and A ydin Berenjia n. This open access article is
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American Journal of Biochemistry and Biotechnology
Review
Coenzyme Q10 and its Effective Sources
1Hamideh Vaghari, 2Roholah Vaghari, 1Hoda Jafarizadeh-Malmiri and 3Aydin Berenjian
1Faculty of Chemical Engineering, Sahand University of Technology, Tabriz, Iran
2Faculty of Nuclear Engineering, Shahid Beheshti University, Tehran, Iran
3Faculty of Science and Engineering, School of Engineering, University of Waikato, Hamilton 3240, New Zealand
Article history
Received: 08-06-2016
Revised: 06-10-2016
Accepted: 07-10-2016
Corresponding Author:
Hamideh Vaghari
Faculty of Chemical
Engineering, Sahand University
of Technology, Tabriz, Iran
Email: vaghari_h@yahoo.com
Abstract: Coenzyme Q10 (2,3-dimethoxy, 5-methyl, 6-decaprenyl
benzoquinone, CoQ10) is naturally present in many organisms. It has key
roles in several biochemical pathways. CoQ10, as an electron and proton
carrier for energy coupling leads to Adenosine Triphosphate (ATP)
formation. Furthermore, in medicine, the pharmacological use of CoQ10
has attracted more attention due to its benefits in treating cardiovascular
and degenerative neurologic diseases. CoQ10 can be produced by chemical
synthesis, extraction from biological tissues and microbial fermentation. It
is found in plants such as soya bean, peanut, palm oil and litchi pericarp
and in animals such as pelagic fish, beef and pork hearts. Various analytical
methods have been published for the extraction and analysis of CoQ10
from different matrices. Biological production of CoQ10 offers an
environmentally benign option based on the enzymatic catalysis at the
cellular level. Moreover, this process due to ease of control and low
production costs offers more advantages over the existing technologies.
Keywords: CoQ10, Adenosine Triphosphate (ATP), Mitochondrial
Enzymes, Extraction, Microbial Fermentation
Introduction
Coenzyme Q10 (2,3 dimethoxy, 5-methyl, 6-
decaprenyl benzoquinone, CoQ10) is present in many
organisms (Fig. 1) (Xue et al., 2012). CoQ10 also known
as ubiquinone or ubiquinone-10 and its active form is
ubiquinol, is abundant in plants, animals and
microorganisms (Yuan et al., 2012). It plays a crucial
role in the transfer of electrons between respiratory
complexes of the electron transport chain, located within
the inner mitochondrial membrane (Cluis et al., 2012).
Recently CoQ10 found a wide range of therapeutic
applications (Tokdar et al., 2014; Langsjoen, 1994).
Fig. 1. Chemical structure of CoQ10 (Jankowski et al., 2016)
Extensive research has been conducted to increase
CoQ10 production to meet growing demands for this
product. CoQ10, can be produced by three methods:
Chemical synthesis, extraction from biological tissues
(animal and plant) and microbial fermentation
(Laplante et al., 2009). Microbial biosynthesis offers
several advantages over chemical synthesis and extraction
including specificity towards the all-trans biologically
active isomer of CoQ10 and the reduced production of
environmentally hazardous waste based on the enzymatic
catalysis at the cellular level for CoQ10 production (Cluis,
2012). Moreover, microbial fermentation found to be an
attractive method for industrial production of CoQ10
(Lee et al., 2004; Park et al., 2005).
The present study aimed to discuss about importance,
benefits of CoQ10 and also its effective sources and
extraction methods.
Importance and Benefits of CoQ10
Application of CoQ10 in foods and animal tissue has
attracted special attention owing to its crucial roles in
many biochemical pathways (Rodriguez-Estrada et al.,
2006). CoQ10 is the coenzyme for at least three
mitochondrial enzymes (complexes I, II and III).
Hamideh Vag hari et al. / American Jo urnal of Bioche mistry and Bi otechnology 2016, 12 (4) : 214.219
DOI: 10.3844/ajbbsp.2016.214.219
215
Fig. 2. Central role of CoQ10 in electron transport chain
Fig. 3. CoQ10 decline with age (Littarru and Lambrechts, 2011)
CoQ10 as shown in Fig. 2 is a core component of
cellular energy production. Due to its involvement in ATP
synthesis, CoQ10 affects the function of every cell in the
body, making it important for the health of all tissues and
organs (de Dieu Ndikubwimana and Lee, 2014).
CoQ10 has been shown to have quite powerful
antioxidant potential. Therefore, it can effectively defend
against reactive oxygen species and free radical damage,
protects the body from damage caused by harmful
molecules (Ruiz-Jiménez et al., 2007) through protecting
membranes and proteins from oxidation (Cluis, 2012).
There is evidence that CoQ10 is playing a part in
transcriptional regulation of genes, some of which play
roles in inflammatory responses and in cholesterol
metabolism (Schmelzer et al., 2007). Furthermore, in the
medicine filed CoQ10 has received increasing attention due
to its benefits in treating cardiovascular and degenerative
neurologic diseases (Weant and Smith, 2005).
CoQ10 is naturally produced in the body, but its
levels decrease as we age and may be low in people with
cancer, genetic disorders, diabetes, heart problems and
Parkinson’s disease (Fig. 3). Symptoms of CoQ10
deficiency include heart failure, high blood pressure and
chest pain. On the other hand, the concentration of CoQ10
in the body decreases year by year, indicating that it has a
close relationship with aging (Fig. 2). For these reasons,
some people rely on CoQ10 supplements. The daily intake
of CoQ10 is suggested as 12 mg kg−1 (Rujiralai et al.,
2014). More recently, nutraceutical supplements
containing CoQ10 have gained a significant popularity in
health management sections (Buettner et al., 2007).
Table 1. Overview of CoQ10 contents in various foods
(Pravst et al., 2010)
Animal organ CoQ10 concentration [mg/kg]
Beef
Heart 113
Liver 39–50
Muscle 26–40
Pork
Heart 11.8–128.2
Liver 22.7–54.0
Muscle 13.8–45.0
Chicken
Heart 116.2–132.2
Fish
Sardine 5–64
Mackerel
Red flesh 43–67
White flesh 11–16
Salmon 4–8
Tuna 5
Table 2. Overview of CoQ10 contents in various plants
(Pravst et al., 2010)
Plant CoQ10 concentration [mg/kg]
Oils
Soybean 54–280
Olive 4–160
Grapeseed 64–73
Sunflower 4–15
Pistachio nuts 20
Hazelnuts 17
Almond 5–14
Nuts
Peanuts 27
Walnuts 19
Sesame seeds 18–23
Pistachio nuts 20
Hazelnuts 17
Almond 5–14
Vegetables
Parsley 8–26
Broccoli 6–9
Cauliflower 2–7
Spinach up to 10
Grape 6–7
Chinese cabbage 2–5
Fruit
Avocado 10
Blackcurrant 3
Strawberry 1
Orange 1–2
Grapefruit 1
Apple 1
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CoQ10 supplements have shown positive effects on
patients suffering from conjunctive heart failure and
acute myocardial infarction (Hodgson et al., 2002;
Yang et al., 2010). It has been proved that CoQ10 helps
treat, muscular dystrophy and periodontal disease
(Yang et al., 2010; Mancini and Balercia, 2011).
CoQ10 Effective Sources
CoQ10, can be produced by chemical synthesis,
extraction from biological tissues (plants and animal)
and microbial fermentation (Laplante et al., 2009). In
the wake of environmental awareness, the chemical
options became least desirable due to inherent uses of
solvents and chemicals in the process (Tokdar et al.,
2014).
Plant and Animal Sources of CoQ10
CoQ10 is naturally present in small amounts in a
wide variety of foods, but is particularly high in animal
meat organs such as heart, liver and kidney, beef as well
as soy oil, sardines, mackerel and peanuts (Langsjoen,
1994). The highest content is found in meat and fish
tissues and viscera due to their high levels of
mitochondria (Reig et al., 2015). Moreover, presence of
CoQ10 in bee pollen was investigated (Xue et al., 2012).
The results of CoQ10 contents in animal organs and
various plants are overviewed in Table 1 and 2.
Microbial Sources of CoQ10
As summarized in Table 3, CoQ10 can be produced
by microbial fermentation including fungi (e.g.,
Candida, Sporidobolus, Rhodotorula, Neurospora,
Aspergillus) and bacteria (e.g., Agrobacterium,
Paracoccus, Cryptococcusi, Rhodobacter, Tricosporon).
Moreover, presence of CoQ10 in Artemia samples as a
Crustacean was investigated (Rujiralai et al., 2014).
Microbial production offers an environmentally
benign option based on the enzymatic catalysis at the
cellular level for CoQ10 assembly. Moreover, this
approach is attractive to the industry because the
process is easy to control at a relatively low
production cost (Tokdar et al., 2014).
Table 3. CoQ10 production in wild types, chemical mutants and recombinant strains
Source Specific CoQ10 content (mg/g DCW) Reference
Wild type
Agrobacterium tumefaciens ATTC 4452 1.9 Jeya et al. (2010)
Agrobacterium tumefaciens KY-8593 1.2 Cluis et al. (2007)
Paracoccus denitrificans ATCC 19367 0.86 Choi et al. (2005)
Protaminobacter ruber 1.52 Jeya et al. (2010)
Pseudomonas N84 1.2 Jeya et al. (2010)
Rhizobium radiobacter ATCC 4452 5.3 Choi et al. (2005)
Rhizobium radiobacter A603-35-gapA 5.27 Koo et al. (2010)
Rhizobium radiobacter KCCM 10413 11.84 Ha et al. (2009)
Rhizobium radiobacter T6102 1.95 Seo and Kim (2010)
Rhizobium radiobacter WSH 2601 1.91 Wu et al. (2003)
Rhodobacter sphaeroides BCRC 13100 8 Yen and Chiu (2007)
Rhodobacter sphaeroides BCRC 13100 4.5 Yen et al. (2010)
Rhodobacter sphaeroides FERM-P4675 2.7 Choi et al. (2005)
Sporidiobolus johnsonii 10.5 Dixson et al. (2011)
Recombinant strain
Escherichia coli 0.29 Choi et al. (2005)
Escherichia coli 1.41 Choi et al. (2009)
Escherichia coli 2.428 Zahiri et al. (2006)
Escherichia coli 0.44 Huang et al. (2011)
Escherichia coli 0.45 Huang et al. (2011)
Escherichia coli 3.24 Huang et al. (2011)
Escherichia coli 0.51 Zhang et al. (2007)
Escherichia coli 0.19 Zhang et al. (2007)
Escherichia coli 0.77 Zhang et al. (2007)
Rhizobium radiobacter 5.27 Koo et al. (2010)
Rhizobium radiobacter 8.3 Lee et al. (2007)
Chemical mutants
Agrobacterium tumefaciens AU-55 9.6 Choi et al. (2005)
Agrobacterium sp. 1.96 Jeya et al. (2010)
Agrobacterium tumefaciens
KCCM 10413 8.54 Cluis et al. (2007)
Agrobacterium tumefaciens KCCM 10413 9.71 Jeya et al. (2010)
Rhodobacter sphaeroides 8.7 Jeya et al. (2010)
Rhodobacter sphaeroides Co-22-11 car 2.6 Cluis et al. (2007)
Rhodobacter sphaeroides Co-22-11 2.5 Choi et al. (2005)
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However, due to the limits of CoQ10 accumulation in
cells, strain improvements have been made using genetic
engineering (using recombinant nucleic acid
technology), chemical mutagenesis and high hydrostatic
pressure treatment (Kim et al., 2015).
Industrial production of CoQ10 have predominantly
relied on bacterial and yeast mutants due to their higher
CoQ10 content (Tokdar et al., 2014). The isolation of
strains by mutagenesis and selection on inhibitors has
shown to be the most successful strategy to enhance
CoQ10 yields (Yen and Shih, 2009). Table 2 summarizes
CoQ10 production by some wild, chemical mutants and
recombinant strains.
CoQ10 Effective Extraction Methods
Liquid–liquid extraction or ultrasound extraction by
using a mixture of hexane and 2-propanol found to be
the most common methods for extraction of CoQ10 from
different samples (Xue et al., 2012). For example,
CoQ10 from fresh tobacco leaves and litchi pericarp was
extracted using ultrasonic extraction in the presence of
ethanol and hexane (Rujiralai et al., 2014).
The two extraction methods generate a large amount
of toxic chemicals within the process, which causes a
significant environmental and health impact. Therefore,
it is clearly preferable to obtain extracts by eliminating
the use of toxic solvents (Xue et al., 2012).
Accelerated Solvent Extraction (ASE) was first
developed by Dionex Corporation, in 1996 and then
validated on a commercially-available, automated
extraction system ASE a new extraction procedure for
sample preparation, combines elevated temperatures and
pressures with liquid solvents. Through this method
organic solvents are used at high pressures and
temperatures above the boiling point. In recent years, the
popularity of ASE has increased since it can provide a
higher extraction efficiency with low solvent volumes
and a short extraction time in comparison with some
classical extraction technologies such as liquid–liquid
extraction and soxhlet extraction. ASE with ethanol and
an acid- thermal treatment with a petroleum ether
extractant were documented for extracting CoQ10 from
bee-collected pollen and Agrobacterium tumefaciens,
respectively (Richter et al., 1996).
Conclusion Remarks
CoQ10, a lipid-soluble endogenous pro-vitamin
found naturally in the mitochondria, is present in
many organisms. It has crucial roles in many
biochemical pathways and important health functions.
Levels of CoQ10 decrease as we age and may be low
in people with cancer, genetic disorders, diabetes,
heart problems and Parkinson’s disease. For these
reasons, some people rely on CoQ10 supplements.
CoQ10 can be produced from some microorganisms,
plants and animals. It is important to establish a
suitable extraction and analysis method for
determining the content of CoQ10 in different
foodstuffs. The most common methods for extracting
CoQ10 from different samples are liquid–liquid
extraction or ultrasound extraction. In recent years,
the popularity of ASE has increased since it can
provide higher extraction efficiency with low solvent
volumes and a short extraction time in comparison
with some classical extraction technologies. Microbial
production offers an environmentally benign option
and is attractive to the industry because of easy to
control at a relatively low production cost. However the
better precursors which could be combined for more
CoQ10 production needs future studies. New methods
for development of CoQ10 production in a better
microorganism, which could produce high CoQ10
yield, could also be evaluated in the future. Finally, a
type of reactor that provides high cell concentrations,
high productivity and easy separation of the products
could be determined from further research.
Funding Information
The authors have no support or funding to report.
Author’s Contributions
All authors equally contributed in this work.
Ethics
This article is original and contains unpublished
material. The corresponding author confirms that all of
the other authors have read and approved the manuscript
and no ethical issues involved.
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... Coenzyme Q10 (CoQ10) is one of the natural compounds often employed as an antioxidant, which plays a key role in stabilizing plasma and other intracellular membranes that protect against membrane phospholipid peroxidation 7 . CoQ10 acts by maintaining skin quality against free radicals 3 which have been known to activate the mitogen-activated protein kinase (MAPK) pathway that produces matrix metalloproteinases (MMPs) such as collagenase, thus damaging collagen fibers [8][9][10] . During ageing, the levels of CoQ10 in organs, including the skin, also decrease with the result that it is necessary to supply CoQ10 to achieve normal levels of between 0.50 and 1.65 μg/mL within the body. ...
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Coenzyme Q10 (CoQ10) is a naturally produced organic molecule which acts as an antioxidant agent, including in skin anti-ageing, and plays a major role in the social determinants of health. However, its level in the body will decrease during ageing. Therefore, an external supplement is required to repair damaged skin, especially the skin dermis layer. This study aims to evaluate the use of a protransfersomal emulgel to improve the skin delivery and stability of CoQ10 which demonstrates low water solubility, poor permeability and instability. CoQ10 was initially dissolved in oleic acid at a weight ratio of 1:56. Protransfersome was then loaded with CoQ10 (Protransf-CoQ10) and prepared using a composition of L-α-Phosphatidylcholine and Tween 80 at a molar ratio of 85:15. The Protransf-CoQ10 was dispersed in an emulgel base consisting of Tween 80 and Span 80 to produce Protransf-CoQ10 emulgel. The in vivo studies of anti-aging activity and irritability were further evaluated by applying daily 200 mg of emulgels twice a day to a 4 cm ² section on the back of a UV-ray aging-induced male Balb/c mouse 20 min before irradiation. The results showed that Protransf-CoQ10 could transform into transfersomal vesicles with particle sizes of approximately 201.5 ± 6.1 nm and a zeta potential of − 11.26 ± 5.14 mV. The dispersion of Protransf-CoQ10 into emulgel base resulted in stable Protransf-CoQ10 Emulgel during 28 days of observation at low temperatures. Moreover, the in vivo study revealed that Protransf-CoQ10 Emulgel successfully increases the collagen density and number of fibroblast cells in UV radiation skin-aged induced-mice which reflects its potential for repairing the skin ageing process. In addition, the 24-h topical application of Protransf-CoQ10 Emulgel showed that no erythema or skin rash was observed during the study. In conclusion, loading CoQ10 into protransfersomal Emulgel successfully enhanced the stability and anti-ageing efficacy enabling its potential use as anti-ageing cosmetics.
... Both chemical synthesis and extraction from biological tissues involve the use of organic solvents and chemicals, leading to the pro-duction of waste, which nowadays is trying to be avoided due to environmental concerns. In addition, neither of these two techniques exhibit specificity toward the all-trans biologically viable isomer of CoQ10, which adds costs due to the extra purification steps needed (Vaghari, Vaghari, Jafarizadeh-Malmiri, & Berenjian, 2016). For these reasons, and because the process is inexpensive and easy to control, CoQ10 is mainly produced by microbial biosynthesis, including fungi, bacteria, and yeast. ...
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The cell growth and CoQ10 (coenzyme Q10) formation of Rhizobium radiobacter WSH2601 were investigated in a 7-1 bioreactor under different dissolved oxygen (DO) concentrations. A maximal CoQ10 content (C/B) of 1.91 mg/g dry cell weight (DCW) and CoQ10 concentration of 32.1 mg/l were obtained at the appropriate DO concentration of 40% (of air saturation). High DO concentration was favourable to the cell growth of Rhizobium radiobacter WSH2601. In order to achieve the maximal yield of CoQ10 production, a new DO-stat feeding strategy was proposed, which significantly improved cell growth and CoQ10 formation. With this strategy, the maximal CoQ10 concentration and DCW reached 51.1 mg/l and 23.9 g/l, respectively, which were 67 and 44.8% higher than those obtained in the batch culture with DO concentration controlled.