Coenzyme Q10 and its Effective Sources

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.


Introduction
Coenzyme Q10 (2,3 dimethoxy, 5-methyl, 6decaprenyl 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).  (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).  (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). 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). 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.