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Rhodoquinone (RQ) is a modified
In the case of the prokaryotic organism ''R. rubrum'', RQ has been shown to be synthesized by addition of an amino group to a pre-existing UQ; thus UQ needs to be present as a precursor before RQ can be made. Figure 1 shows the biosynthesis of UQ in yeast and ''E. coli'' where ‘n’ represents the number of isoprene units between various organisms. Dimethylallyl diphosphate A and isopentyl diphosphate B come together to form polyisoprenyl diphosphate C. With the addition of p-hydroxybenzoic acid, the product that arises is 3-polyprenyl-4-hydroxybenzoic acid D. The next three steps of synthesis varies between different organisms, but molecule E is made across all organisms and through oxidation, demethyldemethoxyubiquinone (DDMQ) is eventually formed. RQ has been theorized to be synthesized from DDMQn, DMQn, DMeQn, or UQn, as shown with the dashed arrows. Recent studies have shown that Path 4 - RQ biosynthesis via UQ, is the favored route. It has been further shown that the gene ''rquA'' is required for the biosynthesis of RQ in ''R. rubrum'', and that RquA catalyzes the conversion of UQ to RQ. The RquA protein uses ''S''-adenosyl-''L''-methionine as the amino donor to convert UQ to RQ in an unusual Mn(II)-catalyzed reaction.
Research in ''C. elegans'' has shown an alternative path for production of RQ. Even after knocking out all UQ production, RQ is still present within those mutant strains. Based on this data, RQ production is not solely based on UQ-like molecules and instead can be made via tryptophan metabolites. Therefore, the amino group that is added in late stages of RQ biosynthesis in ''rquA''-containing species is instead present throughout intermediate stages of RQ biosynthesis in ''C. elegans''. With this proposed biosynthesis, the kynurenine pathway still needs to be upregulated, and activity from certain genes like ''kynu-1'' which encodes for the KYNU-1 enzyme that catalyzes production of 3-hydroxy-L-kynurenine to 3-hydroxyanthranilic acid, needs to be upheld. Recent work has revealed that alternative splicing of the ''coq-2'' polyprenyltransferase gene controls the level of RQ in animals. Animals that produce RQ (e.g. ''C. elegans'' and helminth parasites) contain both COQ-2 protein isoforms (COQ-2a and COQ-2e), and COQ-2e catalyzes prenylation of 3-hydroxyanthranilic acid (instead of p-hydroxybenzoic acid) which leads to RQ.
ubiquinone
Coenzyme Q, also known as ubiquinone and marketed as CoQ10, is a coenzyme family that is ubiquitous in animals and most bacteria (hence the name ubiquinone). In humans, the most common form is coenzyme Q10 or ubiquinone-10.
It is a 1,4-benzoq ...
-like molecule
A molecule is a group of two or more atoms held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions which satisfy this criterion. In quantum physics, organic chemistry, and bioch ...
that is an important cofactor used in anaerobic
Anaerobic means "living, active, occurring, or existing in the absence of free oxygen", as opposed to aerobic which means "living, active, or occurring only in the presence of oxygen." Anaerobic may also refer to:
* Anaerobic adhesive, a bonding a ...
energy metabolism
Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...
by many organisms. Recently, it has gained attention as a potential anthelmintic
Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. They may a ...
drug target due to the fact that parasitic hosts do not synthesize or use this cofactor. Because this cofactor is used in low oxygen environments, many helminth-like organisms have adapted to survive host environments such as the areas within the gastrointestinal tracks.
Biosynthesis
Currently the biosynthesis of rhodoquinone (RQ) is still being debated, but there are two main biosynthetic pathways that are being researched. The first pathway requires the organism to produce ubiquinone (UQ) before the amino group can be added onto the quinone ring. The second pathway allows RQ to be synthesized without any UQ being present by using tryptophan metabolites instead.
In the case of the prokaryotic organism ''R. rubrum'', RQ has been shown to be synthesized by addition of an amino group to a pre-existing UQ; thus UQ needs to be present as a precursor before RQ can be made. Figure 1 shows the biosynthesis of UQ in yeast and ''E. coli'' where ‘n’ represents the number of isoprene units between various organisms. Dimethylallyl diphosphate A and isopentyl diphosphate B come together to form polyisoprenyl diphosphate C. With the addition of p-hydroxybenzoic acid, the product that arises is 3-polyprenyl-4-hydroxybenzoic acid D. The next three steps of synthesis varies between different organisms, but molecule E is made across all organisms and through oxidation, demethyldemethoxyubiquinone (DDMQ) is eventually formed. RQ has been theorized to be synthesized from DDMQn, DMQn, DMeQn, or UQn, as shown with the dashed arrows. Recent studies have shown that Path 4 - RQ biosynthesis via UQ, is the favored route. It has been further shown that the gene ''rquA'' is required for the biosynthesis of RQ in ''R. rubrum'', and that RquA catalyzes the conversion of UQ to RQ. The RquA protein uses ''S''-adenosyl-''L''-methionine as the amino donor to convert UQ to RQ in an unusual Mn(II)-catalyzed reaction.
Research in ''C. elegans'' has shown an alternative path for production of RQ. Even after knocking out all UQ production, RQ is still present within those mutant strains. Based on this data, RQ production is not solely based on UQ-like molecules and instead can be made via tryptophan metabolites. Therefore, the amino group that is added in late stages of RQ biosynthesis in ''rquA''-containing species is instead present throughout intermediate stages of RQ biosynthesis in ''C. elegans''. With this proposed biosynthesis, the kynurenine pathway still needs to be upregulated, and activity from certain genes like ''kynu-1'' which encodes for the KYNU-1 enzyme that catalyzes production of 3-hydroxy-L-kynurenine to 3-hydroxyanthranilic acid, needs to be upheld. Recent work has revealed that alternative splicing of the ''coq-2'' polyprenyltransferase gene controls the level of RQ in animals. Animals that produce RQ (e.g. ''C. elegans'' and helminth parasites) contain both COQ-2 protein isoforms (COQ-2a and COQ-2e), and COQ-2e catalyzes prenylation of 3-hydroxyanthranilic acid (instead of p-hydroxybenzoic acid) which leads to RQ.
References
{{Reflist, 30em Chemical substances Molecules Cofactors Metabolism