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EcoSal Plus

Domain 3:

Metabolism

Biosynthesis of Menaquinone (Vitamin K) and Ubiquinone (Coenzyme Q)

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  • Authors: R. Meganathan1, and Ohsuk Kwon2
  • Editor: Thomas J. Begley3
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Department of Biological Sciences, Northern Illinois University, DeKalb, IL 60115; 2: Omics and Integration Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 52 Eoeun-dong, Yuseong-gu, Daejeon 305–333, Korea; 3: University at Albany, Rensselear, NY
  • Received 25 September 2007 Accepted 23 December 2008 Published 23 December 2009
  • Address correspondence to R. Meganathan rmeganathan@niu.edu
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  • Abstract:

    and contain the naphthoquinones menaquinone (MK; vitamin K) and demethylmenaquinone and the benzoquinone ubiquinone (coenzyme Q; Q). Both quinones are derived from the shikimate pathway, which has been called a "metabolic tree with many branches." There are two different pathways for the biosynthesis of the naphthoquinones. The vast majority of prokaryotes, including and , and the plants use the -succinylbenzoate pathway, while a minority uses the futalosine pathway. The quinone nucleus of Q is derived directly from chorismate, while that of MK is derived from chorismate via isochorismate. The prenyl side chains of both quinones are from isopentenyl diphosphate formed by the 2--methyl-D-erythritol 4-phosphate (non-mevalonate) pathway and the methyl groups are from -adenosylmethionine. In addition, MK biosynthesis requires 2-ketoglutarate and cofactors ATP, coenzyme A, and thiamine pyrophosphate. Despite the fact that both quinones originate from the shikimate pathway, there are important differences in their biosyntheses. The prenyl side chain in MK biosynthesis is introduced at the penultimate step, accompanied by decarboxylation, whereas in Q biosynthesis it is introduced at the second step, with retention of the carboxyl group. In MK biosynthesis, all the reactions of the pathway up to prenylation are carried out by soluble enzymes, whereas all the enzymes involved in Q biosynthesis except the first are membrane bound. In MK biosynthesis, the last step is a -methylation; in Q biosynthesis, the last step is an -methylation. In Q biosynthesis a second -methylation and -methylation take place in the middle part of the pathway. Despite the fact that Q and MK biosyntheses diverge at chorismate, the -methylations in both pathways are carried out by the same methyltransferase.

  • Citation: Meganathan R, Kwon O. 2009. Biosynthesis of Menaquinone (Vitamin K) and Ubiquinone (Coenzyme Q), EcoSal Plus 2009; doi:10.1128/ecosalplus.3.6.3.3

Key Concept Ranking

Electron Transport System
0.45309034
Multienzyme Complex
0.37014654
Aromatic Amino Acids
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Saccharomyces cerevisiae
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0.45309034

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ecosalplus.3.6.3.3.citations
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/content/journal/ecosalplus/10.1128/ecosalplus.3.6.3.3
2009-12-23
2017-08-22

Abstract:

and contain the naphthoquinones menaquinone (MK; vitamin K) and demethylmenaquinone and the benzoquinone ubiquinone (coenzyme Q; Q). Both quinones are derived from the shikimate pathway, which has been called a "metabolic tree with many branches." There are two different pathways for the biosynthesis of the naphthoquinones. The vast majority of prokaryotes, including and , and the plants use the -succinylbenzoate pathway, while a minority uses the futalosine pathway. The quinone nucleus of Q is derived directly from chorismate, while that of MK is derived from chorismate via isochorismate. The prenyl side chains of both quinones are from isopentenyl diphosphate formed by the 2--methyl-D-erythritol 4-phosphate (non-mevalonate) pathway and the methyl groups are from -adenosylmethionine. In addition, MK biosynthesis requires 2-ketoglutarate and cofactors ATP, coenzyme A, and thiamine pyrophosphate. Despite the fact that both quinones originate from the shikimate pathway, there are important differences in their biosyntheses. The prenyl side chain in MK biosynthesis is introduced at the penultimate step, accompanied by decarboxylation, whereas in Q biosynthesis it is introduced at the second step, with retention of the carboxyl group. In MK biosynthesis, all the reactions of the pathway up to prenylation are carried out by soluble enzymes, whereas all the enzymes involved in Q biosynthesis except the first are membrane bound. In MK biosynthesis, the last step is a -methylation; in Q biosynthesis, the last step is an -methylation. In Q biosynthesis a second -methylation and -methylation take place in the middle part of the pathway. Despite the fact that Q and MK biosyntheses diverge at chorismate, the -methylations in both pathways are carried out by the same methyltransferase.

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Figures

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Figure 1

In the structure of MK, the A ring and B ring of the naphthoquinone are shown.

Citation: Meganathan R, Kwon O. 2009. Biosynthesis of Menaquinone (Vitamin K) and Ubiquinone (Coenzyme Q), EcoSal Plus 2009; doi:10.1128/ecosalplus.3.6.3.3
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Citation: Meganathan R, Kwon O. 2009. Biosynthesis of Menaquinone (Vitamin K) and Ubiquinone (Coenzyme Q), EcoSal Plus 2009; doi:10.1128/ecosalplus.3.6.3.3
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Figure 3

Citation: Meganathan R, Kwon O. 2009. Biosynthesis of Menaquinone (Vitamin K) and Ubiquinone (Coenzyme Q), EcoSal Plus 2009; doi:10.1128/ecosalplus.3.6.3.3
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Figure 4

Each compound in the pathway is identified by its abbreviation and a Roman numeral. CHA, chorismate; ICHA, isochorismate; SS-TPP, succinic semialdehyde-TPP; R, pyrimidine component of TPP; R, CH3; R, CHCH OPO ; SEPHCHC, 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylate; SHCHC, 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate; OSB, -succinylbenzoate; OSB-CoA; -succinylbenzoyl-CoA; DHNA-CoA, 1,4-dihydroxy-2-napththoyl-CoA; DHNA, 1,4-dihydroxy-2-napththoate; DMK-8, demethylmenaquinone (may be initially formed as a quinol); MK-8, menaquinone; SAM, -adenosylmethionine; SAH, -adenosylhomocysteine. The genes encoding the enzymes are shown for each reaction followed by their location on the chromosome in min. The gene encoding the thioesterase for the conversion of DHNA-CoA (compound ) to DHNA (compound ) remains to be identified and is shown as ??.

Citation: Meganathan R, Kwon O. 2009. Biosynthesis of Menaquinone (Vitamin K) and Ubiquinone (Coenzyme Q), EcoSal Plus 2009; doi:10.1128/ecosalplus.3.6.3.3
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Figure 5

Only the thiazole ring of the TPP is shown since it is the active site of the molecule. For R, R, and R see the legend to Fig. 4 . The reactions from () to SEPHCHC () are carried out by and the conversion of SEPHCHC () → SHCHC () is by .

Citation: Meganathan R, Kwon O. 2009. Biosynthesis of Menaquinone (Vitamin K) and Ubiquinone (Coenzyme Q), EcoSal Plus 2009; doi:10.1128/ecosalplus.3.6.3.3
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Figure 6

The conversion of OSB-CoA () to spirodilactone of OSB () is nonenzymatic.

Citation: Meganathan R, Kwon O. 2009. Biosynthesis of Menaquinone (Vitamin K) and Ubiquinone (Coenzyme Q), EcoSal Plus 2009; doi:10.1128/ecosalplus.3.6.3.3
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Figure 7

Each compound in the pathway is identified by a Roman numeral. Under anaerobic conditions, there are alternate hydroxylases for the three enzymes incorporating molecular oxygen (UbiB, UbiH, and UbiF). It should be noted that, in compound (), the chemical numbering system locates the prenyl side chain at the C-3 carbon; in compound () and subsequent intermediates, the prenyl side chain is assigned to C-2. Compounds (), (), and (), are drawn in the quinol form. Some authors draw these structures in the quinone form. For other abbreviations, see the legend to Fig. 4 . The chemical names for the intermediates of the pathway are as follows: (), chorismate; (), 4-hydroxybenzoate; (), 3-octaprenyl-4-hydroxybenzoate; (), 2-octaprenylphenol; (), 2-octaprenyl-6-hydroxyphenol; (), 2-octaprenyl-6-methoxyphenol; (), 2-octaprenyl-6-methoxy-1,4-benzoquinol; (), 2-octaprenyl-3-methyl-6 methoxy-1,4-benzoquinol; (), 2-octaprenyl-3-methyl-5-hydroxy-6-methoxy-1,4-benzoquinol; (), ubiquinol; (), Q, ubiquinone. The conversion of () to () is thought to be nonenzymatic.

Citation: Meganathan R, Kwon O. 2009. Biosynthesis of Menaquinone (Vitamin K) and Ubiquinone (Coenzyme Q), EcoSal Plus 2009; doi:10.1128/ecosalplus.3.6.3.3
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