Identification of regulatory sites in the biosynthesis of ubiquinone in the perfused rat heart

Yamamoto, Toshinori; Shimizu, Shun-Ichi; Hiromi, Sugawara; Momose, Kazutaka; Rudney, Harry

doi:10.1016/0003-9861(89)90089-1

Cited by 15 publications

(2 citation statements)

References 8 publications

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“…These enzymes are also probably organized as a complex in animal tissues. The accumulation of polyprenyl-4-hydroxybenzoate as an intermediate both in perfused beating rat heart and in mitochondria prepared from rat heart supports this hypothesis [28,29].…”

Section: Discussionmentioning

confidence: 76%

Isolation and functional expression of human COQ2, a gene encoding a polyprenyl transferase involved in the synthesis of CoQ

Forsgren

Attersand

Lake

et al. 2004

Biochemical Journal

111

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The COQ2 gene in Saccharomyces cerevisiae encodes a Coq2 (p-hydroxybenzoate:polyprenyl transferase), which is required in the biosynthetic pathway of CoQ (ubiquinone). This enzyme catalyses the prenylation of p-hydroxybenzoate with an all-trans polyprenyl group. We have isolated cDNA which we believe encodes the human homologue of COQ2 from a human muscle and liver cDNA library. The clone contained an open reading frame of length 1263 bp, which encodes a polypeptide that has sequence homology with the Coq2 homologues in yeast, bacteria and mammals. The human COQ2 gene, when expressed in yeast Coq2 null mutant cells, rescued the growth of this yeast strain in the absence of a non-fermentable carbon source and restored CoQ biosynthesis. However, the rate of CoQ biosynthesis in the rescued cells was lower when compared with that in cells rescued with the yeast COQ2 gene. CoQ formed when cells were incubated with labelled decaprenyl pyrophosphate and nonaprenyl pyrophosphate, showing that the human enzyme is active and that it participates in the biosynthesis of CoQ.

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Section: Discussionmentioning

confidence: 76%

Isolation and functional expression of human COQ2, a gene encoding a polyprenyl transferase involved in the synthesis of CoQ

Forsgren

Attersand

Lake

et al. 2004

Biochemical Journal

111

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“…Intermediate 2 is the predominant intermediate in wild-type E. coli grown anaerobically and is also present to a lesser extent in wild-type cells under aerobic conditions (Alexander & Young, 1978;Gibson & Young, 1978). In rat and yeast, compound 1 is the predominant intermediate (Yamamoto et al, 1989(Yamamoto et al, , 1990Kang et al, 1991;Poon et al, 1995). The accumulation of intermediate 2 in E. coli and 1 in eukaryotic cells has been interpreted as indicating that the first hydroxylase is ratelimiting or may indicate a high K m of this hydroxylase for one of its substrates (Poon et al 1995).…”

Section: O-methylation Steps In Ubiquinone Biosynthesismentioning

confidence: 99%

Complementation of coq3 Mutant Yeast by Mitochondrial Targeting of the Escherichia coli UbiG Polypeptide: Evidence That UbiG Catalyzes Both O-Methylation Steps in Ubiquinone Biosynthesis

et al. 1996

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Ubiquinone functions in the mitochondrial electron transport chain. Recent evidence suggests that the reduced form of ubiquinone (ubiquinol) may also function as a lipid soluble antioxidant. The biosynthesis of ubiquinone requires two O-methylation steps. In eukaryotes, the first O-methylation step is carried out by the Coq3 polypeptide, which catalyzes the transfer of a methyl group from S-adenosylmethionine to 3,4-dihydroxy-5-polyprenylbenzoate. In Escherichia coli, 2-polyprenyl-6-hydroxyphenol is the predicted substrate; however, the corresponding O-methyltransferase has not been identified. The second O-methylation step in E. coli, the conversion of demethylubiquinone to ubiquinone, is carried out by the UbiG methyltransferase, which is 40% identical in amino acid sequence with the yeast Coq3 methyltransferase. On the basis of the chemical similarity of the first and last methyl-acceptor substrates and the high degree of amino acid sequence identity between Coq3p and UbiG, the ability of UbiG to catalyze both O-methylation steps was investigated. The current study shows that the ubiG gene is able to restore respiration in the yeast coq3 mutant, provided ubiG is modified to contain a mitochondrial leader sequence. The mitochondrial targeting of O-methyltransferase activity is an essential feature of the ability to restore respiration and hence ubiquinone biosynthesis in vivo. In vitro import assays show the mitochondrial leader sequence present on Coq3p functions to direct mitochondrial import of Coq3p in vitro and that processing to the mature form requires a membrane potential. In vitro methyltransferase assays with E. coli cell lysates and synthetically prepared farnesylated-substrate analogs indicate that UbiG methylates both the derivative of the eukaryotic intermediate, 3,4-dihydroxy-5-farnesylbenzoate, as well as that of the E. coli intermediate, 2-farnesyl-6-hydroxyphenol. The data presented indicate that the yeast Coq3 polypeptide is located in the mitochondria and that E. coli UbiG catalyzes both O-methylation steps in E. coli.

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Possible involvement of 3-hydroxymethylglutaryl-CoA reductase in determining the side-chain length of ubiquinone in rat heart

Shimizu

Yamamoto

Hiromi

et al. 1991

Archives of Biochemistry and Biophysics

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Identification of regulatory sites in the biosynthesis of ubiquinone in the perfused rat heart

Cited by 15 publications

References 8 publications

Isolation and functional expression of human COQ2, a gene encoding a polyprenyl transferase involved in the synthesis of CoQ

Isolation and functional expression of human COQ2, a gene encoding a polyprenyl transferase involved in the synthesis of CoQ

Complementation of coq3 Mutant Yeast by Mitochondrial Targeting of the Escherichia coli UbiG Polypeptide: Evidence That UbiG Catalyzes Both O-Methylation Steps in Ubiquinone Biosynthesis

Possible involvement of 3-hydroxymethylglutaryl-CoA reductase in determining the side-chain length of ubiquinone in rat heart

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