Syntheses of deuterium labeled prenyldiphosphate and prenylcysteine analogues for <i>in vivo</i> mass spectrometric quantification

Subramanian, Thangaiah; Subramanian, Karunai Leela; Sunkara, Manjula; Onono, Fredrick O.; Morris, Andrew J.; Spielmann, H. Peter

doi:10.1002/jlcr.3049

Cited by 4 publications

(1 citation statement)

References 39 publications

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“…Although the extraction protocol for the HPLC-MS/MS based method already incorporated internal standards that are similar to prenyl diphosphates, the most reliable means of quantification would be stable isotope labeled compounds (Stokvis et al 2005). Fortunately, a procedure for chemical synthesis of hexadeuterated FDP and GGDP was recently published, which would be useful in supplying standards for such more reliable quantification of prenyl diphosphates in vivo (Subramanian et al 2013).…”

Section: Analytical Measurement Of Prenyl Diphosphate Products In Vitmentioning

confidence: 99%

Isoprenyl diphosphate synthases: the chain length determining step in terpene biosynthesis

Nagel

Schmidt

Peters

2018

Planta

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Main Conclusion This review summarizes the recent developments in the study of isoprenyl diphosphate synthases with an emphasis on analytical techniques, product length determination, and the physiological consequences of manipulating expression in planta. The highly diverse structures of all terpenes are synthesized from the five carbon precursors dimethylallyl diphosphate and a varying number of isopentenyl diphosphate units through 1'-4 alkylation reactions. These elongation reactions are catalyzed by isoprenyl diphosphate synthases (IDS). IDS are classified depending on the configuration of the ensuing double bond as transand cis-IDS. In addition, IDS are further stratified by the length of their prenyl diphosphate product. This review discusses analytical techniques for the determination of product length and the factors that control product length, with an emphasis on alternative mechanisms. With recent advances in analytics, multiple IDS of Arabidopsis thaliana have been recently reinvestigated and demonstrated to yield products of different lengths than originally reported, which is summarized here. As IDS dictate prenyl diphosphate length and thereby which class of terpenes is ultimately produced, another focus of this review is the impact that altering IDS expression has on terpenoid natural product accumulation. Finally, recent findings regarding the ability of a few IDS to not catalyze 1'-4 alkylation reactions, but instead produce irregular products, with unusual connectivity, or act as terpene synthases, are also discussed.

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Section: Analytical Measurement Of Prenyl Diphosphate Products In Vitmentioning

confidence: 99%

Isoprenyl diphosphate synthases: the chain length determining step in terpene biosynthesis

Nagel

Schmidt

Peters

2018

Planta

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Synthesis of Isotopically Labelled Oligoprenyl Diphosphates and Their Application in Mechanistic Investigations of Terpene Cyclases

et al. 2014

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A flexible, efficient and robust method for the synthesis of isotopically labelled oligoprenyl diphosphates was developed. The method makes use of just a few building blocks (acetone, triethyl phosphonoacetate, and ethyl acetoacetate) from which several isotopomers with deuterium or 13C‐labelling are commercially available or can be easily obtained by synthesis. Besides these building blocks, a few deuterated reagents were used for the introduction of deuterium labelling. Furthermore, the synthesis of [14‐2H]geranylgeranyl diphosphate is reported. The material was used for a stereochemical analysis of the cyclisation reaction catalysed by tuberculosinyl diphosphate synthase from Mycobacterium tuberculosis.

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Efficient Use of Exogenous Isoprenols for Protein Isoprenylation by MDA-MB-231 Cells Is Regulated Independently of the Mevalonate Pathway

Onono

Subramanian

Sunkara

et al. 2013

Journal of Biological Chemistry

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Background: Stable isotope/chemical probe mass spectrometry was used to monitor cancer cell metabolism of exogenous isoprenols. Results: Efficient use of exogenous isoprenols for protein isoprenylation was undiminished by genetic or pharmacological inhibition of HMG-CoA reductase. Conclusion: Exogenous isoprenols are metabolized independently of the mevalonate pathway. Significance: This study identifies and quantitates a pathway of isoprenol metabolism with potential relevance to cancer progression.

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Syntheses of deuterium labeled prenyldiphosphate and prenylcysteine analogues for in vivo mass spectrometric quantification

Cited by 4 publications

References 39 publications

Isoprenyl diphosphate synthases: the chain length determining step in terpene biosynthesis

Isoprenyl diphosphate synthases: the chain length determining step in terpene biosynthesis

Synthesis of Isotopically Labelled Oligoprenyl Diphosphates and Their Application in Mechanistic Investigations of Terpene Cyclases

Efficient Use of Exogenous Isoprenols for Protein Isoprenylation by MDA-MB-231 Cells Is Regulated Independently of the Mevalonate Pathway

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