O(2),1,9-trimethyluric acid and 1,3,7,9-tetramethyluric acid in leaves of different Coffea species

doi:10.1016/0031-9422(75)83027-5

Phytochemistry

Volume 14, Issue 3, March 1975, Pages 747-750

https://doi.org/10.1016/0031-9422(75)83027-5 Get rights and content

Abstract

O(2),1,9-Trimethyluric acid and 1,3,7,9-tetramethyluric acid were isolated from young leaves of Coffea liberica, C. arnoldiana, C. dewevrei var. excelsa and var. aruwimiensis. The first purine has not been found before in nature; its identification required the synthesis of nearly all of its possible isomers.

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Development of a liquid chromatography-tandem mass spectrometry (LC–MS/MS) method for characterizing caffeine, methylliberine, and theacrine pharmacokinetics in humans
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Citation Excerpt :
Subsequently, methylliberine was first identified in very low concentrations (<0.1%) during vegetative development of C. liberica leaves [3]. Mature leaves of C. liberica, C. dewevrei, and C. abeokutae contain the methylurates theacrine, methylliberine, and liberine [2], whereas the leaves of C. assamica var. kucha contain only theacrine [4].
Coffea liberica possesses stimulant properties without accumulating the methylxanthine caffeine. The basis for this peculiar observation is that methylurates (e.g., theacrine and methylliberine) have replaced caffeine. The stimulant properties of methylurates, alone and in combination with caffeine, have recently been investigated. However, human pharmacokinetics and LC-MS/MS methods for simultaneous measurement of methylxanthines and methylurates are lacking. To address this deficiency, we conducted a pharmacokinetic study in which subjects (n = 12) were orally administered caffeine (150 mg), methylliberine (Dynamine™, 100 mg), and theacrine (TeaCrine®, 50 mg) followed by blood sampling over 24 h. Liquid-liquid extraction of plasma samples containing purine alkaloids and internal standard (¹³C-Caffeine) were analyzed using a C18 reversed-phase column and gradient elution (acetonitrile and water, both containing 0.1% formic acid). A Waters Xevo TQ-S tandem mass spectrometer (positive mode) was used to detect caffeine, methylliberine, theacrine, and IS transitions of m/z 195.11 → 138.01, 225.12 → 168.02, 225.12 → 167.95, and 198.1 → 140.07, respectively. The method was validated for precision, accuracy, selectivity, and linearity and was successfully applied to characterize the oral pharmacokinetics of caffeine, methylliberine, and theacrine in human plasma. Successful development and application of LC-MS/MS-based methods such as ours for the simultaneous measurement of methylxanthines and methylurates are essential for the characterization of potential pharmacokinetic and pharmacodynamic interactions.
Theacrine (1,3,7,9-tetramethyluric acid) synthesis in leaves of a Chinese tea, kucha (Camellia assamica var. kucha)
2002, Phytochemistry
Theacrine (1,3,7,9-tetramethyluric acid) and caffeine were the major purine alkaloids in the leaves of an unusual Chinese tea known as kucha (Camellia assamica var. kucha). Endogenous levels of theacrine and caffeine in expanding buds and young leaves were ca. 2.8 and 0.6–2.7% of the dry wt, respectively, but the concentrations were lower in the mature leaves. Radioactivity from S-adenosyl-l-[methyl-¹⁴C]methionine was incorporated into theacrine as well as theobromine and caffeine by leaf disks of kucha, indicating that S-adenosyl-l-methionine acts as the methyl donor not only for caffeine biosynthesis but also for theacrine production. [8-¹⁴C]Caffeine was converted to theacrine by kucha leaves with highest incorporation occurring in expanding buds. When [8-¹⁴C]adenosine, the most effective purine precursor for caffeine biosynthesis in tea (Camellia sinensis), was incubated with young kucha leaves for 24 h, up to 1% of total radioactivity was recovered in theacrine. However, pulse-chase experiments with [8-¹⁴C]adenosine demonstrated much more extensive incorporation of label into caffeine than theacrine, possibly because of dilution of [¹⁴C]caffeine produced by the large endogenous caffeine pool. These results indicate that in kucha leaves theacrine is synthesized from caffeine in what is probably a three-step pathway with 1,3,7-methyluric acid acting an intermediate. This is a first demonstration that theacrine is synthesized from adenosine via caffeine.
Biosynthesis and Metabolism of Caffeine and Related Purine Alkaloids in Plants
1999, Advances in Botanical Research
This chapter discusses the biosynthesis and metabolism of caffeine and related purine alkaloids in plants. Caffeine and other purine alkaloids, including theobromine and theophylline, have played a major role in the long-standing popularity of non-alcoholic beverages and foods such as coffee, tea, cocoa, mate, chocolate and a wide range of soft drinks. This chapter begins by summarizing those aspects of general purine metabolism in plants that are related to purine alkaloid metabolism, and then provides an up-to-date account of the biosynthesis of caffeine and theobromine in a variety of plant species. Recent information on the properties and isolation of key enzymes, such as the caffeine synthase, are presented. Physiological studies on caffeine biosynthesis in tea and coffee plants including the authors' own work are also introduced. Catabolism of caffeine via demethylation to xanthine and degradation via the purine catabolism pathway in higher plants is then reviewed. The diversity of caffeine catabolism between species and between tissues of different age is considered. In young tea leaves, theophylline, a catabolite of caffeine, is reutilized for caffeine synthesis, but in aged Coffea arabica leaves 7-methylxanthine accumulates.
Purine alkaloid distribution withinHerrania andTheobroma
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Purine and purine alkaloid metabolism in Camellia and Coffea plants
1992, Phytochemistry
The metabolism of purine nucleotides and purine alkaloids (e.g. caffeine and theobromine) are reviewed in tea and coffee plants. Purine metabolism in these plants is similar to that in other plants, which do not contain caffeine; however, tea and coffee plants have purine nucleotides, including those produced directly by the pathway of purine biosynthesis de novo, as effective precursors of caffeine. Xanthosine is the first methyl acceptor from S-adenosylmethionine in caffeine biosynthesis, and is also metabolized by a purine degradation pathway via xanthine. The regulation of purine alkaloid biosynthesis remains elusive, but the activity of the three N-methyltransferases is considered. The production and accumulation of the alkaloids are associated with the developmental stage of tissues (i.e. leaves, flowers, fruits and seeds) and with seasonal changes, especially in tea grown in temperate climates. The metabolism (especially biosynthesis) of purine alkaloids differs among Camellia species. In Coffea plants and in cultured cells, the rate of caffeine synthesis and turnover (i.e. biodegradation and/or biotransformation to xanthine or to methyluric acids) differs markedly among species. Ecological roles of the alkaloids have been reported, but their physiological significance in tea and coffee plants remains uncertain.
Chlorogenic acids and caffeine as possible taxonomic criteria in Coffea and Psilanthus
1989, Phytochemistry
This paper reports the amount of chlorogenic acids, chlorogenic acid-like components, caffeine and other 276 nm-absorbing components in seeds of Coffea and Psilanthus. Twenty species have been grouped according to their seed composition and the groupings compared critically with the existing classification scheme based upon morphology. Concordance is generally good, although classification on seed composition suggests that Coffea subgen. Coffea could be further subdivided and that Psilanthus subgen. Afrocoffea may merit recognition at generic rather than subgeneric level. It also appears that such analyses may provide a better understanding of the morphologically variable taxa such as C. congensis, C. stenophylla and the libero-excelsoides group.

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O(2),1,9-trimethyluric acid and 1,3,7,9-tetramethyluric acid in leaves of different Coffea species

Abstract

J. Biol. Chem.

C.R. Acad. Sci.

J. Am. Chem. Soc.

Toxicol. Appl. Pharm.

Experientia

Nature

J. Prakt. Chem.

Ber. Deutsch. Chem. Ges.