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Theobromine

About: Theobromine is a research topic. Over the lifetime, 1137 publications have been published within this topic receiving 29723 citations. The topic is also known as: 3,7-Dimethylxanthine & Theobromin.


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Journal ArticleDOI
TL;DR: The structures of two S-adenosyl-l-methionine-dependent N-methyltransferases that mediate caffeine biosynthesis in C. canephora ‘robusta’, xanthosine (XR) methyltransferase (XMT), and 1,7-dimethylxanthine methyl transferase (DXMT) are described.
Abstract: Caffeine (1,3,7-trimethylxanthine) is a secondary metabolite produced by certain plant species and an important component of coffee (Coffea arabica and Coffea canephora) and tea (Camellia sinensis). Here we describe the structures of two S-adenosyl-l-methionine-dependent N-methyltransferases that mediate caffeine biosynthesis in C. canephora ‘robusta’, xanthosine (XR) methyltransferase (XMT), and 1,7-dimethylxanthine methyltransferase (DXMT). Both were cocrystallized with the demethylated cofactor, S-adenosyl-l-cysteine, and substrate, either xanthosine or theobromine. Our structures reveal several elements that appear critical for substrate selectivity. Serine-316 in XMT appears central to the recognition of XR. Likewise, a change from glutamine-161 in XMT to histidine-160 in DXMT is likely to have catalytic consequences. A phenylalanine-266 to isoleucine-266 change in DXMT is also likely to be crucial for the discrimination between mono and dimethyl transferases in coffee. These key residues are probably functionally important and will guide future studies with implications for the biosynthesis of caffeine and its derivatives in plants.

97 citations

Journal ArticleDOI
TL;DR: It is imperative that a major research program be undertaken to evaluate these methylxanthines and, of course, cocoa, coffee, and tea, and it only will be through elucidating their mechanism of action that the authors will be in a position to assess their safety.
Abstract: The critical review of the literature cited on pharmacology, toxicology, metabolism, and safety assessment clearly demonstrates that cocoa per se has not attracted a great deal of scientific interest because of its long-term usage with no reported adverse effects that would be injurious to man. On the other hand, a great deal of research has been directed towards understanding the pharmacological properties of the methylxanthines--caffeine, theobromine, and theophylline. Much of the emphasis on metabolism, toxicology, teratogenic potential, and safety assessment has been on the evaluation of caffeine. In light of the serious health concerns ascribed to the effects of caffeine and the lack of basic information on theobromine and theophylline, it is imperative that a major research program be undertaken to evaluate these methylxanthines and, of course, cocoa, coffee, and tea. It only will be through elucidating their mechanism of action that we will be in a position to assess their safety. Before committing research efforts to evaluating the long-term effects of these methylxanthines and their respective foodstuffs, which serve as our primary source of exposure, it is critical to initiate more basic research on the metabolism of caffeine, theophylline, and theobromine in several animal species and man. While published reports do appear in this area, it is essential to understand fully the similarities and differences between various animals and man. The influence of dietary factors and drug interactions must also be determined. Before establishing dosage levels for a chronic toxicity study, the pharmacokinetics of the dose must be determined in the species that will be used in long-term studies. This is necessary if there is a dose-dependency in the animal above which saturation may occur and the plasma half-life kinetics change, or shifts occur either in the metabolic pathways of degradation and/or in the route of excretion from the body. The area of teratology must also be thoroughly evaluated. Studies undertaken should include identification and quantitation of the metabolites of caffeine, theophylline, and theobromine in the pregnant animal, the respective pharmacokinetics of each compound, dose-dependency (if this is the case), and their potential teratogenicity. In addition, the influence of other drugs or dietary variables must be included. In addition to teratology, a great deal of research is needed to assess and quantitate fetal and neonatal metabolism of these compounds.(ABSTRACT TRUNCATED AT 400 WORDS)

97 citations

Journal ArticleDOI
TL;DR: It is shown that the determination of purines in serum and saliva samples, including therapeutic concentrations of caffeine and theophylline, can be accomplished without any sample pretreatment, whereas sample extraction is required for the determination on-column multi-wavelength detection.

95 citations

Journal ArticleDOI
TL;DR: In this article, the authors reported the isolation of a bifunctional coffee caffeine synthase (CCS1) clone from coffee endosperm by reverse transcription-polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends (RACE) technique.

94 citations

Journal ArticleDOI
TL;DR: Low dose caffeine exposure (plasma levels corresponding to umbilical cord plasma in newborns of coffee-consuming mothers) reduced HI brain damage by 30% in 7-d-old rats, and this ameliorating effect could not be accounted for by up-regulation of adenosine receptors.
Abstract: There is considerable concern over the widespread use of caffeine during and after pregnancy. We have therefore examined the effect of perinatal caffeine use on the vulnerability of the immature brain to hypoxic ischemia (HI). Rat pups were exposed to caffeine during the first 7 d after birth by addition of a low or a high dose (0.3 or 0.8 g/L) of caffeine to the drinking water of their dams. At 7 d the pups were exposed to unilateral carotid occlusion+exposure to 7.70% oxygen for 100 min. The extent of HI brain damage was evaluated 2 wk after the insult. The effects of caffeine on A1 and A2a receptors, A1 mRNA and A2a mRNA, were examined by receptor autoradiography and in situ hybridization. Caffeine, theobromine, theophylline, and paraxanthine were analyzed in plasma of separate animals. Exposure to caffeine reduced HI brain damage from 40.3 +/- 3.2% in controls to 29.8 +/- 4.0% (p < 0.05) in low dose and 33.7 +/- 3.9% (NS) in the high dose group. The A1 receptor density measured as [3H]-1,3-dipropyl-8-cyclopentyl xanthine ([3H]-DPCPX) binding was not significantly affected after low dose caffeine but increased in the brain of rat pups in the high dose group. The A2a receptor density measured as [3H]-2[p-(2-carbonylethyl)-phenethylamino]-5'-N- ethylcarboxamidoadenosine ([3H]-CGS 21680) binding and the expression of A1 mRNA and A2a mRNA were not altered by caffeine treatment. In conclusion, low dose caffeine exposure (plasma levels corresponding to umbilical cord plasma in newborns of coffee-consuming mothers) reduced HI brain damage by 30% in 7-d-old rats.(ABSTRACT TRUNCATED AT 250 WORDS)

94 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
202339
202288
202122
202036
201937
201840