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.

Occurrence of theobromine synthase genes in purine alkaloid-free species of Camellia plants

Abstract: Caffeine (1,3,7-trimethylxanthine) and theobromine (3,7-dimethylxanthine) are purine alkaloids that are present in high concentrations in plants of some species of Camellia. However, most members of the genus Camellia contain no purine alkaloids. Tracer experiments using [8-(14)C]adenine and [8-(14)C]theobromine showed that the purine alkaloid pathway is not fully functional in leaves of purine alkaloid-free species. In five species of purine alkaloid-free Camellia plants, sufficient evidence was obtained to show the occurrence of genes that are homologous to caffeine synthase. Recombinant enzymes derived from purine alkaloid-free species showed only theobromine synthase activity. Unlike the caffeine synthase gene, these genes were expressed more strongly in mature tissue than in young tissue.

The Xanthine Content of Guarana and Its Preparations

Abstract: The Identity Of Caffeine As The Major Xanthine Present In Guarana Has Been Confirmed By Spectroscopic Methods. Theobromine and Theophylline Were Present In Small Amounts But The Presence Of A Tetramethylxanthine Could Not Be Detected. Evidence Was Obtained For The Presence Of A Complex Of Caffeine and A Tannin. Hplc Was Used To Quantify The Caffeine Present In Various Samples Of Guarana and Its Products. The Amount Of Caffeine Present Was Found To Be Between 2.0 and 4.5% W/W Which Is Of The Same Order As That Present In Tea and Coffee.

Conversion of Xanthosine into Caffeine in Tea Plants

Abstract: 14C-labelled methionine, xanthosine, and 7-methylxan-thosine were given to excised tea shoots. The methyl group of methionine was incorporated into 7-methylxanthosine (ca. 10%) in the earlier period of incubation after the uptake. About 50% of the radioactivity of xanthosine was rapidly incorporated into caffeine via 7-methylxanthosine, 7-methylxanthine, and theobromine within 24 hr. 7-Methylxanthosine was also converted into caffeine at a high rate. The results suggest that the pathway for caffeine biosynthesis is as follows: xanthosine → 7-methylxanthosine → 7-methylxanthine → theobromine → caffeine.

Changes in caffeine, lidocaine and trimethadione metabolism in carbon tetrachloride-intoxicated rats as assessed by a "cocktail" study.

Abstract: We investigated the possibility of predicting liver damage from changes in the serum concentrations of caffeine (10 mg/kg), lidocaine (4 mg/kg) and trimethadione (4 mg/kg), which are metabolized catalysed by different cytochrome P450 (P450) and/or are dependent on blood flow, in rats with carbon tetrachloride (CCl4: 0.25 ml/kg)-induced liver injury using a strategy referred to as a “cocktail” study. These 3 probe drugs were simultaneously administered intravenously. The half-lives (t1/2) of caffeine, lidocaine and trimethadione were significantly longer in the CCl4-treated group than in oil-treated controls, but no significant differences were observed in mean apparent volumes of distribution (Vd). Serum total body clearance (CL) values of all three drugs were markedly reduced in CCl4-treated animals. In rats with liver damage, the production of 3 metabolites (theobromine, paraxanthine and theophylline) of caffeine in addition to the only metabolite (dimethadione) of trimethadione after intravenous administration of probe drugs were significantly reduced compared to those of controls. These findings suggest that each probe drug, metabolized by different or partially overlapping P450, is useful in evaluating drug-oxidizing capacity in liver disease.

Effects of phenothiazine neuroleptics on the rate of caffeine demethylation and hydroxylation in the rat liver.

Abstract: The primary metabolic pathways of caffeine are 3-N-demethylation to paraxanthine (CYP1A2), 1-N-demethylation to theobromine and 7-N-demethylation to theophylline (CYP1A2 and other enzymes), and 8-hydroxylation to 1,3,7-trimethyluric acid (CYP3A). The aim of the present study was to investigate the influence of phenothiazine neuroleptics (chlorpromazine, levomepromazine, thioridazine, perazine) on cytochrome P-450 activity measured by caffeine oxidation in rat liver microsomes. The obtained results showed that all the investigated neuroleptics competitively inhibited caffeine oxidation in the rat liver, though their potency to inhibit particular metabolic pathways was not equal. Levomepromazine exerted the most potent inhibitory effect on caffeine oxidation pathways, the effect on 8-hydroxylation being the most pronounced. This indicates inhibition of CYP 1 A2 (inhibition of 3-N- and 1-N-demethylation; Ki = 36 and 32 microM, respectively), CYP3A2 (inhibition of 8-hydroxylations; Ki = 20 microM), and possibly other CYP isoenzymes (inhibition of 7-N-demethylation; Ki = 58 microM) by the neuroleptics. The potency of inhibition of caffeine oxidation by perazine was similar to levomepromazine. Thioridazine was a weaker inhibitor of caffeine 3-N- and 7-N-demethylation, while chlorpromazine was weaker in inhibiting caffeine 1-N- and 7-N-demethylation, compared to levomepromazine. In summary, the obtained results showed that all the investigated neuroleptics had a broad spectra of CYP inhibition in the rat liver. The isoenzymes CYP1A2 and CYP3A2 were distinctly inhibited by all the investigated neuroleptics, while other CYP isoenzymes (CYP2B and/or 2E1) by perazine and levomepromazine. The CYP3A2 inhibition was most pronounced. (Ki = 20-40 microM).