The DOI matches its Crossref record.
Biotransformation of caffeine, paraxanthine, theobromine and theophylline by cDNA-expressed human CYP1A2 and CYP2E1
Abstract
Six human cytochrome P450s expressed in HepG2 cells using vaccinia virus cDNA-directed expression, were used to study the biotransformation of caffeine and its metabolites. CYP1A2 alone was responsible for caffeine 3-demethylation and paraxanthine 7-demethylation; in addition, 1A2 catalysed virtually all reactions related to caffeine and its metabolites. The metabolic profile of caffeine biotransformation by CYP1A2 averaged 81.5% for paraxanthine, 10.8% for theobromine and 5.4% for theophylline formation. It remained quite uniform when caffeine concentrations were varied. The most striking finding was that CYP2E1 (the ethanol-inducible form) had major influences upon caffeine metabolism: in particular, it catalysed the formation of theophylline and theobromine from caffeine. Thus, the in vivo metabolite profiling of caffeine may reveal CYP2E1 activities in addition to the previously documented activities of CYP1A2, polymorphic N-acetyltransferase and xanthine oxidase.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cited by
Interindividual Differences in Caffeine Metabolism and Factors Driving Caffeine Consumption
Nehlig, A. (2018) · Pharmacological Reviews · doi:10.1124/pr.117.014407 · Cited by 632
Coffee, CYP1A2 genotype, and risk of myocardial infarction
Cornelis, M. C., El-Sohemy, A., Kabagambe, E. K., & Campos, H. (2006) · JAMA · doi:10.1001/jama.295.10.1135 · Cited by 490
Pharmacokinetics and metabolism of natural methylxanthines in animal and man
Arnaud, M. J. (2011) · Handbook of experimental pharmacology · doi:10.1007/978-3-642-13443-2_3 · Cited by 259
CYP1A2 genotype modifies the association between coffee intake and the risk of hypertension
Palatini, P., Ceolotto, G., Ragazzo, F., Dorigatti, F., Saladini, F., Papparella, I., Mos, L., Zanata, G., & Santonastaso, M. (2009) · Journal of Hypertension · doi:10.1097/hjh.0b013e32832ba850 · Cited by 230
Cornelis, M. C., Kacprowski, T., Menni, C., Gustafsson, S., Pivin, E., Adamski, J., Artati, A., Eap, C. B., Ehret, G., Friedrich, N., et al. (2016) · Human Molecular Genetics · doi:10.1093/hmg/ddw334 · Cited by 175
What Should We Do about Habitual Caffeine Use in Athletes?
Pickering, C., & Kiely, J. (2019) · Sports Medicine · doi:10.1007/s40279-018-0980-7 · Cited by 127
Doepker, C., Lieberman, H. R., Smith, A. P., Peck, J. D., El-Sohemy, A., & Welsh, B. T. (2016) · Annual Review of Food Science and Technology · doi:10.1146/annurev-food-041715-033243 · Cited by 87
The Role of Genetics in Moderating the Inter-Individual Differences in the Ergogenicity of Caffeine
Southward, K., Rutherfurd-Markwick, K., Badenhorst, C., & Ali, A. (2018) · Nutrients · doi:10.3390/nu10101352 · Cited by 81
Grgic, J., Pickering, C., Bishop, D. J., Schoenfeld, B. J., Mikulic, P., & Pedisic, Z. (2020) · Journal of the International Society of Sports Nutrition · doi:10.1186/s12970-020-00349-6 · Cited by 60
Dik, V. K., Bueno-de-Mesquita, H. B., Van Oijen, M. G. H., Siersema, P. D., Uiterwaal, C. S. P. M., Van Gils, C. H., Van Duijnhoven, F. J. B., Cauchi, S., Yengo, L., Froguel, P., et al. (2014) · International Journal of Cancer · doi:10.1002/ijc.28655 · Cited by 40
Biological sex differences in pharmacokinetics and adverse drug reactions
Aljohmani, A., & Yildiz, D. (2026) · Naunyn-Schmiedeberg's Archives of Pharmacology · doi:10.1007/s00210-025-04721-8 · Cited by 35
Coffee Consumption and the Risk of Cancer in the Norwegian Women and Cancer (NOWAC) Study
Lukic, M., Licaj, I., Lund, E., Skeie, G., Weiderpass, E., & Braaten, T. (2016) · European Journal of Epidemiology · doi:10.1007/s10654-016-0142-x · Cited by 35
Influence of carbohydrate on serum caffeine concentrations following caffeine ingestion
Skinner, T. L., Jenkins, D. G., Folling, J., Leveritt, M. D., Coombes, J. S., & Taaffe, D. R. (2013) · Journal of Science and Medicine in Sport · doi:10.1016/j.jsams.2012.08.004 · Cited by 27
Caffeine, CYP1A2 Genotype, and Exercise Performance: A Systematic Review and Meta-Analysis
BARRETO, G., ESTEVES, G. P., MARTICORENA, F., OLIVEIRA, T. N., GRGIC, J., & SAUNDERS, B. (2024) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000003313 · Cited by 27
Montalvo‐Alonso, J. J., del Val‐Manzano, M., Martín‐Rivas, I., Ferragut, C., Valadés, D., & Pérez‐López, A. (2026) · Scandinavian Journal of Medicine & Science in Sports · doi:10.1111/sms.70214 · Cited by 5
Metadata
- Authors
- Gu, L., Gonzalez, F. J., Kalow, W., & Tang, B. K.
- Venue
- Pharmacogenetics
- Published
- 1992-04
- Volume
- 2
- Issue
- 2
- Pages
- 73-77
- ISSN
- 0960-314X (ISSN-L)
- OpenAlex
- W2068847386
- Cited by
- 326
- References
- 0
- FWCI
- 10.37
- Type
- journal article
- Language
- en
- Open access
- closed
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
