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Pathway Description
Caffeine Metabolism
Rattus norvegicus
Category:
Metabolite Pathway
Sub-Category:
Metabolic
Created: 2018-08-10
Last Updated: 2023-10-25
Caffeine is obtained from diet including coffee and other beverages and is absorbed in the stomach and small intestine. In the liver, the cytochrome P450 oxidase enzyme system and specifically CYP1A2 metabolizes caffeine into paraxanthine to increase lipolysis and increase free fatty acids and glycerol levels in the blood, theobromine to dilate blood vessels and increase urine volume and theophylline which relaxes bronchi smooth muscles. In the lysosome, these metabolites undergo further metabolism into methyluric acids before being excreted in the urine. There is genetic variability in the metabolism of caffeine due to the polymorphism of CYP1A2. This variability can affect the pharmacokinetic and pharmacodynamic properties of caffeine and may affect an individual's consumption.
References
Caffeine Metabolism References
Kawajiri K, Gotoh O, Sogawa K, Tagashira Y, Muramatsu M, Fujii-Kuriyama Y: Coding nucleotide sequence of 3-methylcholanthrene-inducible cytochrome P-450d cDNA from rat liver. Proc Natl Acad Sci U S A. 1984 Mar;81(6):1649-53. doi: 10.1073/pnas.81.6.1649.
Pubmed: 6584898
Sogawa K, Gotoh O, Kawajiri K, Harada T, Fujii-Kuriyama Y: Complete nucleotide sequence of a methylcholanthrene-inducible cytochrome P-450 (P-450d) gene in the rat. J Biol Chem. 1985 Apr 25;260(8):5026-32.
Pubmed: 2985574
Wolfel C, Platt KL, Dogra S, Glatt H, Wachter F, Doehmer J: Stable expression of rat cytochrome P450IA2 cDNA and hydroxylation of 17 beta-estradiol and 2-aminofluorene in V79 Chinese hamster cells. Mol Carcinog. 1991;4(6):489-98.
Pubmed: 1793487
Song BJ, Gelboin HV, Park SS, Yang CS, Gonzalez FJ: Complementary DNA and protein sequences of ethanol-inducible rat and human cytochrome P-450s. Transcriptional and post-transcriptional regulation of the rat enzyme. J Biol Chem. 1986 Dec 15;261(35):16689-97.
Pubmed: 3782137
Umeno M, Song BJ, Kozak C, Gelboin HV, Gonzalez FJ: The rat P450IIE1 gene: complete intron and exon sequence, chromosome mapping, and correlation of developmental expression with specific 5' cytosine demethylation. J Biol Chem. 1988 Apr 5;263(10):4956-62.
Pubmed: 2832413
Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. doi: 10.1101/gr.2596504.
Pubmed: 15489334
Mahnke A, Strotkamp D, Roos PH, Hanstein WG, Chabot GG, Nef P: Expression and inducibility of cytochrome P450 3A9 (CYP3A9) and other members of the CYP3A subfamily in rat liver. Arch Biochem Biophys. 1997 Jan 1;337(1):62-8. doi: 10.1006/abbi.1996.9752.
Pubmed: 8990268
Wang H, Kawashima H, Strobel HW: cDNA cloning of a novel CYP3A from rat brain. Biochem Biophys Res Commun. 1996 Apr 5;221(1):157-62. doi: 10.1006/bbrc.1996.0562.
Pubmed: 8660328
Yoshioka H, Morohashi K, Sogawa K, Miyata T, Kawajiri K, Hirose T, Inayama S, Fujii-Kuriyama Y, Omura T: Structural analysis and specific expression of microsomal cytochrome P-450(M-1) mRNA in male rat livers. J Biol Chem. 1987 Feb 5;262(4):1706-11.
Pubmed: 3805049
Morishima N, Yoshioka H, Higashi Y, Sogawa K, Fujii-Kuriyama Y: Gene structure of cytochrome P-450(M-1) specifically expressed in male rat liver. Biochemistry. 1987 Dec 15;26(25):8279-85. doi: 10.1021/bi00399a039.
Pubmed: 2894840
Strom A, Mode A, Zaphiropoulos P, Nilsson AG, Morgan E, Gustafsson JA: Cloning and pretranslational hormonal regulation of testosterone 16 alpha-hydroxylase (P-45016 alpha) in male rat liver. Acta Endocrinol (Copenh). 1988 Jun;118(2):314-20. doi: 10.1530/acta.0.1180314.
Pubmed: 2455430
This pathway was propagated using PathWhiz -
Pon, A. et al. Pathways with PathWhiz (2015) Nucleic Acids Res. 43(Web Server issue): W552–W559.
Propagated from SMP0000028
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