
Loading Pathway...
Error: Pathway image not found.
Hide
Pathway Description
Mycophenolic Acid Action Pathway
Homo sapiens
Drug Action Pathway
Created: 2020-08-07
Last Updated: 2023-10-25
Mycophenolic acid is an immunosuppressant drug and anti-proliferative drug derived from Penicillium stoloniferum. It inhibits the purine de novo synthesis for purine nucleotides through inhibiting the enzyme inosine 5'-monophosphate dehydrogenase which catalyzes the conversion of inosinic acid into xanthylic acid. This step in the purine de novo pathway is the first commited step towards guanosine/guanine synthesis and it's inhibition blocks all route to produce the nucleotide. Mycophenolic acid is a selective, reversible and potent inhibitor of the enzyme. Since T and B lymphocytes are reliant on the purine de novo synthesis pathway for proliferation, it's blockage has cytostatic effects. Other cells are able to obtain purines from other sources but T and B lymphocytes can only get it from the pathway. Inhibition stops DNA and RNA synthesis which suppress the ability for T and B cells to proliferate rapidly. Mycophenolic acid also suppresses antibody creation for B cells and glycosylation of the lymphocytes to glycoproteins on monocytes which is critical for intercellular adhesion to endothelial cells. It is also possible that mycophenolic acid inhibits leukocyte recruitment to inflammation and graft rejection sites. Mycophenolic acid is administered orally in the form of a delayed release tablet.
References
Mycophenolic Acid Pathway References
Tedesco-Silva H, Bastien MC, Choi L, Felipe C, Campestrini J, Picard F, Schmouder R: Mycophenolic acid metabolite profile in renal transplant patients receiving enteric-coated mycophenolate sodium or mycophenolate mofetil. Transplant Proc. 2005 Mar;37(2):852-5. doi: 10.1016/j.transproceed.2004.12.186.
Pubmed: 15848554
Bittersohl H, Steimer W. Chapter 9 - Intracellular concentrations of immunosuppressants. Personalized Immunosuppression in Transplantation, 199-226, 2016.
Dasgupta A, Chapter 4 - Monitoring free mycophenolic acid concentration: Is there any clinical advantage?, Personalized Immunosuppression in Transplantation, 83-107, 2016.
Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M: DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. doi: 10.1093/nar/gkx1037.
Pubmed: 29126136
Zha M, Guo Q, Zhang Y, Yu B, Ou Y, Zhong C, Ding J: Molecular mechanism of ADP-ribose hydrolysis by human NUDT5 from structural and kinetic studies. J Mol Biol. 2008 Jun 6;379(3):568-78. doi: 10.1016/j.jmb.2008.04.006. Epub 2008 Apr 8.
Pubmed: 18462755
Gasmi L, Cartwright JL, McLennan AG: Cloning, expression and characterization of YSA1H, a human adenosine 5'-diphosphosugar pyrophosphatase possessing a MutT motif. Biochem J. 1999 Dec 1;344 Pt 2:331-7.
Pubmed: 10567213
Yang H, Slupska MM, Wei YF, Tai JH, Luther WM, Xia YR, Shih DM, Chiang JH, Baikalov C, Fitz-Gibbon S, Phan IT, Conrad A, Miller JH: Cloning and characterization of a new member of the Nudix hydrolases from human and mouse. J Biol Chem. 2000 Mar 24;275(12):8844-53. doi: 10.1074/jbc.275.12.8844.
Pubmed: 10722730
Taira M, Iizasa T, Shimada H, Kudoh J, Shimizu N, Tatibana M: A human testis-specific mRNA for phosphoribosylpyrophosphate synthetase that initiates from a non-AUG codon. J Biol Chem. 1990 Sep 25;265(27):16491-7.
Pubmed: 2168892
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
Iwahana H, Oka J, Mizusawa N, Kudo E, Ii S, Yoshimoto K, Holmes EW, Itakura M: Molecular cloning of human amidophosphoribosyltransferase. Biochem Biophys Res Commun. 1993 Jan 15;190(1):192-200. doi: 10.1006/bbrc.1993.1030.
Pubmed: 8380692
Brayton KA, Chen Z, Zhou G, Nagy PL, Gavalas A, Trent JM, Deaven LL, Dixon JE, Zalkin H: Two genes for de novo purine nucleotide synthesis on human chromosome 4 are closely linked and divergently transcribed. J Biol Chem. 1994 Feb 18;269(7):5313-21.
Pubmed: 8106516
Aimi J, Qiu H, Williams J, Zalkin H, Dixon JE: De novo purine nucleotide biosynthesis: cloning of human and avian cDNAs encoding the trifunctional glycinamide ribonucleotide synthetase-aminoimidazole ribonucleotide synthetase-glycinamide ribonucleotide transformylase by functional complementation in E. coli. Nucleic Acids Res. 1990 Nov 25;18(22):6665-72. doi: 10.1093/nar/18.22.6665.
Pubmed: 2147474
Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. doi: 10.1038/ng1285. Epub 2003 Dec 21.
Pubmed: 14702039
Patterson D, Bleskan J, Gardiner K, Bowersox J: Human phosphoribosylformylglycineamide amidotransferase (FGARAT): regional mapping, complete coding sequence, isolation of a functional genomic clone, and DNA sequence analysis. Gene. 1999 Nov 1;239(2):381-91. doi: 10.1016/s0378-1119(99)00378-9.
Pubmed: 10548741
Nagase T, Ishikawa K, Nakajima D, Ohira M, Seki N, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O: Prediction of the coding sequences of unidentified human genes. VII. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro. DNA Res. 1997 Apr 28;4(2):141-50. doi: 10.1093/dnares/4.2.141.
Pubmed: 9205841
Zody MC, Garber M, Adams DJ, Sharpe T, Harrow J, Lupski JR, Nicholson C, Searle SM, Wilming L, Young SK, Abouelleil A, Allen NR, Bi W, Bloom T, Borowsky ML, Bugalter BE, Butler J, Chang JL, Chen CK, Cook A, Corum B, Cuomo CA, de Jong PJ, DeCaprio D, Dewar K, FitzGerald M, Gilbert J, Gibson R, Gnerre S, Goldstein S, Grafham DV, Grocock R, Hafez N, Hagopian DS, Hart E, Norman CH, Humphray S, Jaffe DB, Jones M, Kamal M, Khodiyar VK, LaButti K, Laird G, Lehoczky J, Liu X, Lokyitsang T, Loveland J, Lui A, Macdonald P, Major JE, Matthews L, Mauceli E, McCarroll SA, Mihalev AH, Mudge J, Nguyen C, Nicol R, O'Leary SB, Osoegawa K, Schwartz DC, Shaw-Smith C, Stankiewicz P, Steward C, Swarbreck D, Venkataraman V, Whittaker CA, Yang X, Zimmer AR, Bradley A, Hubbard T, Birren BW, Rogers J, Lander ES, Nusbaum C: DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage. Nature. 2006 Apr 20;440(7087):1045-9. doi: 10.1038/nature04689.
Pubmed: 16625196
Li SX, Tong YP, Xie XC, Wang QH, Zhou HN, Han Y, Zhang ZY, Gao W, Li SG, Zhang XC, Bi RC: Octameric structure of the human bifunctional enzyme PAICS in purine biosynthesis. J Mol Biol. 2007 Mar 9;366(5):1603-14. doi: 10.1016/j.jmb.2006.12.027. Epub 2006 Dec 16.
Pubmed: 17224163
Minet M, Lacroute F: Cloning and sequencing of a human cDNA coding for a multifunctional polypeptide of the purine pathway by complementation of the ade2-101 mutant in Saccharomyces cerevisiae. Curr Genet. 1990 Nov;18(4):287-91.
Pubmed: 2253271
Bechtel S, Rosenfelder H, Duda A, Schmidt CP, Ernst U, Wellenreuther R, Mehrle A, Schuster C, Bahr A, Blocker H, Heubner D, Hoerlein A, Michel G, Wedler H, Kohrer K, Ottenwalder B, Poustka A, Wiemann S, Schupp I: The full-ORF clone resource of the German cDNA Consortium. BMC Genomics. 2007 Oct 31;8:399. doi: 10.1186/1471-2164-8-399.
Pubmed: 17974005
Highlighted elements will appear in red.
Highlight Compounds
Highlight Proteins
Enter relative concentration values (without units). Elements will be highlighted in a color gradient where red = lowest concentration and green = highest concentration. For the best results, view the pathway in Black and White.
Visualize Compound Data
Visualize Protein Data
Downloads
Settings