SMPDB

Pathway Description

Adefovir Dipivoxil Metabolism Pathway

Homo sapiens

Drug Metabolism Pathway

Created: 2013-09-11

Last Updated: 2025-01-24

Adefovir dipivoxil is an ester prodrug of adefovir, a nucleotide analogue used in the treatment of chronic hepatitis B. Adefovir dipivoxil is taken up into the liver cell and is cleaved into adefovir by intracellular esterases. Adefovir is subsequently phosphorylated first by adenylate kinases and then by nucleoside diphosphate kinases into adefovir diphosphate. Adefovir diphosphate is an analogue of deoxyadenosine triphosphate (dATP) and competes with dATP for binding to the viral DNA polymerase and subsequent incorporation into the growing DNA strand. Once incorporated into the DNA, adefovir causes chain termination, thus preventing viral replication.

References

Adefovir Dipivoxil Pathway References

Dando T, Plosker G: Adefovir dipivoxil: a review of its use in chronic hepatitis B. Drugs. 2003;63(20):2215-34.

Pubmed: 14498759

Hepsera. (2009). e-CPS (online version of Compendium of Pharmaceuticals and Specialties). Retrieved December 16, 2009.

Von Zabern I, Wittmann-Liebold B, Untucht-Grau R, Schirmer RH, Pai EF: Primary and tertiary structure of the principal human adenylate kinase. Eur J Biochem. 1976 Sep;68(1):281-90. doi: 10.1111/j.1432-1033.1976.tb10787.x.

Pubmed: 183954

Matsuura S, Igarashi M, Tanizawa Y, Yamada M, Kishi F, Kajii T, Fujii H, Miwa S, Sakurai M, Nakazawa A: Human adenylate kinase deficiency associated with hemolytic anemia. A single base substitution affecting solubility and catalytic activity of the cytosolic adenylate kinase. J Biol Chem. 1989 Jun 15;264(17):10148-55.

Pubmed: 2542324

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

Lee Y, Kim JW, Lee IA, Kang HB, Choe YK, Lee HG, Lim JS, Kim HJ, Park C, Choe IS: Cloning and characterization of cDNA for human adenylate kinase 2A. Biochem Mol Biol Int. 1996 Jul;39(4):833-42.

Pubmed: 8843353

Lee Y, Kim JW, Lee SM, Kim HJ, Lee KS, Park C, Choe IS: Cloning and expression of human adenylate kinase 2 isozymes: differential expression of adenylate kinase 1 and 2 in human muscle tissues. J Biochem. 1998 Jan;123(1):47-54. doi: 10.1093/oxfordjournals.jbchem.a021915.

Pubmed: 9504408

Noma T, Song S, Yoon YS, Tanaka S, Nakazawa A: cDNA cloning and tissue-specific expression of the gene encoding human adenylate kinase isozyme 2. Biochim Biophys Acta. 1998 Jan 7;1395(1):34-9. doi: 10.1016/s0167-4781(97)00193-0.

Pubmed: 9434148

Rosengard AM, Krutzsch HC, Shearn A, Biggs JR, Barker E, Margulies IM, King CR, Liotta LA, Steeg PS: Reduced Nm23/Awd protein in tumour metastasis and aberrant Drosophila development. Nature. 1989 Nov 9;342(6246):177-80. doi: 10.1038/342177a0.

Pubmed: 2509941

Gilles AM, Presecan E, Vonica A, Lascu I: Nucleoside diphosphate kinase from human erythrocytes. Structural characterization of the two polypeptide chains responsible for heterogeneity of the hexameric enzyme. J Biol Chem. 1991 May 15;266(14):8784-9.

Pubmed: 1851158

Wang L, Patel U, Ghosh L, Chen HC, Banerjee S: Mutation in the nm23 gene is associated with metastasis in colorectal cancer. Cancer Res. 1993 Feb 15;53(4):717-20.

Pubmed: 7916650

Stahl JA, Leone A, Rosengard AM, Porter L, King CR, Steeg PS: Identification of a second human nm23 gene, nm23-H2. Cancer Res. 1991 Jan 1;51(1):445-9.

Pubmed: 1988104

Postel EH, Berberich SJ, Flint SJ, Ferrone CA: Human c-myc transcription factor PuF identified as nm23-H2 nucleoside diphosphate kinase, a candidate suppressor of tumor metastasis. Science. 1993 Jul 23;261(5120):478-80. doi: 10.1126/science.8392752.

Pubmed: 8392752

Highlighted elements will appear in red.

Highlight Compounds

	Adefovir
	Adefovir Diphosphate
	Adefovir Dipivoxil
	Adefovir Monophosphate
	Magnesium

Highlight Proteins

	Adenylate kinase 2, mitochondrial
	Adenylate kinase isoenzyme 1
	Nucleoside diphosphate kinase A
	Nucleoside diphosphate kinase B

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