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Pathway Description
Valacyclovir Action Pathway
Homo sapiens
Category:
Metabolite Pathway
Sub-Category:
Drug Action
Created: 2023-02-28
Last Updated: 2023-10-25
Valaciclovir (valacyclovir), also known as the brand name Valtrex, is an guanine nucleoside antiviral used to treat herpes exacerbations. Valaciclovir is the L-valine ester of aciclovir. Valacyclovir is rapidly and almost completely converted in man to aciclovir and valine, likely by the enzyme valacyclovir hydrolase. Aciclovir is transported from the liver into the blood via a drug transporter, then into the effected cells.
Acyclovir is a guanosine analog used to treat herpes simplex, varicella zoster, herpes zoster, herpes labialis, and acute herpetic keratitis. Acyclovir is becomes acyclovir monophosphate due to the action of viral thymidine kinase.5 Acyclovir monophosphate is converted to the diphosphate form by guanylate kinase.1 Acyclovir diphosphate is converted to acyclovir triphosphate by nucleoside diphosphate kinase, pyruvate kinase, creatine kinase, phosphoglycerate kinase, succinyl-CoA synthetase, phosphoenolpyruvate carboxykinase and adenylosuccinate synthetase. Acyclovir triphosphate inhibits the activity of DNA polymerase by competing with its substrate dGTP. Acyclovir triphosphate also gets incorporated into viral DNA, but since it lacks the 3'-OH group which is needed to form the 5′ to 3′ phosphodiester linkage essential for DNA chain elongation, this causes DNA chain termination, preventing the growth of viral DNA. Less Viral DNA is transported into the nucleus, therefore, less viral DNA is integrated into the host DNA. Less viral proteins produced, fewer viruses can form.
References
Valacyclovir Pathway References
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Pubmed: 6549046
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Fitzgibbon J, Katsanis N, Wells D, Delhanty J, Vallins W, Hunt DM: Human guanylate kinase (GUK1): cDNA sequence, expression and chromosomal localisation. FEBS Lett. 1996 May 6;385(3):185-8. doi: 10.1016/0014-5793(96)00365-1.
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Brady WA, Kokoris MS, Fitzgibbon M, Black ME: Cloning, characterization, and modeling of mouse and human guanylate kinases. J Biol Chem. 1996 Jul 12;271(28):16734-40. doi: 10.1074/jbc.271.28.16734.
Pubmed: 8663313
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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.
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Pubmed: 7916650
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Pubmed: 15644426
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Pubmed: 10049739
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