PathWhiz

PathWhiz ID	Pathway	Meta Data
PW000051 View Pathway	metabolic Valine, Leucine, and Isoleucine Degradation Homo sapiens Valine, isoleuciine, and leucine are essential amino acids and are identified as the branched-chain amino acids (BCAAs). The catabolism of all three amino acids starts in muscle and yields NADH and FADH2 which can be utilized for ATP generation. The catabolism of all three of these amino acids uses the same enzymes in the first two steps. The first step in each case is a transamination using a single BCAA aminotransferase, with α-ketoglutarate as the amine acceptor. As a result, three different α-keto acids are produced and are oxidized using a common branched-chain α-keto acid dehydrogenase (BCKD), yielding the three different CoA derivatives. Isovaleryl-CoA is produced from leucine by these two reactions, alpha-methylbutyryl-CoA from isoleucine, and isobutyryl-CoA from valine. These acyl-CoA’s undergo dehydrogenation, catalyzed by three different but related enzymes, and the breakdown pathways then diverge. Leucine is ultimately converted into acetyl-CoA and acetoacetate; isoleucine into acetyl-CoA and succinyl-CoA; and valine into propionyl-CoA (and subsequently succinyl-CoA). Under fasting conditions, substantial amounts of all three amino acids are generated by protein breakdown. In muscle, the final products of leucine, isoleucine, and valine catabolism can be fully oxidized via the citric acid cycle; in the liver, they can be directed toward the synthesis of ketone bodies (acetoacetate and acetyl-CoA) and glucose (succinyl-CoA). Because isoleucine catabolism terminates with the production of acetyl-CoA and propionyl-CoA, it is both glucogenic and ketogenic. Because leucine gives rise to acetyl-CoA and acetoacetyl-CoA, it is classified as strictly ketogenic. BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: WishartLab Created On: August 01, 2013 at 13:54 Last Updated: August 01, 2013 at 13:54
PW064779 View Pathway	metabolic Valine,leucine,isoleucine degradation Homo sapiens BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Carin Li Created On: June 25, 2018 at 14:08 Last Updated: June 25, 2018 at 14:08
PW132221 View Pathway	metabolic Valproate bismuth Drug Metabolism Homo sapiens Valproate bismuth is a drug that is not metabolized by the human body as determined by current research and biotransformer analysis. Valproate bismuth passes through the liver and is then excreted from the body mainly through the kidney. BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Ray Kruger Created On: September 21, 2023 at 20:14 Last Updated: September 21, 2023 at 20:14
PW146698 View Pathway	drug action Valproate bismuth Drug Metabolism Action Pathway Homo sapiens BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Ray Kruger Created On: October 07, 2023 at 18:49 Last Updated: October 07, 2023 at 18:49
PW124228 View Pathway	drug action Valproate w/ Template (New) Drug Action Action Pathway Homo sapiens BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Nitya Khetarpal Created On: October 15, 2020 at 21:45 Last Updated: October 15, 2020 at 21:45
PW124164 View Pathway	drug action Valproic Acid (Drug Action) - New - DISCARD Homo sapiens BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Nitya Khetarpal Created On: September 16, 2020 at 08:07 Last Updated: September 16, 2020 at 08:07
PW144440 View Pathway	drug action Valproic acid Drug Metabolism Action Pathway Homo sapiens BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Ray Kruger Created On: October 07, 2023 at 13:38 Last Updated: October 07, 2023 at 13:38
PW124475 View Pathway	drug action Valproic Acid i.e. Sodium Valproate (New: Drug Action) Homo sapiens Sodium valproate, also known as valproic acid, is a fatty acid derivative and anticonvulsant first synthesized in 1881-1882 from an analogue derived from the Valerian herb; however, its mechanism of action is not fully elucidated (yet). Traditionally, researchers and clinicians consider it to be an anticonvulsant due to its effects in the brain: it blocks voltage-gated sodium channels and potentiates gamma-aminobutyric acid (GABA) activity. Over the past centuries, investigations show valproate may also have neuroprotective, anti-manic, and anti-migraine effects. It is a compound of interest in the field of oncology for its anti-proliferative effects and has undergone some clinical trials. Currently, valproate is indicated for use as a monotherapy or adjunct medication in seizure management, for migraine prophylaxis, and for mitigation of acute mania associated with bipolar disorder. Off-label, clinicians may use valproate to manage bipolar disorder or for emergency treatment of status epilepticus. Valproate can be administered orally, in which case it undergoes hepatic first-pass metabolism to enter the bloodstream ___________________ https://go.drugbank.com/drugs/DB00313 BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Nitya Khetarpal Created On: January 24, 2021 at 01:14 Last Updated: January 24, 2021 at 01:14
PW000611 View Pathway	drug metabolism Valproic Acid Metabolism Pathway Homo sapiens Valproic acid (VPA) is metabolized almost entirely in the liver, via at least there routes: glucuronidation, beta oxidation in the mitochondria, and cytochrome P450 mediated oxidation. The glucuronidation of VPA is mediated by UGT1A3, UGT1A4, UGT1A6, UGT1A8, UGT1A9, UGT1A10, UGT2B7 and UGT2B15. The key CYP-mediated reaction of the VPA metabolic pathway is the generation of 4-ene-VPA by CYP2C9, CYP2A6 and CYP2B6. These three enzymes also catalyze the formation of 4-OH-VPA and 5-OH-VPA. Moreover, CYP2A6 mediates the oxidation of VPA to 3-OH-VPA. Inside the mitochondria, the first step of oxidation is the formation of (VPA-CoA) catalyzed by medium-chain acyl-CoA synthase, followed by the conversion to 2-ene-VPA-CoA through 2-methyl-branched chain acyl-CoA dehydrogenase (ACADSB). 2-ene-VPA-CoA is further converted to 3-hydroxyl-valproyl-VPA (3-OH-VPA-CoA) by an enoyl-CoA hydratase, crotonase (ECSH1) and then 3-OH-VPA-CoA is metabolized to 3-keto-valproyl-CoA (3-oxo-VPA-CoA) through the action of 2-methyl-3-hydroxybutyryl-CoA dehydrogenase. Another route of VPA metabolism in the mitochondria includes the conversion of 4-ene-VPA to 4-ene-VPA-CoA ester catalyzed by ACADSB, followed by a beta-oxidation to form 2,4-diene-VPA-CoA ester. The latter metabolite can furthermore be conjugated to glutathione to form thiol metabolites. BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: WishartLab Created On: September 11, 2013 at 22:33 Last Updated: September 11, 2013 at 22:33
PW127712 View Pathway	drug action Valrubicin Action Pathway Homo sapiens Valrubicin (N-trifluoroacetyladriamycin-14-valerate), also known as Valstar, is a chemotherapy drug from the anthracycline class. It is a semisynthetic analog of doxorubicin. Valrubicin has a more rapid uptake in the tumors than doxorubicin. Moreover, it does not have the preferential negative ion binding in cell membranes thought to be the cause for the cardiac toxicity of doxorubicin. This drug is used to treat BCG-resistant bladder carcinoma and is administered directly in the bladder (intravesical). Valrubicin affects a variety of interrelated biological functions, mostly the one involving the nucleic acid metabolism. It does DNA intercalation, then, it inhibits the incorporation of nucleosides into nucleic acids, causes extensive chromosomal damage, and arrests the cell cycle in the G2 phase. A principal mechanism of its action, mediated by valrubicin metabolites, is interference with the normal DNA breaking-resealing action of DNA topoisomerase II. This drug inhibits the DNA topoisomerase by binding to its 2-alpha part. This action cause DNA strand breaks, partial unwinding/uncoiling of DNA, and inhibition of DNA and RNA synthesis. DNA damage leads to programmed cell death (apoptosis) of the cancer cells, preventing the growth and proliferation of cancer in patients. BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Daphnee Created On: May 25, 2023 at 09:20 Last Updated: May 25, 2023 at 09:20