PathWhiz

PathWhiz ID	Pathway	Meta Data
PW127426 View Pathway	drug action Artenimol Action Pathway Homo sapiens Artenimol is an artemisinin derivative and antimalarial agent used in the treatment of uncomplicated Plasmodium falciparum infections. It is used in combination with Piperaquine. Artemisinins, including Artenimol which is a major active metabolite of many artemisinins, are believed to bind to haem within the P. falciparum parasite. The source of this haem varies with the life stage of the parasite. When the parasite is in the early ring stage artemisinins are believed to bind haem produced by the parasite's haem biosynthesis pathway. In later stages artemisinins likely bind to haem released by haemoglobin digestion. Once bound to haem, artemisinins are thought to undergo activation involving ferrous iron via reductive scission which splits the endoperoxide bridge to produce a reactive oxygen. This reactive oxygen is thought to undergo a subsequent intramolecular hydrogen abstraction to produce a reactive carbon radical. The carbon radical is believed to be the source of the drugs potent activity against P. falciparum by alkylating a wide array of protein targets. The nature and magnitude of the effect on specific protein function as a result of this alkylation is unknown. One target which has been the focus of research is the sarco/endoplasmic reticulum Ca2+ ATPase pump of P. falciparum. Artemisinins have been found to irreversably bind to and inhibit this protein at a binding site similar to that of Thapsigargin. BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Ray Kruger Created On: January 29, 2023 at 15:09 Last Updated: January 29, 2023 at 15:09
PW146684 View Pathway	drug action Artemotil Drug Metabolism Action Pathway Homo sapiens BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Ray Kruger Created On: October 07, 2023 at 18:47 Last Updated: October 07, 2023 at 18:47
PW132456 View Pathway	metabolic Artemotil Drug Metabolism Homo sapiens Artemotil is a drug that is not metabolized by the human body as determined by current research and biotransformer analysis. Artemotil 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 21:53 Last Updated: September 21, 2023 at 21:53
PW000627 View Pathway	drug metabolism Artemether Metabolism Pathway Homo sapiens Artemether is a semisynthetic derivative of artemisinin, a phytoconstituent that acts as a short-acting antimalarial agent and is used to treat uncomplicated Plasmodium falciparum malaria. Artemisinin derivatives kill parasites more rapidly than conventional antimalarial drugs, and are active against both the sexual and asexual stages of the parasite cycle. However due to their short half-life (and to prevent resistance development) artemisinin compounds are often combined with long-acting antimalarial drugs. Artemeter is administered orally and as an oil-based intramuscular injection. The antimalarial activity of artemether and other artemisinin derivatives is a result of the peroxide bridge found in the active metabolite dihydroartemisinin. Dihydroartemisinin is formed from the rapid demethylation of artmether via CYP3A4 and CYP3A5. It then undergoes glucuronidation catalyzed by the UDP-glucuronosyltransferases UGT1A9 and UGT2B7 into inactive metabolites that are eliminated in the bile. BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: WishartLab Created On: September 18, 2013 at 09:42 Last Updated: September 18, 2013 at 09:42
PW145738 View Pathway	drug action Artemether Drug Metabolism Action Pathway Homo sapiens BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Ray Kruger Created On: October 07, 2023 at 16:31 Last Updated: October 07, 2023 at 16:31
PW126885 View Pathway	drug action Artemether Action Pathway (New) Homo sapiens Artemether is used to treat malaria usually in combination with lumefantrine in order to achieve greater efficacy in treatment. Artemether can be taken in a tablet or intramuscular injection, once administered into the body it has a rapid onset and is metabolized into an active metabolite dihydroartemisinin (DHA). DHA then enters the malaria cell and into the vacuole where it interacts with heme (a byproduct of hemoglobin) and creating cytotoxic radical species. This hinders growth and halts parasitic growth by damaging the food vacuole. This eventually causes cell death. Food can be taken to help increase absorption, although grapefruit products should be avoided as they inhibit CYP450 3A4. If CYP450 3A4 is inhibited this reduces the clearance of artemether, leading to excessive plasma concentrations of artemether which can cause cardiovascular complications. DHA is then broken down by glucuronosyltransferases through glucuronidation so that it can become an inactive metabolite that is then excreted through bile. BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Selena Created On: April 29, 2022 at 00:19 Last Updated: April 29, 2022 at 00:19
PW145256 View Pathway	drug action Arsenic trioxide Drug Metabolism Action Pathway Homo sapiens BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Ray Kruger Created On: October 07, 2023 at 15:25 Last Updated: October 07, 2023 at 15:25
PW122396 View Pathway	metabolic Arsenate Detoxification Homo sapiens Arsenate is a compound similar to phosphate, but containing an arsenic atom instead of the phosphorous. As such, it is treated similarly to a phosphate ion. However, if the arsenate replaces inorganic phosphates in glycolysis, it allows glycolysis to proceed, but does not generate ATP, uncoupling glycolysis. It can also bind to lipoic acid in the Krebs cycle, leading to a greater loss of ATP. Arsenate can enter into the cell via aquaporins 7 and 9, as well as facilitated glucose transporter members 1 and 4 of solute carrier family 2, and does so by diffusion. Once inside the cell, the arsenate can be converted to arsenite via the glutathione S-transferase omega-1 enzyme, or it can be converted to ribose-1-arsenate via the purine nucleoside phosphorylase. Ribose-1-arsenate then can spontaneously form arsenite through a reaction involving hydrogen and dihydrolipoate. After arsenite has been formed by either of these methods, arsenite methyltransferase catalyzes its formation into methylarsonate. From here, it forms methylarsonite via the glutathione S-transferase omega-1 enzyme again. The methylarsonite reacts with S-adenosylmethionine, catalyzed by arsenite methyltransferase, in order to become dimethylarsinate. Finally, the compound once again interacts with the glutathione S-transferase omega-1 enzyme to form dimethylarsinous acid, the final compound in this pathway. BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Eponine Oler Created On: March 20, 2019 at 12:51 Last Updated: March 20, 2019 at 12:51
PW121708 View Pathway	disease Aromatic L-Aminoacid Decarboxylase Deficiency Mus musculus Aromatic L-Aminoacid Decarboxylase Deficiency (DOPA decarboxylase; DDC) is an autosomal recessive disease caused by a mutation in the DDC gene which codes for aromatic-L-aminoacid decarboxylase. A deficiency in this enzyme results in accumulation of 3-methoxytyrosine, 5-hydroxy-L-tryptophan, and L-Dopa in plasma, spinal fluid, and urine; 3-methoxytyramine and dopamine in urine. It also results in decreased concentrations of homovanillic acid, S-adenosylmethionine, and 5-hydroxytryptophol in spinal fluid; and epinephrine, norepinephrine in plasma. Symptoms include temperature instability, hypotonia, mental and motor retardation, and cerebral atrophy. BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Ana Marcu Created On: September 10, 2018 at 15:49 Last Updated: September 10, 2018 at 15:49
PW127174 View Pathway	disease Aromatic L-Aminoacid Decarboxylase Deficiency Homo sapiens Aromatic L-Aminoacid Decarboxylase Deficiency (DOPA decarboxylase; DDC) is an autosomal recessive disease caused by a mutation in the DDC gene which codes for aromatic-L-aminoacid decarboxylase. A deficiency in this enzyme results in accumulation of 3-methoxytyrosine, 5-hydroxy-L-tryptophan, and L-Dopa in plasma, spinal fluid, and urine; 3-methoxytyramine and dopamine in urine. It also results in decreased concentrations of homovanillic acid, S-adenosylmethionine, and 5-hydroxytryptophol in spinal fluid; and epinephrine, norepinephrine in plasma. Symptoms include temperature instability, hypotonia, mental and motor retardation, and cerebral atrophy. BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Ray Kruger Created On: November 02, 2022 at 09:23 Last Updated: November 02, 2022 at 09:23