PathWhiz

PathWhiz ID	Pathway	Meta Data
PW000973 View Pathway	metabolic The Citric Acid Cycle Tutorial (2) Pt.1 - Adding Reactions Homo sapiens BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Guest: Anonymous Created On: July 14, 2015 at 11:57 Last Updated: July 14, 2015 at 11:57
PW000982 View Pathway	metabolic The Citric Acid Cycle Tutorial (2) Pt.2 - Adding Membranes Homo sapiens BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Guest: Anonymous Created On: July 16, 2015 at 11:53 Last Updated: July 16, 2015 at 11:53
PW122260 View Pathway	metabolic The MEP/DOXP pathway of Paenibacillus Bacteria Terpenoids, also known as isoprenoids, are a large class of natural products consisting of isoprene (C5) units. There are two biosynthetic pathways, the mevalonate pathway [MD:M00095] and the non-mevalonate pathway or the MEP/DOXP pathway [MD:M00096], for the terpenoid building blocks: isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). The action of prenyltransferases then generates higher-order building blocks: geranyl diphosphate (GPP), farsenyl diphosphate (FPP), and geranylgeranyl diphosphate (GGPP), which are the precursors of monoterpenoids (C10), sesquiterpenoids (C15), and diterpenoids (C20), respectively. Condensation of these building blocks gives rise to the precursors of sterols (C30) and carotenoids (C40). The MEP/DOXP pathway is absent in higher animals and fungi, but in green plants the MEP/DOXP and mevalonate pathways co-exist in separate cellular compartments. The MEP/DOXP pathway, operating in the plastids, is responsible for the formation of essential oil monoterpenes and linalyl acetate, some sesquiterpenes, diterpenes, and carotenoids and phytol. The mevalonate pathway, operating in the cytosol, gives rise to triterpenes, sterols, and most sesquiterpenes. BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Ng Ngashangva Created On: October 18, 2018 at 02:56 Last Updated: October 18, 2018 at 02:56
PW002359 View Pathway	disease The Oncogenic Action of 2-Hydroxyglutarate Homo sapiens 2-Hydroxyglutarate is a compound formed from isocitric acid, a component of the TCA cycle. Isocitric acid becomes dehydrogenated by isocitrate dehydrogenase using NADP as a cofactor, and forming oxoglutaric acid. Oxoglutaric acid then forms 2-hydroxyglutarate in a reaction catalyzed by a mutant isocitrate dehydrogenase 2 enzyme, which also uses NADP as a cofactor. Normally, the isocitrate dehydrogenase 2 enzyme, encoded by the IDH2 gene, is responsible for the formation of 2-oxoglutaric acid from isocitrate. However, some gain-of-functions mutations to the IDH2 gene allow the enzyme to produce 2-hydroxyglutarate instead. This functionality is associated with several types of cancer, including glioma and acute myeloid leukemia. This is due to the buildup of 2-hydroxyglutarate, which inhibits several enzymes which rely on 2-oxoglutaric acid, such as methylcytosine dioxygenase and lysine-specific demethylase 2A. Both of these enzymes use 2-oxoglutarate to demethylate DNA, and when repressed, allow DNA to become hypermethylated. This in turn changes which genes are normally expressed, as methylation is used to suppress genes, and can lead to the expression of oncogenes or the repression of tumor-suppressing genes. This is the effect responsible for 2-hydroxyglutarate in cancer and other diseases. BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: miguel ramirez Created On: November 16, 2015 at 11:41 Last Updated: November 16, 2015 at 11:41
PW109800 View Pathway	disease The Oncogenic Action of 2-Hydroxyglutarate Mus musculus 2-Hydroxyglutarate is a compound formed from isocitric acid, a component of the TCA cycle. Isocitric acid becomes dehydrogenated by isocitrate dehydrogenase using NADP as a cofactor, and forming oxoglutaric acid. Oxoglutaric acid then forms 2-hydroxyglutarate in a reaction catalyzed by a mutant isocitrate dehydrogenase 2 enzyme, which also uses NADP as a cofactor. Normally, the isocitrate dehydrogenase 2 enzyme, encoded by the IDH2 gene, is responsible for the formation of 2-oxoglutaric acid from isocitrate. However, some gain-of-functions mutations to the IDH2 gene allow the enzyme to produce 2-hydroxyglutarate instead. This functionality is associated with several types of cancer, including glioma and acute myeloid leukemia. This is due to the buildup of 2-hydroxyglutarate, which inhibits several enzymes which rely on 2-oxoglutaric acid, such as methylcytosine dioxygenase and lysine-specific demethylase 2A. Both of these enzymes use 2-oxoglutarate to demethylate DNA, and when repressed, allow DNA to become hypermethylated. This in turn changes which genes are normally expressed, as methylation is used to suppress genes, and can lead to the expression of oncogenes or the repression of tumor-suppressing genes. This is the effect responsible for 2-hydroxyglutarate in cancer and other diseases. BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Ana Marcu Created On: August 31, 2018 at 15:50 Last Updated: August 31, 2018 at 15:50
PW109814 View Pathway	disease The Oncogenic Action of 2-Hydroxyglutarate Rattus norvegicus 2-Hydroxyglutarate is a compound formed from isocitric acid, a component of the TCA cycle. Isocitric acid becomes dehydrogenated by isocitrate dehydrogenase using NADP as a cofactor, and forming oxoglutaric acid. Oxoglutaric acid then forms 2-hydroxyglutarate in a reaction catalyzed by a mutant isocitrate dehydrogenase 2 enzyme, which also uses NADP as a cofactor. Normally, the isocitrate dehydrogenase 2 enzyme, encoded by the IDH2 gene, is responsible for the formation of 2-oxoglutaric acid from isocitrate. However, some gain-of-functions mutations to the IDH2 gene allow the enzyme to produce 2-hydroxyglutarate instead. This functionality is associated with several types of cancer, including glioma and acute myeloid leukemia. This is due to the buildup of 2-hydroxyglutarate, which inhibits several enzymes which rely on 2-oxoglutaric acid, such as methylcytosine dioxygenase and lysine-specific demethylase 2A. Both of these enzymes use 2-oxoglutarate to demethylate DNA, and when repressed, allow DNA to become hypermethylated. This in turn changes which genes are normally expressed, as methylation is used to suppress genes, and can lead to the expression of oncogenes or the repression of tumor-suppressing genes. This is the effect responsible for 2-hydroxyglutarate in cancer and other diseases. BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Ana Marcu Created On: August 31, 2018 at 15:53 Last Updated: August 31, 2018 at 15:53
PW002452 View Pathway	disease The Oncogenic Action of D-2-Hydroxyglutarate in Hydroxyglutaric aciduria Homo sapiens Hydroxyglutaric aciduria is a rare genetic disorder. Both isoforms are believed to have autosomal recessive inheritance. The compound 2-hydroxyglutarate is the product of gain-of-function mutations producing mutIDH1 and mutIDH2 in the cytosolic and mitochondrial isoforms of isocitrate dehydrogenase (IDH). This compound is derived from the TCA cycle. The compound 2-hydroxyglutarate shares structural similarity with 2-oxogluratate (2OG) to inhibit a range of 2OG-dependent dioxygenases, including histone lysine demethylases (KDMs) and the ten-eleven translocation (TET) family of 5-methylcytosine (5mC) hydroxylases. This results in modulations of HIF-mediated hypoxia responses and alterations in gene expression through global epigenetic remodelling that may contribute to malignant transformation. 2-Hydroxyglutarate dehydrogenase (D2HGDH) converts D-2-hydroxyglutarate (D-2HG) to α-ketoglutaric acid. The enzyme D-3-phosphoglycerate dehydrogenase (PHGDH) catalyzes the NADH-dependent reduction of α-ketoglutarate (AKG) to D-2HG. D-2-Hydroxyglutarate is an oncometabolite produced from IDH mutations. A mutation in IDH causes high concentrations of D-2-Hydroxyglutaric acid. D-2-hydroxyglutarate is a competitive inhibitor of 2OG-dependent dioxygenases resulting in genetic changes and malignancies. BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: miguel ramirez Created On: February 10, 2016 at 15:57 Last Updated: February 10, 2016 at 15:57
PW002363 View Pathway	disease The Oncogenic Action of Fumarate Homo sapiens Hypoxia-inducible factor In many tumours, oxygen availability becomes limited (hypoxia) very quickly during cancer development. The major regulator of the response to hypoxia is the HIF transcription factor. Under normal oxygen levels, the protein levels of HIF alpa is very low due to constant degradation, mediated by a sequence of post-translational modification events catalyzed by the enzymes PHD1,2 and 3, (also known as EglN2,1 and 3). Under hypoxic conditions, HIF alpha escapes hydroxylation and degration. Fumarate hydratase (FH) is a housekeeping gene, but mutations in this gene allows for fumarate to accumulate and cross the mitochondrial barrier through a dicarboxylate carrier. Once in the cytosol, it inhibits the activity of the PHD1,2 and 3 since it is chemically similar to succinate. Having a double bond in the centre of the dicarboxylic acid, fumarate is a rigid molecule compared to succinate making it a probable possibility for fumarate to interacts better with PHDs. BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: miguel ramirez Created On: November 19, 2015 at 09:58 Last Updated: November 19, 2015 at 09:58
PW002451 View Pathway	disease The Oncogenic Action of L-2-Hydroxyglutarate in Hydroxyglutaric aciduria Homo sapiens Hydroxyglutaric aciduria is a rare genetic disorder. Both isoforms are believed to have autosomal recessive inheritance. The compound 2-hydroxyglutarate is the product of gain-of-function mutations producing mutIDH1 and mutIDH2 in the cytosolic and mitochondrial isoforms of isocitrate dehydrogenase (IDH). This compound is derived from the TCA cycle. The compound 2-hydroxyglutarate shares enough structural similarity to 2-oxogluratate (2OG) to inhibit a range of 2OG-dependent dioxygenases, including histone lysine demethylases (KDMs) and the ten-eleven translocation (TET) family of 5-methylcytosine (5mC) hydroxylases. This results in modulations of HIF-mediated hypoxia responses and alterations in gene expression through global epigenetic remodelling that may contribute to malignant transformation. L-2-hydroxyglutarate dehydrogenase (L2HGDH) converts L-2-hydroxyglutarate to α-ketoglutaric acid. L-2-Hydroxyglutarate is an oncometabolite and is produced by gain-of-function IDH mutations. When IDH is mutated, L-2-Hydroxyglutaric acid production is increased. L-2-hydroxyglutarate is a competitive inhibitor of 2OG-dependent dioxygenases resulting in genetic changes and malignancies. BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: miguel ramirez Created On: February 10, 2016 at 13:13 Last Updated: February 10, 2016 at 13:13
PW002508 View Pathway	disease The oncogenic action of Serine: serine, one carbon cycle glycine synthesis (SOG) Homo sapiens The SOG pathway is depicted as the combination of serine, one-carbon cycle and glycine cleavage all acting together in tumour cells. Glycolysis is upregulated in tumour cells, thus serine is synthesized from 3-phosphoglycerate whichis then coverted to glycine bya cytosolic serine hydroxymethyltransferase. Serine and glycine can also be transported into the mitochondria. Serine can be converted to glycine in the mitochondria where glycine can be incorporated into the glycine cleavage cycle. The serine reaction that yields glycine also produces 5,10-Methylene-THF which is incorporated into the one-carbon cycle. L-serine in mitochodria reacts with THF leading to the mitochondrial ne carbon cycle and the production of NADPH used in the transport of hydrogen ions into the mitochondria. ATP synthase is used to transport hydrogen outside of the mitochondria, generating ATP in the process. The SOG pathway is predicted to be mainly active in tumour cells with decreased activity from the pyruvate kinase protein. BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: miguel ramirez Created On: March 23, 2016 at 13:44 Last Updated: March 23, 2016 at 13:44