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Pathways

PathWhiz ID Pathway Meta Data

PW146083

Pw146083 View Pathway
drug action

Thallous chloride Drug Metabolism Action Pathway

Homo sapiens

PW146963

Pw146963 View Pathway
drug action

Thallous chloride Tl-201 Drug Metabolism Action Pathway

Homo sapiens

PW124119

Pw124119 View Pathway
signaling

THC on CB1

Homo sapiens
The main psychoactive component in cannabis, △9-tetrahydrocannabinol (THC), acts on CB1 receptors in the brain located on synaptic terminals. THC, whose 3D structure closely resembles that of the endogenous cannabinoid anandamide, acts as a partial agonist on these receptors. Several behavioural effects of cannabis are feelings of euphoria, relaxation, lack of concentration,and altered time perception, while physiological effects range from increased appetite to rapid changes in heart rate. The mechanism of action of THC works through the activation CB1, which inhibits adenylate cyclase and lowers levels of cyclic AMP in the cell. This further inhibits protein kinase A complex, which affects regulating synaptic membrane exocytosis protein through an as yet unknown mechanism. This regulating protein is responsible for the release of GABA or ɣ-aminobutyric acid by exocytosis from the inhibitory terminal of the neuron. GABA is normally released to inhibit and regulate the release of dopamine in the brain. The binding of THC limits the exocytosis of GABA, and so dopamine is able to travel along synapses and bind to receptors. This promotes the well-known euphoric effects of cannabis. The activated CB1 receptor also interacts with its normal physiological targets, activating both MAPK and potassium channels and inhibiting calcium channels. These interactions and their physiological downstream effects are responsible for the numerous side effects associated with cannabis such as lack of concentration and impaired learning. The sustained effects of THC can be explained by the ability of CB1 receptors to influence long term plasticity in the brain.

PW000987

Pw000987 View Pathway
metabolic

The Citric Acid Cycle Tutorial

Homo sapiens

PW000983

Pw000983 View Pathway
metabolic

The Citric Acid Cycle Tutorial (2) - Pt.3 Adding Labels

Homo sapiens

PW000986

Pw000986 View Pathway
metabolic

The Citric Acid Cycle Tutorial (2) - Pt.4 Adding SubPathways

Homo sapiens

PW000973

Pw000973 View Pathway
metabolic

The Citric Acid Cycle Tutorial (2) Pt.1 - Adding Reactions

Homo sapiens

PW000982

Pw000982 View Pathway
metabolic

The Citric Acid Cycle Tutorial (2) Pt.2 - Adding Membranes

Homo sapiens

PW122260

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.

PW002359

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.