Genes altered in major depressive disorder
Genes altered in major depressive disorder
Positive relationships between GSTM4 and other components at different levels (count: 0)
Positive relationship network of GSTM4 in MK4MDD
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Note:
1. The different color of the nodes denotes the level of the nodes.
Genetic/Epigenetic Locus
Protein and Other Molecule
Cell and Molecular Pathway
Neural System
Cognition and Behavior
Symptoms and Signs
Environment
MDD
2. Besides the component related relationships from literature, gene mapped protein and protein mapped gene are also shown in the network.
If the mapped gene or protein is not from literature, square node would be used instead of Circle node.
Accordingly, the relationship is marked with dot line.
2. User can drag the nodes to rearrange the layout of the network. Click the node will enter the report page of the node.
Right-click will show also the menus to link to the report page of the node and remove the node and related edges.
Hover the node will show the level of the node and hover the edge will show the evidence/description of the edge.
3. The network is generated using Cytoscape Web
Negative relationships between GSTM4 and MDD (count: 0)
Negative relationships between GSTM4 and other components at different levels (count: 0)
Phase II of biotransformation is concerned with conjugation,......
Phase II of biotransformation is concerned with conjugation, that is using groups from cofactors to react with functional groups present or introduced from phase I on the compound. The enzymes involved are a set of transferases which perform the transfer of the cofactor group to the substrate. The resultant conjugation results in greatly increasing the excretory potential of compounds. Although most conjugations result in pharmacological inactivation or detoxification, some can result in bioactivation. Most of the phase II enzymes are located in the cytosol except UDP-glucuronosyltransferases (UGT), which are microsomal. Phase II reactions are typically much faster than phase I reactions therefore the rate-limiting step for biotransformation of a compound is usually the phase I reaction. Phase II metabolism can deal with all the products of phase I metabolism, be they reactive (Type I substrate) or unreactive/poorly active (Type II substrate) compounds. With the exception of glutathione, the conjugating species needs to be made chemically reactive after synthesis. The availability of the cofactor in the synthesis may be a rate-limiting factor in some phase II pathways as it may prevent the formation of enough conjugating species to deal with the substrate or it's metabolite. As many substrates and/or their metabolites are chemically reactive, their continued presence may lead to toxicity.More...
Glutathione S-Transferases (GSTs; EC 2.5.1.18) are another m......
Glutathione S-Transferases (GSTs; EC 2.5.1.18) are another major set of phase II conjugation enzymes. They can be found in the cytosol as well as being microsomal membrane-bound. Cytosolic GSTs are encoded by at least 5 gene families (alpha, mu, pi, theta and zeta GST) whereas membrane-bound enzymes are encoded by single genes. Soluble GSTs are homo- or hetero-dimeric enzymes (approximately 25KDa subunits) which can act on a wide range of endogenous and exogenous electrophiles. GSTs mediate conjugation using glutathione (GSH), a tripeptide synthesized from its precursor amino acids gamma-glutamate, cysteine and glycine. A generalized reaction is RX + GSH -> HX + GSR Glutathione conjugates are excreted in bile and converted to cysteine and mercapturic acid conjugates in the intestine and kidneys. GSH is the major, low molecular weight, non-protein thiol synthesized de novo in mammalian cells. As well as taking part in conjugation reactions, GSH also has antioxidant ability and can metabolize endogenous and exogenous compounds. The nucleophilic GSH attacks the electrophilic substrate forming a thioether bond between the cysteine residue of GSH and the electrophile. The result is generally a less reactive and more water-soluble conjugate that can be easily excreted. In some cases, GSTs can activate compounds to reactive species such as certain haloalkanes and haloalkenes. Substrates for GSTs include epoxides, alkenes and compounds with electrophilic carbon, sulfur or nitrogen centres. There are two types of conjugation reaction with glutathione: displacement reactions where glutathione displaces an electron-withdrawing group and addition reactions where glutathione is added to activated double bond structures or strained ring systems.More...
All organisms are constantly exposed to foreign chemicals ev......
All organisms are constantly exposed to foreign chemicals every day. These can be man-made. Once chemicals undergo functionalization, the electrophilic or nucleophilic species can be detrimental to biological systems. Electrophiles can react with electron-rich macromolecules such as proteins, DNA and RNA by covalent interaction whilst nucleophiles have the potential to interact with biological receptors. That's why conjugation is so important as it mops up these potentially reactive species. Many chemicals, when exposed to certain metabolizing enzymes can induce those enzymes, a process called enzyme induction. The effect of this is that these chemicals accelerate their own biotransformation and excretion. The reverse is also true where some chemicals cause enzyme inhibition. Some other factors that alter enzyme levels are sex, age and genetic predisposition. Between species, there can be considerable differences in biotransformation ability which is a problem faced by drug researchers interpreting toxicological results to humans.More...
GSTM4 related interactors from protein-protein interaction data in HPRD (count: 10)