Biological Pathway: Reactome:R-HSA-9680350
Signaling by CSF1 (M-CSF) in myeloid cells related metabolites
find 8 related metabolites which is associated with the biological pathway Signaling by CSF1 (M-CSF) in myeloid cells
this pathway object is a organism specific pathway, which is related to taxonomy Homo sapiens (human).
Colony stimulating factor-1 (CSF1, CSF-1, also called macrophage colony stimulating factor, M-CSF) is a disulfide-linked dimer that stimulates the proliferation and differentiation of mononuclear phagocytes and the survival, proliferation, motility, and anti-inflammatory activity of macrophages (reviewed in Mouchemore et al. 2012, Stanley and Chitu 2014, Ushach and Zlotnik 2016, Dwyer et al. 2017 and inferred from mouse homologs in Caescu et al. 2015). The unliganded CSF1 receptor, CSF1R (CSF-1R) is either clustered or undergoing rapid dimer-monomer transitions at the cell surface (Li and Stanley 1991). The CSF1 dimer initially binds the D2 and D3 extracellular domains of a monomer of CSF1R (Wang et al. 1993, Chihara et al. 2010, Ma et al. 2012, Felix et al. 2015, and inferred from mouse homologs). A second monomer of CSF1R then binds the CSF1:CSF1R complex and the resulting dimerization of CSF1R activates its kinase activity (Elegheert et al. 2011, Felix et al. 2015, and inferred from mouse homologs). CSF1R initially trans-autophosphorylates tyrosine-561 in the juxtamembrane domain, relieving negative autoinhibition of kinase activity, resulting in the trans-autophosphorylation of 7 more tyrosine residues in its cytoplasmic domain (Rohrschneider et al. 1997, Chihara et al. 2010, and inferred from mouse homologs in Xiong et al. 2011).
The PIK3R1 (p85alpha) regulatory subunit of phosphatidylinositol 3-kinase (PI3K) binds phosphotyrosine-723 of CSF1R, phosphorylated SRC binds phosphotyrosine-561 of CSF1R, phosphorylated CBL binds CSF1R associated with SHC, and GRB2:SOS binds CSF1R (Saleem et al. 1995, and inferred from mouse homologs). The resulting activation of the catalytic subunit of PI3K (PIK2CA,B,G) produces phosphatidylinositol 3,4,5-trisphosphate which recruits effectors containing pleckstrin homology domains (PH domains) such as PKB (also called Akt) to the plasma membrane. Pathways activated by PI3K appear to both enhance proliferation, survival, and migration of macrophages (reviewed in Dwyer et al. 2017) and, via induction of miR21, suppress the inflammatory response by targeting mRNAs encoding multiple proinflammatory molecules.
Phospholipase C gamma2 (PLCG2) binds phosphotyrosine-723 of CSF1R, hydrolyzes phosphatidylcholine to yield choline phosphate (phosphocholine) and diacylglycerol, and promotes survival and differentiation of macrophages via PKCdelta (PRKCD) (inferred from mouse homologs).
GRB2 bound to SOS1 (GRB2:SOS1) transiently interacts with phosphotyrosine-699 of CSF1R. SOS1 promotes the exchange of GDP for GTP by KRAS, activating the RAS-RAF-ERK1,2 pathway that causes proliferation of macrophage precursors (inferred from mouse homologs). CBL transiently associates with and ubiquitinates the CSF1R, then is deubiquitinated and returned to the cytoplasm (inferred from mouse homologs).
Phosphorylated CSF1R also recruits STAT1 and STAT3, which are then phosphorylated (inferred from mouse homologs). The role of phosphorylated STAT1,3 in signaling by CSF1R is incompletely characterized.
CSF1R is a target for therapeutics, such as imatinib (reviewed in Kumari et al. 2018).
Choline phosphate
Phosphorylcholine, also known as choline phosphate or N-trimethyl-2-aminoethylphosphonate, is a member of the class of compounds known as phosphocholines. Phosphocholines are compounds containing a [2-(trimethylazaniumyl)ethoxy]phosphonic acid or derivative. Phosphorylcholine is slightly soluble (in water) and a moderately acidic compound (based on its pKa). Phosphorylcholine can be found in a number of food items such as grapefruit, lime, black cabbage, and barley, which makes phosphorylcholine a potential biomarker for the consumption of these food products. Phosphorylcholine can be found primarily in most biofluids, including urine, blood, saliva, and cerebrospinal fluid (CSF), as well as throughout most human tissues. Phosphorylcholine exists in all eukaryotes, ranging from yeast to humans. In humans, phosphorylcholine is involved in several metabolic pathways, some of which include phosphatidylcholine biosynthesis PC(13D5/9D5), phosphatidylcholine biosynthesis PC(22:5(4Z,7Z,10Z,13Z,16Z)/22:5(7Z,10Z,13Z,16Z,19Z)), phosphatidylcholine biosynthesis PC(14:0/20:1(11Z)), and phosphatidylcholine biosynthesis PC(11D5/9D5). Phosphorylcholine is also involved in few metabolic disorders, which include fabry disease, gaucher disease, and krabbe disease. Moreover, phosphorylcholine is found to be associated with alzheimers disease and multi-infarct dementia. Phosphorylcholine (abbreviated ChoP) is the hydrophilic polar head group of some phospholipids, which is composed of a negatively charged phosphate bonded to a small, positively charged choline group. Phosphorylcholine is part of platelet-activating factor; the phospholipid phosphatidylcholine as well as sphingomyelin, the only phospholipid of the membrane that is not built with a glycerol backbone. Treatment of cell membranes, like those of RBCs, by certain enzymes, like some phospholipase A2 renders the phosphorylcholine moiety exposed to the external aqueous phase, and thus accessible for recognition by the immune system. Antibodies against phosphorylcholine are naturally occurring autoantibodies that are created by CD5+/B-1 B cells and are referred to as non-pathogenic autoantibodies . Phosphorylcholine, also known as choline phosphate or CHOP, belongs to the class of organic compounds known as phosphocholines. Phosphocholines are compounds containing a [2-(trimethylazaniumyl)ethoxy]phosphonic acid or derivative. The phosphate of choline, and the parent compound of the phosphorylcholine family. Phosphorylcholine exists in all living species, ranging from bacteria to humans. Within humans, phosphorylcholine participates in a number of enzymatic reactions. In particular, phosphorylcholine can be converted into choline through its interaction with the enzyme phosphoethanolamine/phosphocholine phosphatase. In addition, phosphorylcholine can be converted into CDP-choline; which is mediated by the enzyme choline-phosphate cytidylyltransferase a. In humans, phosphorylcholine is involved in phospholipid biosynthesis. Outside of the human body, phosphorylcholine has been detected, but not quantified in several different foods, such as barley, pak choy, black radish, saskatoon berries, and acorns. Acquisition and generation of the data is financially supported in part by CREST/JST. KEIO_ID P074
Water
Water is a chemical substance that is essential to all known forms of life. It appears colorless to the naked eye in small quantities, though it is actually slightly blue in color. It covers 71\\% of Earths surface. Current estimates suggest that there are 1.4 billion cubic kilometers (330 million m3) of it available on Earth, and it exists in many forms. It appears mostly in the oceans (saltwater) and polar ice caps, but it is also present as clouds, rain water, rivers, freshwater aquifers, lakes, and sea ice. Water in these bodies perpetually moves through a cycle of evaporation, precipitation, and runoff to the sea. Clean water is essential to human life. In many parts of the world, it is in short supply. From a biological standpoint, water has many distinct properties that are critical for the proliferation of life that set it apart from other substances. It carries out this role by allowing organic compounds to react in ways that ultimately allow replication. All known forms of life depend on water. Water is vital both as a solvent in which many of the bodys solutes dissolve and as an essential part of many metabolic processes within the body. Metabolism is the sum total of anabolism and catabolism. In anabolism, water is removed from molecules (through energy requiring enzymatic chemical reactions) in order to grow larger molecules (e.g. starches, triglycerides and proteins for storage of fuels and information). In catabolism, water is used to break bonds in order to generate smaller molecules (e.g. glucose, fatty acids and amino acids to be used for fuels for energy use or other purposes). Water is thus essential and central to these metabolic processes. Water is also central to photosynthesis and respiration. Photosynthetic cells use the suns energy to split off waters hydrogen from oxygen. Hydrogen is combined with CO2 (absorbed from air or water) to form glucose and release oxygen. All living cells use such fuels and oxidize the hydrogen and carbon to capture the suns energy and reform water and CO2 in the process (cellular respiration). Water is also central to acid-base neutrality and enzyme function. An acid, a hydrogen ion (H+, that is, a proton) donor, can be neutralized by a base, a proton acceptor such as hydroxide ion (OH-) to form water. Water is considered to be neutral, with a pH (the negative log of the hydrogen ion concentration) of 7. Acids have pH values less than 7 while bases have values greater than 7. Stomach acid (HCl) is useful to digestion. However, its corrosive effect on the esophagus during reflux can temporarily be neutralized by ingestion of a base such as aluminum hydroxide to produce the neutral molecules water and the salt aluminum chloride. Human biochemistry that involves enzymes usually performs optimally around a biologically neutral pH of 7.4. (Wikipedia). Water, also known as purified water or dihydrogen oxide, is a member of the class of compounds known as homogeneous other non-metal compounds. Homogeneous other non-metal compounds are inorganic non-metallic compounds in which the largest atom belongs to the class of other nonmetals. Water can be found in a number of food items such as caraway, oxheart cabbage, alaska wild rhubarb, and japanese walnut, which makes water a potential biomarker for the consumption of these food products. Water can be found primarily in most biofluids, including ascites Fluid, blood, cerebrospinal fluid (CSF), and lymph, as well as throughout all human tissues. Water exists in all living species, ranging from bacteria to humans. In humans, water is involved in several metabolic pathways, some of which include cardiolipin biosynthesis CL(20:4(5Z,8Z,11Z,14Z)/18:0/20:4(5Z,8Z,11Z,14Z)/18:2(9Z,12Z)), cardiolipin biosynthesis cl(i-13:0/i-15:0/i-20:0/i-24:0), cardiolipin biosynthesis CL(18:0/18:0/20:4(5Z,8Z,11Z,14Z)/22:5(7Z,10Z,13Z,16Z,19Z)), and cardiolipin biosynthesis cl(a-13:0/i-18:0/i-13:0/i-19:0). Water is also involved in several metabolic disorders, some of which include de novo triacylglycerol biosynthesis tg(i-21:0/i-13:0/21:0), de novo triacylglycerol biosynthesis tg(22:0/20:0/i-20:0), de novo triacylglycerol biosynthesis tg(a-21:0/i-20:0/i-14:0), and de novo triacylglycerol biosynthesis tg(i-21:0/a-17:0/i-12:0). Water is a drug which is used for diluting or dissolving drugs for intravenous, intramuscular or subcutaneous injection, according to instructions of the manufacturer of the drug to be administered [fda label]. Water plays an important role in the world economy. Approximately 70\\% of the freshwater used by humans goes to agriculture. Fishing in salt and fresh water bodies is a major source of food for many parts of the world. Much of long-distance trade of commodities (such as oil and natural gas) and manufactured products is transported by boats through seas, rivers, lakes, and canals. Large quantities of water, ice, and steam are used for cooling and heating, in industry and homes. Water is an excellent solvent for a wide variety of chemical substances; as such it is widely used in industrial processes, and in cooking and washing. Water is also central to many sports and other forms of entertainment, such as swimming, pleasure boating, boat racing, surfing, sport fishing, and diving .
H2O
An oxygen hydride consisting of an oxygen atom that is covalently bonded to two hydrogen atoms. Water. CAS Common Chemistry. CAS, a division of the American Chemical Society, n.d. https://commonchemistry.cas.org/detail?cas_rn=7732-18-5 (retrieved 2024-10-17) (CAS RN: 7732-18-5). Licensed under the Attribution-Noncommercial 4.0 International License (CC BY-NC 4.0).
Phosphocholine
C5H15NO4P+ (184.07386599999998)
The phosphate of choline; and the parent compound of the phosphocholine family.
[[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-oxidophosphoryl]oxy-oxidophosphoryl] phosphate
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Adenosine-diphosphate
COVID info from COVID-19 Disease Map, WikiPathways Corona-virus Coronavirus SARS-CoV-2 COVID-19 SARS-CoV COVID19 SARS2 SARS