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Phosphatidylinositol Transfer Protein, Membrane-associated 2
Phosphatidylinositol (or Inositol Phospholipid) consists of a family of lipids as illustrated on the right, where red is x, blue is y, and black is z, in the context of independent variation, a class of the phosphatidylglycerides. In such molecules the isomer of the inositol group is assumed to be the myo- conformer unless otherwise stated. Typically phosphatidylinositols form a minor component on the cytosolic side of eukaryotic cell membranes. The phosphate group gives the molecules a negative charge at physiological pH. The form of phosphatidylinositol comprising the isomer ''muco''-inositol acts as a sensory receptor in the taste function of the sensory system. In this context it is often referred to as PtdIns, but that does not imply any molecular difference from phosphatidylinositols comprising the myo- conformers of inositol. The phosphatidylinositol can be phosphorylated to form phosphatidylinositol phosphate (PI-4-P, referred to as PIP in close context or inform ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Glycerophospholipid
Glycerophospholipids or phosphoglycerides are glycerol-based phospholipids. They are the main component of biological membranes. Two major classes are known: those for bacteria and eukaryotes and a separate family for archaea. Structures The term glycerophospholipid signifies any derivative of glycerophosphoric acid that contains at least one ''O''-acyl, or ''O''-alkyl, or ''O''-alk-1'-enyl residue attached to the glycerol moiety. The phosphate group forms an ester linkage to the glycerol. The long-chained hydrocarbons are typically attached through ester linkages in bacteria/eucaryotes and by ether linkages in archaea. In bacteria and procaryotes, the lipids consist of diesters commonly of C16 or C18 fatty acids. These acids are straight-chained and, especially for the C18 members, can be unsaturated. For archaea, the hydrocarbon chains have chain lengths of C10, C15, C20 etc. since they are derived from isoprene units. These chains are branched, with one methyl substitue ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Lipid Signaling
Lipid signaling, broadly defined, refers to any biological signaling event involving a lipid messenger that binds a protein target, such as a receptor, kinase or phosphatase, which in turn mediate the effects of these lipids on specific cellular responses. Lipid signaling is thought to be qualitatively different from other classical signaling paradigms (such as monoamine neurotransmission) because lipids can freely diffuse through membranes (''see osmosis''). One consequence of this is that lipid messengers cannot be stored in vesicles prior to release and so are often biosynthesized "on demand" at their intended site of action. As such, many lipid signaling molecules cannot circulate freely in solution but, rather, exist bound to special carrier proteins in serum. Sphingolipid second messengers Ceramide Ceramide (Cer) can be generated by the breakdown of sphingomyelin (SM) by sphingomyelinases (SMases), which are enzymes that hydrolyze the phosphocholine group from the sph ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Inositol Phosphate
Inositol phosphates are a group of mono- to hexaphosphorylated inositols. They play crucial roles in diverse cellular functions, such as cell growth, apoptosis, cell migration, endocytosis, and cell differentiation. The group comprises: * inositol monophosphate (IP) * inositol bisphosphate (IP2) * inositol trisphosphate (IP3) * inositol pentakisphosphate (IP5) * inositol hexaphosphate (IP6) also known as phytic acid, or phytate (as a salt). Functions Inositol triphosphate Inositol trisphosphates act on the inositol triphosphate receptor to release calcium into the cytoplasm. ''Further reading: Function of calcium in humans'' Other Inositol tetra-, penta-, and hexa-phosphates have been implicated in gene expression Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, protein or non-coding RNA, and ultimately affect a phenotype, as the final effect. The .... Inositol hexa ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
PI 3-kinase
Phosphoinositide 3-kinases (PI3Ks), also called phosphatidylinositol 3-kinases, are a family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, which in turn are involved in cancer. PI3Ks are a family of related intracellular signal transducer enzymes capable of phosphorylating the 3 position hydroxyl group of the inositol ring of phosphatidylinositol (PtdIns). The pathway, with oncogene PIK3CA and tumor suppressor gene PTEN, is implicated in the sensitivity of cancer tumors to insulin and IGF1, and in calorie restriction. Discovery The discovery of PI3Ks by Lewis Cantley and colleagues began with their identification of a previously unknown phosphoinositide kinase associated with the polyoma middle T protein. They observed unique substrate specificity and chromatographic properties of the products of the lipid kinase, leading to the discovery that this phosphoinositide kinase had ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Phosphatidylinositol 3,4,5-trisphosphate
Phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)''P''3), abbreviated PIP3, is the product of the class I phosphoinositide 3-kinases (PI 3-kinases) phosphorylation of phosphatidylinositol (4,5)-bisphosphate (PIP2). It is a phospholipid that resides on the plasma membrane. Discovery In 1988, Lewis C. Cantley published a paper describing the discovery of a novel type of phosphoinositide kinase with the unprecedented ability to phosphorylate the 3' position of the inositol ring resulting in the formation of phosphatidylinositol-3-phosphate (PI3P). Working independently, Alexis Traynor-Kaplan and coworkers published a paper demonstrating that a novel lipid, phosphatidylinositol 3,4,5 trisphosphate (PIP3) occurs naturally in human neutrophils with levels that increased rapidly following physiologic stimulation with chemotactic peptide. Subsequent studies demonstrated that ''in vivo'' the enzyme originally identified by Cantley's group prefers PtdIns(4,5)P2 as a substrate, pro ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Phosphatidylinositol 4,5-bisphosphate
Phosphatidylinositol 4,5-bisphosphate or PtdIns(4,5)''P''2, also known simply as PIP2 or PI(4,5)P2, is a minor phospholipid component of cell membranes. PtdIns(4,5)''P''2 is enriched at the plasma membrane where it is a substrate for a number of important signaling proteins. PIP2 also forms lipid clusters that sort proteins. PIP2 is formed primarily by the type I phosphatidylinositol 4-phosphate 5-kinases from PI(4)P. In metazoans, PIP2 can also be formed by type II phosphatidylinositol 5-phosphate 4-kinases from PI(5)P. The fatty acids of PIP2 are variable in different species and tissues, but the most common fatty acids are stearic in position 1 and arachidonic in 2. Signaling pathways PIP2 is a part of many cellular signaling pathways, including PIP2 cycle, PI3K signalling, and PI5P metabolism. Recently, it has been found in the nucleus with unknown function. Functions Cytoskeleton dynamics near membranes PIP2 regulates the organization, polymerization, and bran ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Phosphatidylinositol 3,5-bisphosphate
Phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) is one of the seven phosphoinositides found in eukaryotic cell membranes. In quiescent cells, the PtdIns(3,5)P2 levels, typically quantified by HPLC, are the lowest amongst the constitutively present phosphoinositides. They are approximately 3 to 5-fold lower as compared to PtdIns3P and PtdIns5P ( Phosphatidylinositol 5-phosphate) levels, and more than 100-fold lower than the abundant PtdIns4P ( Phosphatidylinositol 4-phosphate) and PtdIns(4,5)P2. PtdIns(3,5)P2 was first reported to occur in mouse fibroblasts and budding yeast S. cerevisiae in 1997.Whiteford CC, Brearley CA, Ulug ET. Phosphatidylinositol 3,5-bisphosphate defines a novel PI 3-kinase pathway in resting mouse fibroblasts. Biochem J. 1997 May 1;323 ( Pt 3):597-601. In S. cerevisiae PtdIns(3,5)P2 levels increase dramatically during hyperosmotic shock.Dove SK, Cooke FT, Douglas MR, Sayers LG, Parker PJ, Michell RH. Osmotic stress activates phosphatidylinositol-3,5-b ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Phosphatidylinositol 3,4-bisphosphate
Phosphatidylinositol (3,4)-bisphosphate (PtdIns(3,4)''P''2) is a minor phospholipid component of cell membranes, yet an important second messenger. The generation of PtdIns(3,4)''P''2 at the plasma membrane activates a number of important cell signaling pathways. Of all the phospholipids found within the membrane, inositol phospholipids make up less than 10%. Phosphoinositide’s (PI’s) also known as phosphatidylinositol phosphates, are synthesized in the cells endoplasmic reticulum by the protein phosphatidylinositol synthase (PIS). PI’s are highly compartmentalized, their main components include a glycerol backbone, two fatty acid chains enriched with stearic acid and arachidonic acid, and an inositol ring whose phosphate groups regulation differs between organelles depending on the specific PI and PIP kinases and PIP phosphatases present in the organelle (Image 1). These kinases and phosphatases conduct phosphorylation and dephosphorylation at the inositol sugar head groups ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Phosphatidylinositol 5-phosphate
Phosphatidylinositol 5-phosphate (PtdIns5P) is a phosphoinositide, one of the phosphorylated derivatives of phosphatidylinositol (PtdIns), that are well-established membrane-anchored regulatory molecules. Phosphoinositides participate in signaling events that control cytoskeletal dynamics, intracellular membrane trafficking, cell proliferation and many other cellular functions. Generally, phosphoinositides transduce signals by recruiting specific phosphoinositide-binding proteins to intracellular membranes. Phosphatidylinositol 5-phosphate is one of the 7 known cellular phosphoinositides with less understood functions. It is phosphorylated on position D-5 of the inositol head group, which is attached via phosphodiester linkage to diacylglycerol (with varying chemical composition of the acyl chains, frequently 1-stearoyl-2-arachidonoyl chain). In quiescent cells, on average, PtdIns5P is of similar or higher abundance as compared to PtdIns3P and ~20-100-fold below the levels of PtdIn ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Phosphatidylinositol 4-phosphate
Phosphatidylinositol-4-phosphate (PtdIns4''P'', PI-4-P, PI4P, or PIP) is a precursor of phosphatidylinositol (4,5)-bisphosphate. PtdIns4''P'' is prevalent in the membrane of the Golgi apparatus. In the Golgi apparatus, PtdIns4''P'' binds to the GTP-binding protein ARF and to effector proteins, including four-phosphate-adaptor protein 1 and 2 ( PLEKHA3 and PLEKHA8). This three molecule complex recruits proteins that need to be carried to the cell membrane. There is now evidence that PI-4-P is capable of deforming lipid systems into tightly curved assemblies, this is consistent with similar behaviour observed in phosphatidylinositol. See also * Phosphatidylinositol 3-phosphate Phosphatidylinositol 3-phosphate (PtdIns3''P'') is a phospholipid found in cell membranes that helps to recruit a range of proteins, many of which are involved in protein trafficking, to the membranes. It is the product of both the class II and ... * Phosphatidylinositol 5-phosphate * Phosphatidylinosi ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Phosphatidylinositol 3-phosphate
Phosphatidylinositol 3-phosphate (PtdIns3''P'') is a phospholipid found in cell membranes that helps to recruit a range of proteins, many of which are involved in protein trafficking, to the membranes. It is the product of both the class II and III phosphoinositide 3-kinases (PI 3-kinases) activity on phosphatidylinositol. PtdIns3''P'' is dephosphorylated by the myotubularin family of phosphatases, on the D3 position of the inositol ring, and can be converted to PtdIns(3,5)''P''2 by the lipid kinase PIKfyve. Both FYVE domains and PX domains – found in proteins such as SNX1, HGS, and EEA1 – bind to PtdIns3''P''. The majority of PtdIns3''P'' appears to be constitutively synthesised by the class III PI 3-kinase, PIK3C3 (Vps34), at endocytic membranes. Class II PI 3-kinases also appear to synthesise PtdIns3''P'', their activity however appears to be regulated by a range of stimuli, including growth factors. This suggests that specific pools of PtdIns3''P'' may be s ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Steric Hindrance
Steric effects arise from the spatial arrangement of atoms. When atoms come close together there is a rise in the energy of the molecule. Steric effects are nonbonding interactions that influence the shape ( conformation) and reactivity of ions and molecules. Steric effects complement electronic effects, which dictate the shape and reactivity of molecules. Steric repulsive forces between overlapping electron clouds result in structured groupings of molecules stabilized by the way that opposites attract and like charges repel. Steric hindrance Steric hindrance is a consequence of steric effects. Steric hindrance is the slowing of chemical reactions due to steric bulk. It is usually manifested in ''intermolecular reactions'', whereas discussion of steric effects often focus on ''intramolecular interactions''. Steric hindrance is often exploited to control selectivity, such as slowing unwanted side-reactions. Steric hindrance between adjacent groups can also affect torsional ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
