Regulation of the Arachidonic Acid Cascade and PAF Metabolism in Reproductive Tissues
Murray D. Mitchell in Eicosanoids in Reproduction, 2020
Glycerophospholipid degradation in mammalian tissue is primarily catalyzed by the action of phospholipases, as illustrated in Figure 2. With the exception of phosphatidylinositol, most glycerophospholipids are degraded via phospholipase A enzymes. The phosphatidylinositol pathway employs phospholipase C; the products of this reaction are inositol phosphate(s) and diacylglycerol. The role of the inositol polyphosphates and diacylglycerol as second messengers and the relationship of Ca2+ to signal transduction and protein kinase C activity have recently been reviewed.31,32 More recently, a role for phospholipase D, which has been purified from mammalian tissues,33 has been implicated in the generation of phosphatidic acid, which may subsequently function as a second messenger.34
Phosphoinositide Metabolism
Enrique Pimentel in Handbook of Growth Factors, 2017
Phosphatidylinositol and its phosphorylated derivatives, which include mono- and polyphosphates, represent less than 6 to 8% of the components of the membranes of eukaryotic cells. However, they are important components of cell membranes and are crucially involved in receptor-mediated activation of intracellular signaling mechanisms. Various enzymes are involved in the regulation of phospholipid biosynthesis in eukaryotic cells,21 as well as in the phosphorylation and hydrolysis of cellular phospholipids.22 The hydrolytic enzymes involved in such processes include several phospholipases. The phosphorylation of phosphatidylinositol depends on the activity of phosphatidylinositol kinases with different substrate specificities. While the generation of phosphatidylinositol 4-monophosphate depends on the activity of phosphatidylinositol kinase type II, the type I enzyme is involved in the generation of phosphatidylinositol 3-monophosphate.23 Further phosphorylation of the monophosphate gives origin to phosphatidylinositol 4,5-bisphosphate, a compound that has been found to be involved in the activation of a low affinity form of human DNA polymerase-α, suggesting that it may function as a second messenger during the initiation of mitosis.24
Cell Structure and Functions
Malgorzata Lekka in Cellular Analysis by Atomic Force Microscopy, 2017
Phosphoglycerides are derivatives of glycerol-3-phosphate. They have two hydrocarbon chains in the glycerol backbone and one phosphoric acid (or one phosphoric acid esterified group). The main members of phosphoglycerides are phosphatic acid (PA), phosphatidylocholine (PC), phosphatidyl-ethanolamine (PE), phosphatidylserine (PS, Fig. 2.7b), and phosphatidylinositol (PI). Hydrophilic regions of phospholipid molecules contain acidic phosphate groups possessing a negative charge (at pH 7.0). The other component of the hydrophilic region may be serine, choline, ethanolamine, or inositol. Both choline and ethanolamine contain the positively charged amino groups. The presence of two oppositely charged groups in the polar head of a lipid gives it the character of a dipolar ion with no net charge. Phospholipids containing serine or inositol have a negative net charge. Sphingolipids are derivatives of sphingosine, which is a long unsaturated alcohol chain. The most abundant, representative molecule is a sphingomyelin residing mostly in nerve cells but also present in kidney tissue and blood. This molecule contains very little amount of unsaturated fatty acids attached with sphingosine through nitrogen atom.
Dual role of quercetin in enhancing the efficacy of cisplatin in chemotherapy and protection against its side effects: a review
Published in Archives of Physiology and Biochemistry, 2022
Masoud Najafi, Shima Tavakol, Ali Zarrabi, Milad Ashrafizadeh
Ovarian cancer (OC) is one of the most malignant tumours among women and claims the eighth place among other cancers in females (Angeli et al.2020). Currently, there is no cure for effective eradication of OC and because of its high incidence rate, it is considered as one of the major public health issues (Mahalaxmi et al.2019). Chemotherapy and radiotherapy are common non-invasive and minimal invasive strategies in OC therapy (Revaux et al.2020). Notably, the resistance of OC cells has significantly reduced the efficacy of chemotherapy. The co-administration of quercetin and CP has more inhibitory impact on the growth and proliferation of OC cells compared to CP alone (Scambia et al. 1990). It is said that dose-dependent cytotoxicity of quercetin sensitises OC cells into CP chemotherapy (Scambia et al.1990). The capability of quercetin in induction of cell cycle arrest at G1 and S phases exerts anti-proliferative activity in OC cells. This effect on the proliferation is mediated through suppressing phosphatidylinositol conversion into IP3 via down-regulation of 1-phosphatidylinositol 4-kinase (Shen and Weber 1997).
Clinical development of an anti-GPC-1 antibody for the treatment of cancer
Published in Expert Opinion on Biological Therapy, 2022
Saikat Ghosh, Pie Huda, Nicholas Fletcher, Douglas Campbell, Kristofer J. Thurecht, Bradley Walsh
Proteoglycans are composed of glycosylated proteins with covalently attached glycosaminoglycan (GAG) chains [1]. In 1990, David et al. reported their seminal investigation of a novel membrane-associated proteoglycan present in human lung fibroblasts [2]. The cDNA of the proteoglycan was cloned and sequenced by the research group and the core protein was found to contain short hydrophobic amino acid sequences at its C-terminus without a proper cytoplasmic domain. Both these features were reminiscent of membrane-bound phosphatidylinositol-anchored proteins. At the time, the process of phospholipid anchoring through an enzyme-catalyzed transamidation reaction was known as glypiation. This led to proposal of the name ‘Glypican’ by David et al. for the newly discovered ‘glypiated proteoglycan.’
Cholecalciferol ameliorates insulin signalling and insulin regulation of enzymes involved in glucose metabolism in the rat heart
Published in Archives of Physiology and Biochemistry, 2021
Tamara Ivkovic, Tijana Culafic, Snezana Tepavcevic, Snjezana Romic, Mojca Stojiljkovic, Milan Kostic, Jelena Stanisic, Goran Koricanac
Abel (Abel 2021) recently presented in detail the cardiac insulin signalling pathway. Insulin binds to plasma membrane receptor (IR) that phosphorylates itself and insulin receptor substrates (IRS). Insulin accomplishes its metabolic effects by activating the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) pathway. Akt is a serine/threonine kinase that phosphorylates numerous targets of different functions. Transcription factor Forkhead box protein O1 (FOXO1) is one of them. FOXO1 phosphorylation by Akt leads to its extrusion from the nucleus and downregulation of transcriptional activity (Riehle and Abel 2016). mTOR complex 1 is also regulated by insulin via Akt activity. Its activation leads to the intensification of protein synthesis (through p70 S6K1 kinase) and inhibition of autophagia (Yoon 2017). However, mTOR complex 1 hyperactivity leads to insulin signal attenuation (Yoon 2017). Specifically, S6K1, a substrate of mTOR complex 1, was found to phosphorylate IRS-1 at Ser307in vitro (Harrington et al. 2004). In addition, stimulation of another branch of insulin signalling leads to activation of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) pathway responsible for mitogenic effects of insulin.
Related Knowledge Centers
- Fatty Acid
- Glycerophospholipid
- Ph
- Phosphate
- Phosphorylation
- Cell Membrane
- Inositol
- Ph
- Muco-Inositol
- Phosphatidylinositol 4-Phosphate
- Phosphatidylinositol 4,5-Bisphosphate