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IUBMB Life Jun 2010The glycerophospholipids phosphatidylcholine (PC) and phosphatidylethanolamine (PE) account for greater than 50% of the total phospholipid species in eukaryotic... (Review)
Review
The glycerophospholipids phosphatidylcholine (PC) and phosphatidylethanolamine (PE) account for greater than 50% of the total phospholipid species in eukaryotic membranes and thus play major roles in the structure and function of those membranes. In most eukaryotic cells, PC and PE are synthesized by an aminoalcoholphosphotransferase reaction, which uses sn-1,2-diradylglycerol and either CDP-choline or CDP-ethanolamine, respectively. This is the last step in a biosynthetic pathway known as the Kennedy pathway, so named after Eugene Kennedy who elucidated it over 50 years ago. This review will cover various aspects of the Kennedy pathway including: each of the biosynthetic steps, the functions and roles of the phospholipid products PC and PE, and how the Kennedy pathway has the potential of being a chemotherapeutic target against cancer and various infectious diseases.
Topics: Amino Acid Sequence; Animals; Humans; Molecular Sequence Data; Phosphatidylcholines; Phosphatidylethanolamines; Sequence Alignment; Signal Transduction
PubMed: 20503434
DOI: 10.1002/iub.337 -
Molecules (Basel, Switzerland) Jul 2023Phosphatidylcholine-specific phospholipase C (PC-PLC) is an enzyme that catalyzes the formation of the important secondary messengers phosphocholine and diacylglycerol... (Review)
Review
Phosphatidylcholine-specific phospholipase C (PC-PLC) is an enzyme that catalyzes the formation of the important secondary messengers phosphocholine and diacylglycerol (DAG) from phosphatidylcholine. Although PC-PLC has been linked to the progression of many pathological conditions, including cancer, atherosclerosis, inflammation and neuronal cell death, studies of PC-PLC on the protein level have been somewhat neglected with relatively scarce data. To date, the human gene expressing PC-PLC has not yet been found, and the only protein structure of PC-PLC that has been solved was from (PC-PLC). Nonetheless, there is evidence for PC-PLC activity as a human functional equivalent of its prokaryotic counterpart. Additionally, inhibitors of PC-PLC have been developed as potential therapeutic agents. The most notable classes include 2-aminohydroxamic acids, xanthates, ,'-hydroxyureas, phospholipid analogues, 1,4-oxazepines, pyrido[3,4-]indoles, morpholinobenzoic acids and univalent ions. However, many medicinal chemistry studies lack evidence for their cellular and in vivo effects, which hampers the progression of the inhibitors towards the clinic. This review outlines the pathological implications of PC-PLC and highlights current progress and future challenges in the development of PC-PLC inhibitors from the literature.
Topics: Humans; Type C Phospholipases; Phosphatidylcholines
PubMed: 37570610
DOI: 10.3390/molecules28155637 -
Molecular Membrane Biology 2015Since its discovery in the 19th century, phosphatidylcholine (PC) has been regarded primarily as a structural lipid. However, more recent evidence, much of it in the... (Review)
Review
Since its discovery in the 19th century, phosphatidylcholine (PC) has been regarded primarily as a structural lipid. However, more recent evidence, much of it in the last five years, strongly suggests that PC has other roles. Here, we explore some of that new evidence and consider the possibility that the ultimate role of phosphatidylcholine may not be predictable.
Topics: Animals; Cell Membrane; Gene Expression Regulation; Humans; Phosphatidylcholines; Protein Binding; Signal Transduction
PubMed: 26306852
DOI: 10.3109/09687688.2015.1066894 -
The Journal of Organic Chemistry Jun 2022Lysophosphatidylcholine (LPC) and phosphatidylcholine (PC) are important membrane constituents implicated in signaling and immune regulation. Synthesis of LPCs is...
Lysophosphatidylcholine (LPC) and phosphatidylcholine (PC) are important membrane constituents implicated in signaling and immune regulation. Synthesis of LPCs is challenging due to rapid acyl migration, e.g., induced by chromatography. We here report a highly regioselective synthesis of LPC and mixed PC via an intermediate allowing specific terminal acyl introduction, yielding the pure LPC without chromatography by an exceedingly mild TBS deprotection, using 1 equiv of TFA in aqueous solution. The method enabled the synthesis of glycerol-, acyl-, and choline-labeled LPC.
Topics: Lysophosphatidylcholines; Phosphatidylcholines; Water
PubMed: 35649118
DOI: 10.1021/acs.joc.2c00335 -
Dermatologic Surgery : Official... Jul 2023
Topics: Humans; Phosphatidylcholines; Blepharoplasty; Rhytidoplasty
PubMed: 37184452
DOI: 10.1097/DSS.0000000000003824 -
Contributions To Nephrology 1990
Review
Topics: Animals; Humans; Peritoneal Dialysis; Peritoneal Dialysis, Continuous Ambulatory; Phosphatidylcholines; Phospholipids; Ultrafiltration
PubMed: 2078933
DOI: 10.1159/000419074 -
Phosphatidylcholine biosynthesis and its significance in bacteria interacting with eukaryotic cells.European Journal of Cell Biology Dec 2010Phosphatidylcholine (PC), a typical eukaryotic membrane phospholipid, is present in only about 10% of all bacterial species, in particular in bacteria interacting with... (Review)
Review
Phosphatidylcholine (PC), a typical eukaryotic membrane phospholipid, is present in only about 10% of all bacterial species, in particular in bacteria interacting with eukaryotes. A number of studies revealed that PC plays a fundamental role in symbiotic and pathogenic microbe-host interactions. Agrobacterium tumefaciens mutants lacking PC are unable to elicit plant tumors. The human pathogens Brucella abortus and Legionella pneumophila require PC for full virulence. The plant symbionts Bradyrhizobium japonicum and Sinorhizobium meliloti depend on wild-type levels of PC to establish an efficient root nodule symbiosis. Two pathways for PC biosynthesis are known in bacteria, the methylation pathway and the phosphatidylcholine synthase (Pcs) pathway. The methylation pathway involves a three-step methylation of phosphatidylethanolamine by at least one phospholipid N-methyltransferase to yield phosphatidylcholine. In the Pcs pathway, choline is condensed directly with CDP-diacylglycerol to form PC. This review focuses on the biosynthetic pathways and the significance of PC in bacteria with an emphasis on plant-microbe interactions.
Topics: Animals; Bacteria; Eukaryotic Cells; Host-Pathogen Interactions; Humans; Phosphatidylcholines; Signal Transduction
PubMed: 20656373
DOI: 10.1016/j.ejcb.2010.06.013 -
Digestive Diseases (Basel, Switzerland) 2012The colonic mucus serves a first barrier towards invasion of commensal bacteria in stools to prevent inflammation. One essential component of intestinal mucus is... (Review)
Review
The colonic mucus serves a first barrier towards invasion of commensal bacteria in stools to prevent inflammation. One essential component of intestinal mucus is phosphatidylcholine (PC) which represents more than 90% of the phospholipids in mucus indicative for a selective transport of PC into this compartment. It is arranged in lamellar structures as surfactant-like particles which provide a hydrophobic surface on top of the hydrated mucus gel to prevent the invasion of bacteria from intestinal lumen. In ulcerative colitis (UC), the mucus PC content is reduced by 70%, irrespective of the state of inflammation. Thus, it could represent an intrinsic primary pathogenetic condition predisposing to bacterial invasion and the precipitation of inflammation. Since PC was shown to be mainly secreted by the ileal mucosa from where it is assumed to move distally to the colon, the PC content along the colonic wall towards the rectum gradually thins, with the least PC content in the rectum. This explains the start of the clinical manifestation of UC in the rectum and the expansion from there to the upper parts of the colon. In three clinical trials, when missing mucus PC in UC was supplemented by an oral, delayed release PC preparation, the inflammation improved and even resolved after a 3-month treatment course. The data indicate the essential role of the mucus PC content for protection against inflammation in colon.
Topics: Animals; Clinical Trials as Topic; Colitis, Ulcerative; Humans; Intestinal Mucosa; Mucus; Phosphatidylcholines; Protective Agents
PubMed: 23295697
DOI: 10.1159/000342729 -
Current Opinion in Lipidology Jun 2008This review summarizes the role of phosphatidylcholine metabolism in plasma lipoprotein homeostasis. (Review)
Review
PURPOSE OF REVIEW
This review summarizes the role of phosphatidylcholine metabolism in plasma lipoprotein homeostasis.
RECENT FINDINGS
While it was previously known that phosphatidylcholine biosynthesis was required for normal hepatic VLDL secretion, recent studies have shown that both phosphatidylcholine biosynthetic pathways (the cytidine 5'-diphosphocholine and the phosphatidylethanolamine methylation pathways) are required. In addition, a requirement of acyl-coenzyme A synthetase 3, but not acyl-coenzyme A synthetase 1 or 4, for phosphatidylcholine synthesis and VLDL secretion is now documented. ABCA1 has been implicated in the transfer of phosphatidylcholine to apolipoproteinA-1 both during and after secretion of apolipoproteinA-1. Other studies have introduced the concept of reverse phosphatidylcholine transport in which both HDL and LDL supply phosphatidylcholine to the liver. An unexpected finding is that half of the phosphatidylcholine delivered to liver from lipoproteins is converted into triacylglycerol.
SUMMARY
The liver is both a donor of phosphatidylcholine during the assembly and secretion of lipoproteins as well as a recipient of phosphatidylcholine from plasma lipoproteins.
Topics: Choline-Phosphate Cytidylyltransferase; Homeostasis; Lipoproteins, HDL; Lipoproteins, VLDL; Phosphatidylcholines; Phosphatidylethanolamine N-Methyltransferase; Phospholipid Transfer Proteins
PubMed: 18460912
DOI: 10.1097/MOL.0b013e3282fee935 -
Progress in Lipid Research Mar 2003Phosphatidylcholine (PC) is the major membrane-forming phospholipid in eukaryotes and can be synthesized by either of two pathways, the methylation pathway or the... (Review)
Review
Phosphatidylcholine (PC) is the major membrane-forming phospholipid in eukaryotes and can be synthesized by either of two pathways, the methylation pathway or the CDP-choline pathway. Many prokaryotes lack PC, but it can be found in significant amounts in membranes of rather diverse bacteria and based on genomic data, we estimate that more than 10% of all bacteria possess PC. Enzymatic methylation of phosphatidylethanolamine via the methylation pathway was thought to be the only biosynthetic pathway to yield PC in bacteria. However, a choline-dependent pathway for PC biosynthesis has been discovered in Sinorhizobium meliloti. In this pathway, PC synthase, condenses choline directly with CDP-diacylglyceride to form PC in one step. A number of symbiotic (Rhizobium leguminosarum, Mesorhizobium loti) and pathogenic (Agrobacterium tumefaciens, Brucella melitensis, Pseudomonas aeruginosa, Borrelia burgdorferi and Legionella pneumophila) bacteria seem to possess the PC synthase pathway and we suggest that the respective eukaryotic host functions as the provider of choline for this pathway. Pathogens entering their hosts through epithelia (Streptococcus pneumoniae, Haemophilus influenzae) require phosphocholine substitutions on their cell surface components that are biosynthetically also derived from choline supplied by the host. However, the incorporation of choline in these latter cases proceeds via choline phosphate and CDP-choline as intermediates. The occurrence of two intermediates in prokaryotes usually found as intermediates in the eukaryotic CDP-choline pathway for PC biosynthesis raises the question whether some bacteria might form PC via a CDP-choline pathway.
Topics: Bacteria; Diacylglycerol Cholinephosphotransferase; Genes, Bacterial; Methylation; Methyltransferases; Phosphatidylcholines
PubMed: 12547654
DOI: 10.1016/s0163-7827(02)00050-4