Metabolic and molecular aspects of ethanolamine phospholipid biosynthesis: the role of CTP:phosphoethanolamine cytidylyltransferase (Pcyt2)

2007 ◽  
Vol 85 (3) ◽  
pp. 283-300 ◽  
Author(s):  
Marica Bakovic ◽  
Morgan D. Fullerton ◽  
Vera Michel

The CDP-ethanolamine branch of the Kennedy pathway is the major route for the formation of ethanolamine-derived phospholipids, including diacyl phosphatidylethanolamine and alkenylacyl phosphatidylethanolamine derivatives, known as plasmalogens. Ethanolamine phospholipids are essential structural components of the cell membranes and play regulatory roles in cell division, cell signaling, activation, autophagy, and phagocytosis. The physiological importance of plasmalogens has not been not fully elucidated, although they are known for their antioxidant properties and deficiencies in a number of inherited peroxisomal disorders. This review highlights important aspects of ethanolamine phospholipid metabolism and reports current molecular information on 1 of the regulatory enzymes in their synthesis, CTP:phosphoethanolamine cytidylyltransferase (Pcyt2). Pcyt2 is encoded by a single, nonredundant gene in animal species that could be alternatively spliced into 2 potential protein products. We describe properties of the mouse and human Pcyt2 genes and their regulatory promoters and provide molecular evidence for the existence of 2 distinct Pcyt2 proteins. The goal is to obtain more insight into Pcyt2 catalytic function and regulation to facilitate a better understanding of the production of ethanolamine phospholipids via the CDP-ethanolamine branch of the Kennedy pathway.


2020 ◽  
Vol 133 (19) ◽  
pp. jcs249599 ◽  
Author(s):  
Destiny J. Davis ◽  
Minmin Wang ◽  
Iben Sørensen ◽  
Jocelyn K. C. Rose ◽  
David S. Domozych ◽  
...  

ABSTRACTCytokinesis in land plants involves the formation of a cell plate that develops into the new cell wall. Callose, a β-1,3 glucan, accumulates at later stages of cell plate development, presumably to stabilize this delicate membrane network during expansion. Cytokinetic callose is considered specific to multicellular plant species, because it has not been detected in unicellular algae. Here we present callose at the cytokinesis junction of the unicellular charophyte, Penium margaritaceum. Callose deposition at the division plane of P. margaritaceum showed distinct, spatiotemporal patterns likely representing distinct roles of this polymer in cytokinesis. Pharmacological inhibition of callose deposition by endosidin 7 resulted in cytokinesis defects, consistent with the essential role for this polymer in P. margaritaceum cell division. Cell wall deposition at the isthmus zone was also affected by the absence of callose, demonstrating the dynamic nature of new wall assembly in P. margaritaceum. The identification of candidate callose synthase genes provides molecular evidence for callose biosynthesis in P. margaritaceum. The evolutionary implications of cytokinetic callose in this unicellular zygnematopycean alga is discussed in the context of the conquest of land by plants.This article has an associated First Person interview with the first author of the paper.



1991 ◽  
Vol 69 (7) ◽  
pp. 463-474 ◽  
Author(s):  
Hugo W. Moser ◽  
Ann Bergin ◽  
David Cornblath

The concept that there are human disease states that are associated with abnormal peroxisomal function is of recent origin. This is due in part to the relatively recent discovery of the organelle itself by de Duve in 1983, and to the earlier belief that it was a vestigial structure in mammals. The recognition that the organelle is significant in mammals was ushered in by Paul Lazarow's observation that rat peroxisomes catalyze the β-oxidation of fatty acids. By 1981, more than 40 enzymes had been localized to the peroxisome, and the number continues to grow. Respect for the physiological role of the peroxisome in man has been heightened by our recent recognition that peroxisome malfunction causes profound disturbances. The Zellweger cerebro-hepato-renal syndrome represents the most serious peroxisomal disease. It is associated with malfunction of virtually every organ, and children with the disease usually do not survive beyond the 4th month. Application of newly developed diagnostic techniques has shown that the clinical spectrum and frequency of peroxisomal disorders are greater than had been realized. Eleven separate peroxisomal disorders have now been identified. Our laboratory alone has identified more than 2000 patients. Disturbances of very long chain fatty acid and ether phospholipid metabolism are present in 9 of the 11 peroxisomal disorders. In this presentation, we will provide an overview of the peroxisomal disorders, with emphasis on disturbances of fatty acid and ether lipid metabolism.Key words: peroxisomes, very long chain fatty acids, Zellweger syndrome, erucic acid, Refsum disease.



1972 ◽  
Vol 25 (1) ◽  
pp. 125 ◽  
Author(s):  
SJ Wysocki ◽  
W Segal

3H-1abelled ethanolamine phospholipids were isolated from the brains of 13-day-old rats after intracerebral injection of [9,1O-3H]palmitic acid. Groups of rats of the same age were injected intracerebrally with preparations derived from the whole labelled fraction, the ethanolamine plasmalogen-depleted fraction, or [14C]palmitic acid. A study of the distribution of radioactivity in phospholipids and sphingolipids, 2 hr after injection, indicates that the alkenyl chains of ethanolamine plasmalogen are effective precursors of the acyl groups of sphingomyelin and cere-broside. This role of plasmalogen is discussed in terms of the properties and distribu-tion of plasmalogenase, aldehyde dehydrogenase, and fatty acid chain-lengthening enzymes in brain.



Encyclopedia ◽  
2020 ◽  
Vol 1 (1) ◽  
pp. 65-75
Author(s):  
Daria A. Belinskaia ◽  
Polina A. Voronina ◽  
Anastasia A. Batalova ◽  
Nikolay V. Goncharov

Being one of the most abundant proteins in human and other mammals, albumin plays a crucial role in transporting various endogenous and exogenous molecules and maintaining of colloid osmotic pressure of the blood. It is not only the passive but also the active participant of the pharmacokinetic and toxicokinetic processes possessing a number of enzymatic activities. A free thiol group of the albumin molecule determines the participation of the protein in redox reactions. Its activity is not limited to interaction with other molecules entering the blood: of great physiological importance is its interaction with the cells of blood, blood vessels and also outside the vascular bed. This entry contains data on the enzymatic, inflammatory and antioxidant properties of serum albumin.



2020 ◽  
Author(s):  
Destiny J. Davis ◽  
Minmin Wang ◽  
Iben Sørensen ◽  
Jocelyn K.C. Rose ◽  
David S. Domozych ◽  
...  

AbstractCytokinesis in land plants involves the formation of a cell plate that develops into the new cell wall. Callose is a β-1,3 glucan that transiently accumulates at later stages of cell plate development and is thought to stabilize the delicate membrane network of the cell plate as it expands. Cytokinetic callose deposition is currently considered specific to multicellular plant species as it has not been detected in unicellular algae. Here we present callose at the cytokinesis junction of the unicellular charophyte, Penium margaritaceum. Notably, callose deposition at the division plane of P. margaritaceum showed distinct, spatiotemporal patterns that could represent distinct roles of this polymer in cytokinesis and cell wall assembly. Pharmacological inhibition of cytokinetic callose deposition by Endosidin 7 treatment resulted in cytokinesis defects, consistent with the essential role for this polymer in P. margaritaceum cell division. Cell wall deposition and assembly at the isthmus zone was also affected by the absence of callose, demonstrating the dynamic nature of new wall assembly in P. margaritaceum. The identification of candidate callose synthase genes provides molecular evidence for callose biosynthesis in P. margaritaceum. The evolutionary implications of cytokinetic callose in this unicellular Zygnematopycean alga is discussed in the context of the conquest of land by plants.Summary StatementEvolutionarily conserved callose in Penium margaritaceum is essential for the completion of cytokinesis.



Author(s):  
Chiara Vettraino ◽  
Alessio Peracchi ◽  
Stefano Donini ◽  
Emilio Parisini

Human O-phosphoethanolamine phospho-lyase (hEtnppl; EC 4.2.3.2) is a pyridoxal 5′-phosphate-dependent enzyme that catalyzes the degradation of O-phosphoethanolamine (PEA) into acetaldehyde, phosphate and ammonia. Physiologically, the enzyme is involved in phospholipid metabolism, as PEA is the precursor of phosphatidylethanolamine in the CDP-ethanolamine (Kennedy) pathway. Here, the crystal structure of hEtnppl in complex with pyridoxamine 5′-phosphate was determined at 2.05 Å resolution by molecular replacement using the structure of A1RDF1 from Arthrobacter aurescens TC1 (PDB entry 5g4i) as the search model. Structural analysis reveals that the two proteins share the same general fold and a similar arrangement of active-site residues. These results provide novel and useful information for the complete characterization of the human enzyme.



2017 ◽  
Vol 19 (suppl_6) ◽  
pp. vi130-vi130
Author(s):  
Pavithra Viswanath ◽  
Joanna J Phillips ◽  
Russell O Pieper ◽  
Sabrina Ronen


2021 ◽  
Author(s):  
Pradeep K Sheokand ◽  
Monika Narwal ◽  
Vandana Thakur ◽  
Asif Mohmmed

Phospholipid synthesis is crucial for membrane proliferation in malaria parasites during the entire cycle in the host cell. The major phospholipid of parasite membranes, phosphatidylcholine (PC), is mainly synthesized through the Kennedy pathway. The phosphocholine required for this synthetic pathway is generated by phosphorylation of choline derived from catabolism of the lyso-phosphatidylcholine (LPC) scavenged from the host milieu. Here we have characterized a Plasmodium falciparum lysophospholipase (PfLPL20) which showed enzymatic activity on LPC substrate to generate choline. Using GFP- targeting approach, PfLPL20 was localized in vesicular structures associated with the neutral lipid storage bodies present juxtaposed to the food-vacuole. The C-terminal tagged glmS mediated inducible knock-down of PfLPL20 caused transient hindrance in the parasite development, however, the parasites were able to multiply efficiently, suggesting that PfLPL20 is not essential for the parasite. However, in PfLPL20 depleted parasites, transcript levels of enzyme of SDPM pathway (Serine Decarboxylase-Phosphoethanolamine Methyltransferase) were altered along with upregulation of phosphocholine and SAM levels; these results show upregulation of alternate pathway to generate the phosphocholine required for PC synthesis through the Kennedy pathway. Our study highlights presence of alternate pathways for lipid homeostasis/membrane-biogenesis in the parasite; these data could be useful to design future therapeutic approaches targeting phospholipid metabolism in the parasite.



2019 ◽  
Vol 8 (6) ◽  
pp. 1035-1041
Author(s):  
Abhishek Raj ◽  
Vasanthi Nachiappan

Abstract Objective: To elucidate the impact of benzoquinone (BQ) on lipid homeostasis and cytotoxicity in Saccharomyces cerevisiae. Methods: The impact of BQ exposure on wild-type and knockouts of PC biosynthesizing genes revealed the alterations in the lipids that were analyzed by fluorescence microscopy, thin layer chromatography, and gene expression studies. Results: In yeast, BQ exposure reduced the growth pattern in wild-type cells. The gene knockout strains of the phospholipid metabolism altered the mRNA expression of the apoptosis genes – both caspase-dependent and independent. The BQ exposure revealed an increase in both the phospholipids and neutral lipids via the CDP:DAG and the Kennedy pathway genes. The accumulation of both neutral lipids and phospholipids during the BQ exposure was discrete and regulated by different pathways. Conclusions: BQ exposure inhibited cell growth, increased the reactive oxygen species (ROS), and altered membrane proliferation. The CDP:DAG and Kennedy pathway lipids also discretely altered by BQ, which is required for the membrane functions and energy purposes of life.



2020 ◽  
Vol 21 (22) ◽  
pp. 8833
Author(s):  
Pei-Jung Liu ◽  
Yu-Hsuan Chen ◽  
Kuo-Wang Tsai ◽  
Hui-Ying Yeah ◽  
Chung-Yu Yeh ◽  
...  

Lung cancer is the most prevalent types of cancer and the leading cause of cancer-related deaths worldwide. Among all cancers, lung cancer has the highest incidence, accompanied by a high mortality rate at the advanced stage. Favorable prognostic biomarkers can effectively increase the survival rate in lung cancer. Our results revealed FAM83A (Family with sequence similarity 83, member A) overexpression in lung cancer tissues compared with adjacent normal tissues. Furthermore, high FAM83A expression was closely associated with poor lung cancer survival. Here, through siRNA transfection, we effectively inhibited FAM83A expression in the lung cancer cell lines H1355 and A549. FAM83A knockdown significantly suppressed the proliferation, migration, and invasion ability of these cells. Furthermore, FAM83A knockdown could suppress Epidermal growth factor receptor (EGFR)/Mitogen-activated protein kinase (MAPK)/Choline kinase alpha (CHKA) signaling activation in A549 and H1355. By using a bioinformatics approach, we found that FAM83A overexpression in lung cancer may result from miR-1-3p downregulation. In summary, we identified a novel miR-1-FAM83A axis could partially modulate the EGFR/choline phospholipid metabolism signaling pathway, which suppressed lung cancer growth and motility. Our findings provide new insights for the development of lung cancer therapeutics.



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