Sec14 is a cytosolic protein found in yeast ( Saccharomyces cerevisiae ) which plays a role in the regulation of several cellular functions, specifically those related to intracellular transport . Encoded by the Sec14 gene , Sec14p may transport phosphatidylinositol and phosphatidylcholine produced in the endoplasmic reticulum and the Golgi body to other cellular membranes. Additionally, Sec14p potentially plays a role in the localization of lipid raft proteins. Sec14p is an essential gene in yeast, and is homologous in function to phosphatidylinositol transfer protein in mammals. A conditional mutant with non-functional Sec14p presents with Berkeley bodies and deficiencies in protein secretion.
19-602: Sec14p exhibits two distinct domains, made up of twelve ⍺-helices, six 𝛽-strands, and eight 3 10 -helices. The phospholipid binding domain of Sec14p consists of a hydrophobic pocket within the carboxy-terminal domain. The function of Sec14p has largely been determined through the phenotype presented in conditional Sec14p mutants. As Sec14p is an essential gene, Sec14p knockouts must be performed in yeast strains with several other mutations conveying viability without functional Sec14p. In this knockout mutant, certain proteins destined for export accumulate in non-vesicular compartments of
38-417: A high proportion of dipalmitoylphosphatidylcholine . Phospholipase D catalyzes the hydrolysis of phosphatidylcholine to form phosphatidic acid (PA), releasing the soluble choline headgroup into the cytosol . A 2009 systematic review of clinical trials in humans found that there was not enough evidence to support supplementation of lecithin or phosphatidylcholine in dementia. The study found that
57-512: A lipid bilayer, discharges the bound phospholipid into the bilayer, and upon recognition of another membrane bound phospholipid, extracts the phospholipid and disassociates with the lipid bilayer. Additionally, the PtdIns and PtdCho affinity of Sec14p has been suggested to act as a localizing force, bringing Sec14p into proximity to the ER or Golgi body where it may aid in the formation of transport vesicles. In
76-437: A major component of lecithin that in some contexts the terms are sometimes used as synonyms. However, lecithin extracts consist of a mixture of phosphatidylcholine and other compounds. It is also used along with sodium taurocholate for simulating fed- and fasted-state biorelevant media in dissolution studies of highly lipophilic drugs. Phosphatidylcholine is a major constituent of cell membranes and pulmonary surfactant , and
95-509: A moderate benefit could not be ruled out until further large scale studies were performed. Though phosphatidylcholine has been studied as an alternative to liposuction , no peer-reviewed study has shown it to have comparable effects. Injection of phosphatidylcholine in lipomas has been studied, but the results have been mixed. Treatment of ulcerative colitis with oral intake of phosphatidylcholine has been shown to result in decreased disease activity. Although multiple pathways exist for
114-586: A variety of fatty acids. Usually, one is a saturated fatty acid (in the given figure, this is palmitic acid (hexadecanoic acid, H 3 C-(CH 2 ) 14 -COOH); margaric acid (heptadecanoic acid, H 3 C-(CH 2 ) 15 -COOH), identified by Gobley in egg yolk, also belong to that class); and the other is an unsaturated fatty acid (here oleic acid, or 9Z-octadecenoic acid, as in Gobley's original egg yolk lecithin). However, there are also examples of disaturated species. Animal lung phosphatidylcholine, for example, contains
133-542: A variety of readily available sources, such as egg yolk or soybeans , from which they are mechanically or chemically extracted using hexane . They are also a member of the lecithin group of yellow-brownish fatty substances occurring in animal and plant tissues. Dipalmitoylphosphatidylcholine (lecithin) is a major component of the pulmonary surfactant , and is often used in the lecithin–sphingomyelin ratio to calculate fetal lung maturity. While phosphatidylcholines are found in all plant and animal cells, they are absent in
152-416: Is considered generally recognized as safe (GRAS). Industrially, alpha-GPC is produced by the chemical or enzymatic deacylation of phosphatidylcholine enriched soya phospholipids followed by chromatographic purification . Alpha-GPC may also be derived in small amounts from highly purified soy lecithin as well as from purified sunflower lecithin. Alpha-GPC metabolizes to trimethylamine n-oxide in
171-535: Is essential in the budding of vesicles from the Golgi body, as it is thought to serve a function related to preserving diacylglycerol concentration in the Golgi body, a compound essential to secretory vesicle biosynthesis. The influence of Sec14p in the localization of lipid rafts is inferred due to abnormal localization and transport of lipid raft localized proteins in mutant yeast strains with non-functional Sec14p. Upon restoration of Sec14p function in these mutant strains,
190-403: Is more commonly found in the exoplasmic or outer leaflet of a cell membrane . It is thought to be transported between membranes within the cell by phosphatidylcholine transfer protein (PCTP). Phosphatidylcholine also plays a role in membrane-mediated cell signaling and PCTP activation of other enzymes. This phospholipid is composed of a choline head group and glycerophosphoric acid, with
209-437: The ability to bind PtdIns and PtdCho aids the intracellular transport function and regulation of Sec14p. This property may arise from potential transport of membrane lipids between the endoplasmic reticulum (ER) and the Golgi body by Sec14p to maintain an equilibrium in the membrane lipid concentration. Sec14p is thought to achieve phospholipid transport through phospholipid exchange. The protein-phospholipid complex associates with
SECTION 10
#1732858834354228-426: The biosynthesis of phosphatidylcholine, the predominant route in eukaryotes involves condensation between diacylglycerol (DAG) and cytidine 5'-diphosphocholine (CDP-choline or citicoline). The conversion is mediated by the enzyme diacylglycerol cholinephosphotransferase . Another pathway, mainly operative in the liver involves methylation of phosphatidylethanolamine with S -adenosyl methionine (SAM) being
247-447: The brain. It is also a parasympathomimetic acetylcholine precursor which has been investigated for its potential for the treatment of Alzheimer's disease and other dementias . Alpha-GPC rapidly delivers choline to the brain across the blood–brain barrier and is a biosynthetic precursor of acetylcholine . It is a non-prescription drug in most countries. The FDA determined that intake of no more than 196.2 mg/person/day
266-557: The cell, Sec14p plays an active and regulatory role in the intracellular transport of proteins. A good example of this function is the ability of Sec14p to both transport the phospholipids PtdIns and PtdCho between membranes as well as the inhibition of phospholipase D1 and phospholipase B1, which convert PtdCho to phosphatidic acid and choline or PtdCho to glycerophosphocholine , respectively. Sec14p and its homologs, some of which exhibit activation of phospholipase D1 and B1, aid in phospholipid metabolism regulation in vivo. Additionally, Sec14p
285-455: The cell. From this, functional Sec14p likely plays a role in some pathway responsible for cellular export of certain proteins. Protein accumulation in a Sec14p knockout is also accompanied by the formation of Berkeley bodies, an organelle unique to yeast consisting of cytoplasm enclosed by a double membrane. The presence of Berkeley bodies in Sec14p knockouts suggests Sec14p regulates or is involved in
304-402: The gastrointestinal tract, which has implications for cardiovascular health. In one study, risk of stroke over a ten-year period was increased by about 40% in users of alpha-GPC. Phosphatidylcholine Phosphatidylcholines ( PC ) are a class of phospholipids that incorporate choline as a headgroup . They are a major component of biological membranes and can be easily obtained from
323-496: The membranes of most bacteria, including Escherichia coli . Purified phosphatidylcholine is produced commercially. The name lecithin was derived from Greek λέκιθος, lekithos 'egg yolk' by Theodore Nicolas Gobley , a French chemist and pharmacist of the mid-19th century, who applied it to the egg yolk phosphatidylcholine that he identified in 1847. Gobley eventually completely described his lecithin from chemical structural point of view, in 1874. Phosphatidylcholines are such
342-493: The uptake and reabsorption of certain vesicles by other organelles, such as the Golgi body, or the plasma membrane of the cell. The accumulation of both Berkeley bodies and proteins in the cytosol indicate that Sec14p is involved in the formation and degradation of anterograde vesicles of certain proteins. In vitro, Sec14p has been demonstrated to catalyze the transport of phosphatidylinositol (PtdIns) and phosphatidylcholine (PtdCho) between lipid membranes. It has been suggested that
361-423: The wayward lipid raft proteins localized to their wild-type location. Experimental evidence suggests Sec14p may play a role in sorting proteins for incorporation into lipid rafts at the Golgi body prior to transport to the plasma membrane. Glycerophosphocholine L -α-Glycerophosphorylcholine ( alpha-GPC , choline alfoscerate , sn -glycero-3-phosphocholine ) is a natural choline compound found in
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