While we were preparing our Sms1 KO mice, Yano et al16 reported that their Sms1 KO mice exhibited moderate neonatal lethality, reduced body weight, loss of fat tissue mass, β-cell mitochondrial dysfunction, and insulin secretion inhibition. We also found that the targeted allele was not segregated in a Mendelian fashion. Homozygous crosses did not yield viable progeny. We did not observe body weight reduction and the reason is unknown. In this study, we focused on plasma and tissue sphingolipid metabolism and examined atherosclerosis in Ldlr-/- mice that were transplanted with Sms1-deficient bone marrows. All these aspects were not investigated by the previous study.16. In this study, we have demonstrated for the first time that disruption of the Sms1 gene caused: (1) a significant reduction of SM levels in the plasma, macrophages, and liver, and marginal changes in ceramide levels; (2) a dramatic increase of glycosphingolipid levels in the plasma, macrophages, and liver; and (3) a significant ...
TY - JOUR. T1 - Long-chain bases of sphingolipids are transported into cells via the acyl-CoA synthetases. AU - Narita, Tomomi. AU - Naganuma, Tatsuro. AU - Sase, Yurie. AU - Kihara, Akio. PY - 2016/5/3. Y1 - 2016/5/3. N2 - Transport of dietary lipids into small-intestinal epithelial cells is pathologically and nutritionally important. However, lipid uptake remains an almost unexplored research area. Although we know that long-chain bases (LCBs), constituents of sphingolipids, can enter into cells efficiently, the molecular mechanism of LCB uptake is completely unclear. Here, we found that the yeast acyl-CoA synthetases (ACSs) Faa1 and Faa4 are redundantly involved in LCB uptake. In addition to fatty acid-activating activity, transporter activity toward long-chain fatty acids (LCFAs) has been suggested for ACSs. Both LCB and LCFA transports were largely impaired in faa1Δ faa4Δ cells. Furthermore, LCB and LCFA uptakes were mutually competitive. However, the energy dependency was different for ...
Sphingolipids such as ceramide and S1P have been recognized as bioactive lipids in cell death and proliferation/survival. In this review we overviewed role for sphingolipids in the induction of cell death in several types of hematological malignancies such as leukemia, malignant lymphoma and multiple myeloma. The main backbone molecule of sphingolipid network is ceramide. Ceramide is synthesized from serine and fatty acids with different kinds of carbon chains by de novo ceramide pathway in endoplasmic reticulum, and transferred to the Golgi apparatus by CERT for synthesis of SM by SMS while ceramide transfer protein for glucosylceramide to Golgi apparatus remains unknown. Sphingosine generated by CDase is phosphorylated and turns to S1P by SK1 or SK2. The complex sphingolipids such as glucosylceramide and GM3 are transferred to the micro-organelles to exert their functions and again returned to ceramide by salvage pathway. Likely, the catabolized sphingolipids such as sphingosine and ...
Mutations in Frataxin (FXN) cause Friedreichs ataxia (FRDA), a recessive neurodegenerative disorder. Previous studies have proposed that loss of FXN causes mitochondrial dysfunction, which triggers elevated reactive oxygen species (ROS) and leads to the demise of neurons. Here we describe a ROS independent mechanism that contributes to neurodegeneration in fly FXN mutants. We show that loss of frataxin homolog (fh) in Drosophila leads to iron toxicity, which in turn induces sphingolipid synthesis and ectopically activates 3-phosphoinositide dependent protein kinase-1 (Pdk1) and myocyte enhancer factor-2 (Mef2). Dampening iron toxicity, inhibiting sphingolipid synthesis by Myriocin, or reducing Pdk1 or Mef2 levels, all effectively suppress neurodegeneration in fh mutants. Moreover, increasing dihydrosphingosine activates Mef2 activity through PDK1 in mammalian neuronal cell line suggesting that the mechanisms are evolutionarily conserved. Our results indicate that an iron/sphingolipid/PDk1/Mef2 ...
The sphingolipid metabolites and genes (with the gene abbreviations shown in boxes, or enzyme names where gene names are ambiguous) are given for the condensation of serine and palmitoyl-CoA to form 3-ketosphinganine (3-ketoSa) by serine palmitoyltransferase, which is reduced to sphinganine (Sa), acylated to dihydroceramides, DHCer, by (DH)Cer synthases, and incorporated into more complex DH-sphingolipids (the 1-phosphate, DHCerP, sphingomyelins, DHSM, glucosylceramides, DHGlcCer, galactosylceramides, DHGalCer, lactosylceramides, DHLacCer, and sulfatides, or desaturated to Cer followed by headgroup addition. Also included are a number of the catabolic genes, e.g., sphingomyelinases, SMases, ceramidases, ASAH, sphingosine kinases, for the formation of sphinganine 1-phosphate (Sa1P) and sphingosine 1-phosphate (So1P), and phosphatases for the reverse reaction and the lyase that cleaves sphingoid base 1-phosphates to ethanolamine phosphate (EP), hexadecanal (C16:0al) and hexadecenal (C16:1al ...
Sphingolipids are fundamental to membrane trafficking, apoptosis and cell differentiation and proliferation. KDSR or 3-keto-dihydrosphingosine reductase is an essential enzyme for de novo sphingolipid synthesis, and pathogenic mutations in KDSR result in the severe skin disorder erythrokeratodermia variabilis et progressiva-4. Four of the eight reported cases also had thrombocytopenia but the underlying mechanism has remained unexplored. Here we expand upon the phenotypic spectrum of KDSR deficiency with studies in two siblings with novel compound heterozygous variants associated with thrombocytopenia, anemia and minimal skin involvement. We report a novel phenotype of progressive juvenile myelofibrosis in the propositus, with spontaneous recovery of anemia and thrombocytopenia in the first decade of life. Examination of bone marrow biopsies showed megakaryocyte hyperproliferation and dysplasia. Megakaryocytes obtained by culture of CD34+ stem cells confirmed hyperproliferation and showed ...
The objective of the present study was to evaluate sphingolipid levels (sphingosine-So and sphinganine-Sa) and to compare the Sa/So ratio in liver, serum and urine of Wistar rats after prolonged administration (21 days) of fumonisin B1 (FB1). In parallel, the kinetics of sphingolipid elimination in urine was studied in animals receiving a single dose of FB1. Prolonged exposure to FB1 caused an increase in Sa levels in urine, serum and liver. The most marked effect on sphingolipid biosynthesis was observed in animals treated with the highest dose of FB1. Animals receiving a single dose of FB1 presented variations in Sa and So levels and in the Sa/So ratio.
Author Summary One of the key components for hepatitis C virus (HCV) propagation is lipids, some of which comprise membranous replication complexes for HCV replication. Research on cofactors that are involved in the formation of the membranous replication complex has advanced steadily; on the other hand, the lipids constituting the membranous replication complex remain to be elucidated. Here, we report that HCV modulates sphingolipid metabolism by promoting sphingolipid biosynthesis, to enhance viral replication. Specifically a specific molecular species of sphingomyelin (SM), a type of sphingolipid interacts with HCV nonstructural 5B polymerase, enhancing HCV replication. This work highlights the relationship between specific molecular species of SMs and HCV replication, giving new insight into the formation of the HCV replication complex and the involvement of host lipids in the HCV life cycle.
Sphingolipids and PUFA are crucial bioactive molecules and involved in several fundamental and patho-physiological conditions like asthma, cystic fibrosis, respiratory tract infection and acute lung injuries. Among various intracellular kinases; Sphingosine kinase is crucial and central for Sphingolipids metabolism. SphK-1 is a well-known regulator of intracellular calcium homeostasis, cellular differentiation, innate immunity; apoptosis and cancer while the role of these lipids remains unclear. Sphingosine kinase-1 / has shown some therapeutic importance for controlling pulmonary infection with Mycobacteria. Therefore, the current topic is introduced to foster / welcome research activities across the globe targeting various sphingolipids and their derivatives for the effective management of pulmonary infection with pathogenic bacteria and discuss the therapeutic benefits of sphingolipid in controlling respiratory syndrome among various research groups/ labs for future collaboration.
As centenarians well represent the model of healthy aging, there are many important implications in revealing the underlying molecular mechanisms behind such successful aging. By combining NMR metabonomics and shot-gun lipidomics in serum we analyzed metabolome and lipidome composition of a group of centenarians with respect to elderly individuals. Specifically, NMR metabonomics profiling of serum revealed that centenarians are characterized by a metabolic phenotype distinct from that of elderly subjects, in particular regarding amino acids and lipid species. Shot-gun lipidomics approach displays unique changes in lipids biosynthesis in centenarians, with 41 differently abundant lipid species with respect to elderly subjects. These findings reveal phospho/sphingolipids as putative markers and biological modulators of healthy aging, in humans. Considering the particular actions of these metabolites, these data are suggestive of a better counteractive antioxidant capacity and a well-developed ...
Sphingolipids are a conserved family of lipids built upon a sphingoid base backbone. Sphingolipids serve structural membrane functions, whereas their metabolism...
Ceramide, a key intermediate in sphingolipid metabolism, is synthesized by acylation of sphinganine followed by dehydrogenation of dihydroceramide to ceramide. Using radioactive sphinganine, we have examined the site and topology of dihydroceramide synthesis in well-characterized subcellular fractions from rat liver. [4,5-3H]Sphinganine was introduced as a complex with BSA and was metabolized to [4,5-3H]dihydroceramide upon incubation of rat liver homogenates or microsomes with fatty acyl CoA. Conditions were established in a detergent-free system in which dihydroceramide synthesis was not limited by either substrate availability or by amounts of microsomal protein or reaction time. The distribution of dihydroceramide synthesis was found to exactly parallel that of an endoplasmic reticulum (ER) marker upon subfractionation of microsomes, and no endogenous activity was detected in either purified Golgi apparatus or plasma membrane fractions. Limited protease digestion demonstrated that ...
The human lipidome comprises over tens of thousands of distinct lipid species in addition to total cholesterol and the other conventional lipid traits that are routinely measurable in the peripheral circulation. Of the lipid species considered to exhibit bioactive functions, sphingolipids are a class of molecules that have shown relevance to human disease risk and cardiovascular outcomes in particular. In this issue of the JCI, Poss et al. conducted targeted lipidomics in a case-control study involving over 600 individuals and found a sphingolipid profile that predicted coronary artery disease status. In the context of emerging evidence linking sphingolipid biology with cardiovascular pathophysiology, these results suggest the potential utility of serum sphingolipids as cholesterol-independent markers of risk and even future targets for optimizing cardiovascular health.. ...
Research in recent years has shown that sphingolipids are essential signalling molecules for the proper biological and structural functioning of cells. Long-term studies on the metabolism of sphingolipids have provided evidence for their role in the pathogenesis of a number of diseases. As many inflammatory diseases, such as lysosomal storage disorders and some dermatologic diseases, including psoriasis, atopic dermatitis and ichthyoses, are associated with the altered composition and metabolism of sphingolipids, more studies precisely determining the responsibilities of these compounds for disease states are required to develop novel pharmacological treatment opportunities. It is worth emphasizing that knowledge from the study of inflammatory metabolic diseases and especially the possibility of their treatment may lead to insight into related metabolic pathways, including those involved in the formation of the epidermal barrier and providing new approaches towards workable therapies.
Sphingolipids are a family of membrane lipids with important structural roles in the regulation of the fluidity and subdomain structure of the lipid bilayer, es...
Plants exist in an environment of changing abiotic and biotic stresses. They have developed a complex set of strategies to respond to these stresses and over recent years it has become clear that sphingolipids are a key player in these responses. Sphingolipids are not universally present in all three domains of life. Many bacteria and archaea do not produce sphingolipids but they are ubiquitous in ...
Sphingolipids arent only important the different parts of membranes but possess features in proteins trafficking and intracellular signaling also. has been utilized to research the function of sphingolipid biosynthesis in heat surprise response (9-11) to differentiate between your contribution of de novo and degradative pathways in sphingolipid function (12) also to research trafficking and Isatoribine monohydrate function of solute transporters (13-15) the function of sphingolipids in membrane domains formation (16) as well as the intracellular transportation of glycosylphosphosphatidylinositol (GPI)-anchored protein (17 18 De novo synthesis of sphingolipids was initially been shown to be necessary for the transportation of GPI-anchored protein in the endoplasmic reticulum (ER) towards the Golgi area by breakthrough that myriocin (ISP-1) an inhibitor of SPT quickly inhibits this pathway (19). Eventually it was proven which the mutant is faulty in the same transportation stage (17). Another ...
Lipoproteins are major players in the development and progression of atherosclerotic plaques leading to coronary stenosis and myocardial infarction. Epidemiological, genetic and experimental observations have implicated the association of sphingolipids and intermediates of sphingolipid synthesis in atherosclerosis. We aimed to investigate relationships between quantitative changes in serum sphingolipids, the regulation of the metabolism of lipoproteins (LDL, HDL), and endophenotypes of coronary artery disease (CAD). We carried out untargeted liquid chromatography - mass spectrometry (UPLC-MS) lipidomics of serum samples of subjects belonging to a cross-sectional study and recruited on the basis of absence or presence of angiographically-defined CAD, and extensively characterized for clinical and biochemical phenotypes. Among the 2998 spectral features detected in the serum samples, 1328 metabolic features were significantly correlated with at least one of the clinical or biochemical phenotypes measured
... - reflects the multidimensional character of chemical biology, focusing in particular on the fundamental science of biological structures and systems, the use of chemical and biological techniques to elucidate
Sphingolipids are major constituents of membranes. A number of S. cerevisiae sphingolipid intermediates such as long chains sphingoid bases (LCBs) and ceramides act as signaling molecules regulating cell cycle progression, adaptability to heat stress, and survival in response to starvation. Here we …
FA2H Full-Length MS Protein Standard (NP_077282), Labeled with [U- 13C6, 15N4]-L-Arginine and [U- 13C6, 15N2]-L-Lysine, was produced in human 293 cells (HEK293) with fully chemically defined cell culture medium to obtain incorporation efficiency at Creative-Proteomics. This gene encodes a protein that catalyzes the synthesis of 2-hydroxysphingolipids, a subset of sphingolipids that contain 2-hydroxy fatty acids. Sphingolipids play roles in many cellular processes and their structural diversity arises from modification of the hydrophobic ceramide moiety, such as by 2-hydroxylation of the N-acyl chain, and the existence of many different head groups. Mutations in this gene have been associated with leukodystrophy dysmyelinating with spastic paraparesis with or without dystonia.
The lipids in the lipid bilayers of cell membranes are mainly phospholipids. When mixed with water, phospholipids and glycolipids form bilipid structures spontaneously. This is a result of the hydrophilic and strongly polar head of each lipid molecule, which contains sugar or phosphate, associating with water; and conversely, the non-polar alkyl tail of the fatty acyl groups aggregating by hydrophobic interactions.. Two types of phospholipids are glycerolphospholipids and sphingolipids.. Glycerophospholipids are composed fo a glycerol linked to two fatty acyl groups and one phosphate group, which could in turn be linked to other groups, including ethanolamine, choline, inositol, or serine, which are conventionally named, in these examples, as "phosphatidyl [other group name]," respectively.. Sphingolipids are composed of a sphingosine linked to one fatty acyl group. They are usually linked to a phosphate plus choline (sphingomyelin), sugar (ceramides), or complex oligosaccharide ...
TY - JOUR. T1 - The development and maintenance of paclitaxel-induced neuropathic pain require activation of the sphingosine 1-phosphate receptor subtype 1. AU - Janes, Kali. AU - Little, Joshua W.. AU - Li, Chao. AU - Bryant, Leesa. AU - Chen, Collin. AU - Chen, Zhoumou. AU - Kamocki, Krzysztof. AU - Doyle, Timothy. AU - Snider, Ashley. AU - Esposito, Emanuela. AU - Cuzzocrea, Salvatore. AU - Bieberich, Erhard. AU - Obeid, Lina. AU - Petrache, Irina. AU - Nicol, Grant. AU - Neumann, William L.. AU - Salvemini, Daniela. PY - 2014/7/25. Y1 - 2014/7/25. N2 - The ceramide-sphingosine 1-phosphate (S1P) rheostat is important in regulating cell fate. Several chemotherapeutic agents, including paclitaxel (Taxol), involve pro-apoptotic ceramide in their anticancer effects. The ceramide-to-S1P pathway is also implicated in the development of pain, raising the intriguing possibility that these sphingolipids may contribute to chemotherapyinduced painful peripheral neuropathy, which can be a critical ...
Eisosomes help sequester a subgroup of plasma membrane proteins into discrete membrane domains that colocalize with sites of endocytosis. Here we show that the major eisosome component Pil1 in vivo is a target of the long-chain base (LCB, the biosynthetic precursors to sphingolipids)-signaling pathway mediated by the Pkh-kinases. Eisosomes disassemble if Pil1 is hyperphosphorylated (i) upon overexpression of Pkh-kinases, (ii) upon reducing LCB concentrations by inhibiting serine-palmitoyl transferase in lcb1-mutant cells or by poisoning the enzyme with myriocin, and (iii) upon mimicking hyperphosphorylation in pil1-mutant cells. Conversely, more Pil1 assembles into eisosomes if Pil1 is hypophosphorylated (i) upon reducing Pkh-kinase activity in pkh1 pkh2-mutant cells, (ii) upon activating Pkh-kinases by addition of LCBs, and (iii) upon mimicking hypophosphorylation in pil1-mutant cells. The resulting enlarged eisosomes show altered organization. Other data suggest that Pkh signaling and ...
Vacuolar Membrane Protein; Transits Through The Biosynthetic Vacuolar Protein Sorting Pathway, Involved In Sphingolipid Metabolism; Cells Lacking Ncr1p Exhibit High Levels Of Long Chain Bases (LCB), Similar To The Accumulation Of High Amounts Of Lipids Observed In Patients With Neimann-Pick C, A Disease Caused By Loss-of-function Mutations In NPC1, The Functional Ortholog Of Ncr1p
A class of sphingolipids found largely in the brain and other nervous tissue. They contain phosphocholine or phosphoethanolamine as their polar head group so therefore are the only sphingolipids classified as PHOSPHOLIPIDS ...
With yeast this hypothesis can easily be tested, because a whole set of temperature-sensitive secretory mutants (Schekman, 1985) with defects at all stages along the secretory pathway of proteins is available. Secretory mutants selected for this study are listed in Table 1. If sphingolipids reach the plasma membrane by a process linked to protein secretion, temperature shift of secretory mutants from 24 to 37°C should not only inhibit protein secretion, but also affect the intracellular translocation of sphingolipids. Again, the kinetic and biochemical properties of cholesterol and marker protein transport to the PM are compared. The t1/2 of cholesterol transport to the PM was approximately 10 min (Kaplan and Simoni, 1985a), a value within the bounds of estimates of bulk membrane flow from the ER to the plasma membrane (Wieland et aL, 1987). This cholesterol transport required metabolic energy, exhibited a dramatic cold-sensitivity as transport ceased at 15°C, and labeled cholesterol ...
ARF6-GTP expression restores sphingolipid targeting to the Golgi.A, CtxB-AlexaFluor555 internalization in control (GM05659) and NPC mutant fibroblasts (GM03123,
GO:0030148. The chemical reactions and pathways resulting in the formation of sphingolipids, any of a class of lipids containing the long-chain amine diol sphingosine or a closely related base (a sphingoid). ...
A new paper is the first to report that specialized fat (lipid) molecules, called sphingolipids, play a key role in the survival of aggressive lymphomas
Sphingolipids play essential roles in various cellular events, including proliferation, differentiation, senescence, apoptosis, and inflammatory responses. Serine palmitoyltransferase (SPT) is the initial and rate-limiting enzyme in the de novo sphingolipid biosynthesis, and thus regulates the level of sphingolipids in cells. Immunohistochemical study revealed widespread distribution of the enzyme with most strong expression in brain and digestive tract. Two subunits, SPT1 and SPT2 at a stoichiometry of 1:1, are involved in the enzymatic activity of SPT. Synonyms: Long chain base biosynthesis protein 1; LCB-1; LCB1; Serine-palmitoyl-CoA transferase 1; SPT1; SPT 1; SPT-1 Product ...
Sphingolipids, or glycosylceramides, are a class of lipids containing a backbone of sphingoid bases, a set of aliphatic amino alcohols that includes sphingosine. They were discovered in brain extracts in the 1870s and were named after the mythological Sphinx because of their enigmatic nature. These compounds play important roles in signal transmission and cell recognition. Sphingolipidoses, or disorders of sphingolipid metabolism, have particular impact on neural tissue. A sphingolipid with an R group consisting of a hydrogen atom only is a ceramide. Other common R groups include phosphocholine, yielding a sphingomyelin, and various sugar monomers or dimers, yielding cerebrosides and globosides, respectively. Cerebrosides and globosides are collectively known as glycosphingolipids. The long-chain bases, sometimes simply known as sphingoid bases, are the first non-transient products of de novo sphingolipid synthesis in both yeast and mammals. These compounds, specifically known as ...
Sphingolipids are key components of eukaryotic membranes, particularly the plasma membrane. The biosynthetic pathway for the formation of these lipid species is largely conserved. However, in contrast to mammals, which produce sphingomyelin, organisms such as the pathogenic fungi and protozoa synthesize inositol phosphorylceramide (IPC) as the primary phosphosphingolipid. The key step involves the reaction of ceramide and phosphatidylinositol catalysed by IPC synthase, an essential enzyme with no mammalian equivalent encoded by the AUR1 gene in yeast and recently identified functional orthologues in the pathogenic kinetoplastid protozoa. As such this enzyme represents a promising target for novel anti-fungal and anti-protozoal drugs. Given the paucity of effective treatments for kinetoplastid diseases such as leishmaniasis, there is a need to characterize the protozoan enzyme. To this end a fluorescent-based cell-free assay protocol in a 96-well plate format has been established for the ...
Maintenance of sphingolipid homeostasis is critical for cell growth and programmed cell death (PCD). Serine palmitoyltransferase (SPT), composed of LCB1 and LCB2 subunits, catalyzes the primary regulatory point for sphingolipid synthesis. Small subunits of SPT (ssSPT) that strongly stimulate SPT activity have been identified in mammals, but the role of ssSPT in eukaryotic cells is unclear. Candidate Arabidopsis thaliana ssSPTs, ssSPTa and ssSPTb, were identified and characterized. Expression of these 56-amino acid polypeptides in a Saccharomyces cerevisiae SPT null mutant stimulated SPT activity from the Arabidopsis LCB1/LCB2 heterodimer by |100-fold through physical interaction with LCB1/LCB2. ssSPTa transcripts were more enriched in all organs and |400-fold more abundant in pollen than ssSPTb transcripts. Accordingly, homozygous ssSPTa T-DNA mutants were not recoverable, and 50% nonviable pollen was detected in heterozygous ssspta mutants. Pollen viability was recovered by expression of wild-type
BUFFALO, N.Y. - Youve probably never heard of "sphingolipids" before. But these curiously named organic compounds play a vital role in one of humanitys most well-known diseases: cancer.. Sphingolipids are a type of organic molecule found inside the body. Their odd appellation comes from the chemical "sphingosine," which forms one of the lipids building blocks and is said to have been named after the riddle-telling sphinx. (The famed scientist Johann Ludwig Wilhelm Thudichum wrote in 1884 that he chose to call the compound sphingosine "in commemoration of the many enigmas which it presented to the inquirer."). One mystery that remains today is the role that sphingolipids play in cancer - in particular, the way in which cancer cells die.. A new study by University at Buffalo scientists sheds light on this topic, tracing how levels of various sphingolipids spike inside cancer cells when the cells are undergoing a highly organized form of cellular death called apoptosis.. In normal cells, ...
Ceramide is a building block for complex sphingolipids in the plasma membrane, but it also plays a significant role in secondary signalling pathways regulating cell proliferation and apoptosis in response to stress. Ceramide activated protein phosphatase activity has been previously observed in association with the Sit4 protein phosphatase. Here we find that sit4Δ mutants have decreased ceramide levels and display resistance to exogenous ceramides and phytosphingosine. Mutants lacking SIT4 or KTI12 display a shift towards nonhydroxylated forms of long chain bases and sphingolipids, suggesting regulation of hydroxylase (SUR2) or ceramide synthase by Sit4p.We have identified novel subunits of the Sit4 complex and have also shown that known Sit4 regulatory subunits-SAP proteins-are not involved in the ceramide response. This is the first observation of separation of function between Sit4 and SAP proteins. We also find that the Sit4p target Elongator is not involved in the ceramide response but ...
EC 2.7.1.91. Accepted name: sphingosine kinase. Reaction: ATP + a sphingoid base = ADP + a sphingoid base 1-phosphate. Other name(s): SPHK1 (gene name); SPHK2 (gene name); dihydrosphingosine kinase; dihydrosphingosine kinase (phosphorylating); sphingosine kinase (phosphorylating); sphingoid base kinase; sphinganine kinase; ATP:sphinganine 1-phosphotransferase. Systematic name: ATP:sphingoid base 1-phosphotransferase. Comments: The enzyme is involved in the production of sphingolipid metabolites. It phosphorylates various sphingoid long-chain bases, such as sphingosine, D-erythro-dihydrosphingosine (sphinganine), phytosphingosine (4-hydroxysphinganine), 4-hydroxy-8-sphingenine, 4,8-sphingadienine and D-threo-dihydrosphingosine and L-threo-dihydrosphingosine. The exact substrate range depends on the species.. Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 50864-48-7. References:. 1. Stoffel, W., Heimann, G. and Hellenbroich, B. Sphingosine kinase in blood platelets. ...
Sphingoid bases (sphingosine, dihydrosphingosine and phytosphingosine) have been recently found in the oral cavity where they may serve to fortify innate immunity against commensals and periodontal pathogens. In fact, sphingoid bases have potent antimicrobial activity against Gram- positive and Gram- negative bacteria including oral pathogens like Porphyromonas gingivalis. It is not known whether these lipids are cytotoxic or alter the chemokine and cytokine responses of human dendritic cells, a finding important to their future potential as a therapeutic for treatment of periodontal disease. Objectives: The objective of this study was to determine the effects of sphingoid bases on the cytotoxicity and cytokine responses of human myeloid dendritic cells. Methods: Dendritic cells were treated with sphingoid bases (0.2-80.0 μM) for 16 hours in the presence or absence of 0.02 μM hemagglutinin B, a
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A modified RP-HPLC-MS approach has been proposed for a single run separation and identification of the molecular species of different phospholipid classes in a complex extract. This approach has been applied to the analysis of glycero- and sphingolipid composition of human erythrocytes and a number of ceramide fractions have been identified; these fractions was missed in previous studies employing similar methods. The fine experimental design leads to the decrease in the number of procedures needed for a complete phospholipid profiling of the sample ...
Fatty acid 2-hydroxylase is a protein that in humans is encoded by the FA2H gene. This gene encodes a protein that catalyzes the synthesis of 2-hydroxysphingolipids, a subset of sphingolipids that contain 2-hydroxy fatty acids. Sphingolipids play roles in many cellular processes and their structural diversity arises from modification of the hydrophobic ceramide moiety, such as by 2-hydroxylation of the N-acyl chain, and the existence of many different head groups. Mutations in this gene have been associated with leukodystrophy dysmyelinating with spastic paraparesis with or without dystonia as well as fatty acid hydroxylase-associated neurodegeneration. GRCh38: Ensembl release 89: ENSG00000103089 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000033579 - Ensembl, May 2017 "Human PubMed Reference:". "Mouse PubMed Reference:". "Entrez Gene: Fatty acid 2-hydroxylase". Retrieved 2011-12-30. Pierson TM, Simeonov DR, Sincan M, Adams DA, Markello T, Golas G, Fuentes-Fajardo K, Hansen NF, ...
Involved in the production of sphingolipid metabolites. Active on sphingosine, phytosphingosine (PHS, 4-hydroxysphinganine), D-erythro-dihydrosphingosine, D-erythro-sphingosine and trans-4, trans-8-sphingadienine, an LCB found exclusively in plants, but not on N-acetyl-dihydrosphingosine (C2-dihydroceramide) and D-threo-dihydrosphingosine.
Lipid rafts are thought to be highly dynamic, nanoscale (i.e., ,200 nm), cholesterol- and sphingolipid-enriched membrane microdomains, likely present in all eukaryotic cells, that compartmentalize select signaling and functional events. Although it is difficult to place a lower limit on their size in the resting state, and evidence indeed exists for "lipid shells" surrounding individual proteins in biological membranes (2), rafts can also be driven to coalesce into more stable, micrometer-range domains through lipid-lipid, protein-lipid, and protein-protein interactions. The mechanisms underlying raft "coalescence" or "clustering," however, in many cases remain elusive. It is generally thought that the saturated acyl chains of raft sphingolipids and phospholipids exhibit tight packing in a manner analogous to the liquid-ordered domains observed in model membranes, and that this may account for their resistance to solubilization by cold nonionic detergents (e.g., Triton X-100). However, as ...
Lipid rafts are thought to be highly dynamic, nanoscale (i.e., ,200 nm), cholesterol- and sphingolipid-enriched membrane microdomains, likely present in all eukaryotic cells, that compartmentalize select signaling and functional events. Although it is difficult to place a lower limit on their size in the resting state, and evidence indeed exists for "lipid shells" surrounding individual proteins in biological membranes (2), rafts can also be driven to coalesce into more stable, micrometer-range domains through lipid-lipid, protein-lipid, and protein-protein interactions. The mechanisms underlying raft "coalescence" or "clustering," however, in many cases remain elusive. It is generally thought that the saturated acyl chains of raft sphingolipids and phospholipids exhibit tight packing in a manner analogous to the liquid-ordered domains observed in model membranes, and that this may account for their resistance to solubilization by cold nonionic detergents (e.g., Triton X-100). However, as ...
Acer3 upregulation is important for the homeostasis of complex sphingolipid in aging brain.A and B. Levels of individual monohexosylceramide (HexCer) species an
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The SPTLC3 gene encodes an isoform of the third subunit of serine palmitoyltransferase (SPT; EC 2.3.1.50), which catalyzes the rate-limiting step of the de novo synthesis of sphingolipids (Hornemann et al., 2006 [PubMed 17023427]). SPT contains 2 main subunits: the common SPTLC1 subunit (MIM 605712) and either SPTLC2 (MIM 605713) or its isoform SPTLC2L (SPTLC3), depending on the tissue in which biosynthesis occurs (Hornemann et al., 2006 [PubMed 17023427]). There are also 2 highly related isoforms of a third subunit, SSSPTA (MIM 613540) and SSSPTB (MIM 610412), that confer acyl-CoA preference of the SPT enzyme and are essential for maximal enzyme activity (Han et al., 2009 [PubMed 19416851]).[supplied by OMIM, Nov 2010 ...
Lipids | sphingolipids | glycosphingolipids | gangliosides Definition: Gangliosides are glycosylated sphingolipids enriched in membranes of the (...)
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Study design. We evaluated the association of serum sphingolipids with CAD using existing samples and clinical and demographic information obtained from a case-control study conducted in Utah, USA (n = 462 patients; n = 212 controls) (57).. Study population. Patients were recruited between 1990 and 2000 from Intermountain Healthcare discharge records or the Family Health Tree Program in Utah (58). The patients were aged 30-75 years and had a diagnosis of CAD, defined by the original study recruitment criteria as MI, PTCA, or CABG. A large proportion of patients were male (77%), probably because premature CAD incidence rates are higher for men than women (59). The patients had an age of onset similar to that of at least 1 first-degree relative (parent, sibling, or child) (Table 1). To limit artifactual effects of the acute cardiac event on lipid levels, samples were collected at least 6 months following the event.. Control subjects representative of the Utah population (57, 60, 61) were randomly ...
Study design. We evaluated the association of serum sphingolipids with CAD using existing samples and clinical and demographic information obtained from a case-control study conducted in Utah, USA (n = 462 patients; n = 212 controls) (57).. Study population. Patients were recruited between 1990 and 2000 from Intermountain Healthcare discharge records or the Family Health Tree Program in Utah (58). The patients were aged 30-75 years and had a diagnosis of CAD, defined by the original study recruitment criteria as MI, PTCA, or CABG. A large proportion of patients were male (77%), probably because premature CAD incidence rates are higher for men than women (59). The patients had an age of onset similar to that of at least 1 first-degree relative (parent, sibling, or child) (Table 1). To limit artifactual effects of the acute cardiac event on lipid levels, samples were collected at least 6 months following the event.. Control subjects representative of the Utah population (57, 60, 61) were randomly ...