ASAH1CeramideDeficiencyLack of acid ceramidaseSphingolipidFatty acidsInhibitorAlkalineAmino acidGeneDegradationPfamIC50ActivityInhibitionNucleicMolecularSynthesisTargetingInhibitoryCellular250.100AccumulationGlutamicExpressionProteinResistanceHydroxylEssentialCellsHuman diseaseCancerCellBreaksEffect
ASAH16
- The ASAH1 gene codes for acid ceramidase, an enzyme found in lysosomes. (wikipedia.org)
- The ASAH1 gene provides instructions for making an enzyme called acid ceramidase. (medlineplus.gov)
- Variants in the ASAH1 gene lead to severe reduction in acid ceramidase, typically to below 10 percent of normal. (medlineplus.gov)
- Alves MQ, Le Trionnaire E, Ribeiro I, Carpentier S, Harzer K, Levade T, Ribeiro MG. Molecular basis of acid ceramidase deficiency in a neonatal form of Farber disease: identification of the first large deletion in ASAH1 gene. (medlineplus.gov)
- The maintenance of diminished acid ceramidase (ASAH1) gene expression leading to the accumulation of antiproliferative intracellular ceramides in oral squamous cell carcinoma (OSCC) has emerged as a prospective oral cancer therapeutic regimen. (bvsalud.org)
- Farber's disease and Spinal muscular atrophy-progressive myoclonic epilepsy are rare diseases that can be caused by variants in the ASAH1 gene that impair acid ceramidase enzyme activity. (nih.gov)
Ceramide14
- AC) is the lipid hydrolase responsible for the degradation of ceramide into sphingosine and free fatty acids within lysosomes. (nih.gov)
- Acid ceramidase (AC) is a lysosomal cysteine hydrolase that catalyzes the conversion of ceramide into fatty acid and sphingosine. (unipi.it)
- Adiponectin receptors (ADIPORs) are integral membrane proteins that control glucose and lipid metabolism by mediating, at least in part, a cellular ceramidase activity that catalyses the hydrolysis of ceramide to produce sphingosine and a free fatty acid (FFA). (nih.gov)
- Altogether, these data indicated that PEDHC produced by P. gingivalis inhibits acid ceramidase expression, promotes intracellular ceramide accumulation and suppresses the survival and migration of OSCC cells in vitro . (bvsalud.org)
- 7. Autophagy is increased in prostate cancer cells overexpressing acid ceramidase and enhances resistance to C6 ceramide. (nih.gov)
- It plays an important role in sphingolipid degradation by catalyzing the lysosomal hydrolysis of ceramide to sphingosine and free fatty acid. (nih.gov)
- Upon the stimulation of exogenous and endogenous factors, the sphingolipid (sphingomyelin) in endothelial cell membrane rafts undergoes hydrolysis by acid sphingomyelinase, releasing the hydrophilic phosphocholine group and generating hydrophobic item, ceramide [15]. (azd1152.com)
- Ypc1p can catalyze the reverse reaction, i.e. the condensation of free fatty acids with phytosphingosine or dihydrosphingosine and overexpression of YPC1 or YDC1 can provide enough ceramide synthesis as to rescue the viability of cells lacking the normal acyl-CoA-dependent ceramide synthases. (unifr.ch)
- To better understand the coexistence of acyl-CoA dependent ceramide synthases and ceramidases in the ER we investigated the membrane topology of Ypc1p by probing cysteine accessibility of natural and substituted cysteines with membrane non-permeating mass-tagged probes. (unifr.ch)
- 1, 2] Lipid substrates share a common structure, including a ceramide backbone (2-N-acyl-sphingosine), in which various sphingolipids are derived by substitution of hexoses, phosphorylcholine, or one or more sialic acid residues on terminal hydroxyl groups of the ceramide molecule. (medscape.com)
- Overexpression of sphingomyelin phosphodiesterase acid-like 3b (SMPDL3b) blocks ceramide kinase (CERK) activity and results in decreased ceramide to ceramide-1-phosphate (C1P) production. (scientificarchives.com)
- Increased production of ceramides is linked to elevated activity of serine palmitoyltransferase, the de novo ceramide synthesis pathway enzyme, in the presence of high glucose levels [6], while decreased activity of acid ceramidase, an enzyme responsible for degradation of ceramide, has been also reported in the hyperglycemia conditions in association with increased inflammatory response [7]. (scientificarchives.com)
- To elucidate the mechanisms that are involved in the decrease of ceramide levels in atopic dry skin and in aged skin, we examined both the activities of beta-glucocerebrosidase, which is a major enzyme in ceramide production, and of ceramidase, which is an essential enzyme in ceramide degradation, in the stratum corneum of atopic dry skin and aged skin. (medicaljournals.se)
- Ceramidases (EC 3.5.1.23), such as ASAH2, catalyze hydrolysis of the N-acyl linkage of ceramide, a second messenger in a variety of cellular events, to produce sphingosine. (utsouthwestern.edu)
Deficiency5
- Farber's disease is caused by the deficiency of the enzyme called ceramidase. (nih.gov)
- Inherited deficiency of acid ceramidase activity results in FARBER LIPOGRANULOMATOSIS . (nih.gov)
- In Gaucher disease (GD), the deficiency of glucocerebrosidase causes lysosomal accumulation of glucosylceramide (GlcCer), which is partly converted by acid ceramidase to glucosylsphingosine (GlcSph) in the lysosome. (amsterdamumc.org)
- To study the role of excessive GlcSph formation during glucocerebrosidase deficiency, we studied zebrafish that have two orthologs of acid ceramidase, Asah1a and Asah1b. (amsterdamumc.org)
- Dietary restriction has shown promise for disorders such as lysosomal acid lipase deficiency (Wolman disease), as has incorporation of lipid-lowering drugs in the regimen along with sebelipase alpha, a recombinant enzyme replacement therapy. (medscape.com)
Lack of acid ceramidase2
- The lack of myelin resulting from the lack of acid ceramidase breakdown leads to nerve cell dysfunction. (wikipedia.org)
- Farber's disease is characterized by a lack of acid ceramidase activity and N-oleoylethanolamine can be used to study aspects of this disease. (matreya.com)
Sphingolipid4
- 11. Ceramidases, roles in sphingolipid metabolism and in health and disease. (nih.gov)
- Dose dependent actions of LCL521 on acid ceramidase and key sphingolipid metabolites. (musc.edu)
- We found that OEA induced a significant reduction in hepatic triacylglycerol (TAG) content and significant changes in sphingolipid composition and ceramidase activity. (unich.it)
- Disturbance of sphingolipid composition at the plasma membrane due to increased activity of alkaline ceramidase 2 (ACER2) increases levels of sphingosine (Sph), which, together with increased activity of sphingosine kinases 1 and 2 (SPHK1/2), leads to increased production of S1P. (scientificarchives.com)
Fatty acids4
- Farber's disease (also known as Farber's lipogranulomatosis) is a one of a group of rare inherited metabolic disorders called lipid storage diseases, in which excess amounts of lipids (oils, fatty acids, and related compounds) build up to harmful levels in the central nervous system, joints, and tissues. (nih.gov)
- Unfortunately, traditional fatty acid oxidation does not work for branched-chain fatty acids, or fatty acids that do not have an even number of carbons, like the fatty acid phytanic acid, found in animal milk. (smpdb.ca)
- Notably, most of the synthesised RA accumulated as monoestolide triacylglycerols (ME TAGs), in which the RA hydroxyl group was masked by other fatty acids, which might explain its reduced cellular toxicity. (cell-metabolism.com)
- Two 12-desaturated fatty acids: 9,12-hexadecadienoic acid (16:29,12) and linoleic acid (LA, 18:29,12) were also detected in the ORF was cloned into an expression plasmid under the control of the promoter of the fucoxanthin chlorophyll a/c-binding protein 5 (with a clonNAT-resistant gene Astilbin IC50 expression cassette, which was used as a selection marker. (cell-metabolism.com)
Inhibitor4
- LCL521 known as an Stigmasterol (Stigmasterin) acid ceramidase inhibitor is worthy of detailed investigation. (immune-source.com)
- N-Oleoylethanolamine has been shown to be an efficacious inhibitor of acid ceramidase as well as an inhibitor of glucosylation of natural ceramides.1 It is specifically an inhibitor of the acid ceramidase found in human kidney and cerebellum with an IC50 of approximately 500μM. (matreya.com)
- Whereas the inhibitor D-MAPP potently inhibits alkaline ceramidase (IC50 approximately 5μM) N-oleoylethanolamine shows only slight inhibitory characteristics towards this ceramidase.2 N-Oleoylethanolamine is chemically related to the endocannabinoid anandamide, although it is not a cannabinoid itself. (matreya.com)
- Sarcosine (N-Methylglycine), an endogenous amino acid, is a competitive glycine transporter type I (GlyT1) inhibitor and N-methyl-D-aspartate (NMDA) receptor co-agonist. (medchemexpress.com)
Alkaline1
- HN - 2009 MH - Alkaline Ceramidase UI - D055574 MN - D8.811.277.87.250.300 MS - A ceramidase subtype that is active at alkaline pH. (nih.gov)
Amino acid2
- When this occurs, CRAF remains constitutively activated which leads to MEK/ERK activation.8C10 The most common mutation, accounting for 70C88% of all mutations, is a substitution of glutamic acid for valine at amino acid 600 (V600E).7,11 Other mutations in occur less frequently and include V600K, V600R, V600M, non-V600 alterations and fusions. (globaltechbiz.com)
- Supplementary Fig. S1), and one of these polymorphisms caused an amino acid substitution A327T (Supplementary Fig. S2). (cell-metabolism.com)
Gene1
- Ricinoleic acid (RA), a hydroxyl fatty acid, is suitable for medical and industrial uses and is produced in high-oil-accumulating organisms such as castor bean and the ergot fungus expressing the fatty acid hydroxylase gene (masks the hydroxyl group and accumulates RA as the less-toxic ME TAG. (cell-metabolism.com)
Degradation1
- In the majority of organisms, fatty acid degradation occurs mostly through the beta-oxidation cycle. (smpdb.ca)
Pfam1
- The data allow inferring that all amino acids of Ypc1p that are conserved in the pfam PF05875 ceramidase motif and the CREST superfamily are located in or near the ER lumen. (unifr.ch)
IC501
- 2004) suggested to use 3-(CR)-2-Carboxypiperazin-4-yl-propyl-1-phosphonic-acid (D-CPP), an MLN8054 IC50 NMDA channel blocker. (baxkyardgardener.com)
Activity5
- It is unclear whether the level of acid ceramidase activity is related to the severity of the disorder. (medlineplus.gov)
- 4. Novel off-target effect of tamoxifen--inhibition of acid ceramidase activity in cancer cells. (nih.gov)
- We associated the antiadipogenic effect of OEA to decreased activity and expression of key enzymes involved in fatty acid and TAG syntheses, such as acetyl-CoA carboxylase, fatty acid synthase, diacylglycerol acyltransferase, and stearoyl-CoA desaturase 1. (unich.it)
- Microsomal assays using a lysine-specific reagent show that the reverse ceramidase activity can only be blocked when the reagent has access to Ypc1p from the lumenal side. (unifr.ch)
- Azelaic acid is a dicarboxylic acid with known antimycotic activity. (medicaljournals.se)
Inhibition2
Nucleic2
- Red Nucleic Acid Gel Stain (10,000×) is a nucleic acid stain that can be used as a safer alternative to the traditional ethidium bromide (EB) stain for detecting nucleic acids in agarose gels or polyacrylamide gels. (medchemexpress.com)
- Compared to EB, Red Nucleic Acid Gel Stain (Red Stain) can't penetrate the cell membrane into cells above the working concentrations used in gel staining. (medchemexpress.com)
Molecular1
- Group 2 are penicillinases, cephalosporinases, or both inhibited by clavulanic acid, corresponding to the molecular classes A and D reflecting the original TEM and SHV genes. (wikidoc.org)
Synthesis1
- 2. Meister, A., Radhakrishnan, A.N. and Buckley, S.D. Enzymatic synthesis of L -pipecolic acid and L -proline. (qmul.ac.uk)
Targeting1
- 12. Targeting acid ceramidase sensitises head and neck cancer to cisplatin. (nih.gov)
Inhibitory1
- Inhibitory effect of Porphyromonas gingivalis-derived phosphoethanolamine dihydroceramide on acid ceramidase expression in oral squamous cells. (bvsalud.org)
Cellular1
- E2 binds to the protein acid ceramidase, which sets off a chain of cellular processes that suppress angiogenesis. (yonsei.ac.kr)
250.1001
- AN - coordinate with organ or disease /surg HN - 2009 MH - Acid Ceramidase UI - D055573 MN - D8.811.277.87.250.100 MS - A ceramidase subtype that is active at acid pH. (nih.gov)
Accumulation1
- Low-temperature-dependent ricinoleic acid production in Cp4 Optimal temperature conditions for RA accumulation were determined using Cp4 cells cultured at seven different temperatures: 10.0?C, 12.5?C, 15.0?C, 17.5?C, 20.0?C, 22.5?C, and 25?C. At 10.0?C and 12.5?C, the cells grew poorly, and the cell density (absorbance at 730?nm) failed to reach 1.0, even after 10 d (Supplementary Fig. S6). (cell-metabolism.com)
Glutamic1
- a) The promoter and coding regions of the glutamic acid decarboxylase (GAD) T\cell receptor (TCR) lentivector are depicted to scale. (neuroart2006.com)
Expression1
- 13. Increased acid ceramidase expression depends on upregulation of androgen-dependent deubiquitinases, USP2, in a human prostate cancer cell line, LNCaP. (nih.gov)
Protein1
- In order to determine how E2 works, the scientists then used a variety of advanced technologies to identify the protein that E2 binds to, which is known as acid ceramidase 1 (abbreviated as ASAHI). (yonsei.ac.kr)
Resistance2
- The overexpressed acid ceramidase was widely discovered on cancer cells, inducing apoptotic resistance on them.125 Therefore. (immune-source.com)
- 5. Radiation-induced acid ceramidase confers prostate cancer resistance and tumor relapse. (nih.gov)
Hydroxyl1
- In addition, the hydroxyl fatty acid (12OH-16:19), which was synthesised from 16:19 via CpFAH-catalysed hydroxylation, was also detected at 8.6?min (Supplementary Fig. S5), and the MS profiles of their trimethylsilyl derivatives including three diagnostic fragments at 159, 270, and 299 were identical to those reported previously2 (Supplementary Fig. S5). (cell-metabolism.com)
Essential1
- provided by C.G. Park) were cultured in Dulbecco's modified Eagle's medium (Invitrogen) containing 10% FBS and 1 non\essential amino acids. (neuroart2006.com)
Cells1
- 15. Potential role of acid ceramidase in conversion of cytostatic to cytotoxic end-point in pancreatic cancer cells. (nih.gov)
Human disease1
- Acid ceramidase and human disease. (nih.gov)
Cancer4
- 1. Acid ceramidase upregulation in prostate cancer: role in tumor development and implications for therapy. (nih.gov)
- 8. Acid ceramidase as a therapeutic target in metastatic prostate cancer. (nih.gov)
- 9. Acid ceramidase, an emerging target for anti-cancer and anti-angiogenesis. (nih.gov)
- 10. Acid Ceramidase: A Novel Therapeutic Target in Cancer. (nih.gov)
Cell2
- Somatostatin is stored in granules in the delta cell and is released in response to an increase in blood sugar, calcium, and blood amino acids during absorption of a meal. (smpdb.ca)
- Here, we report that a produced RA in photoautotrophic conditions, without any negative effects on cell growth, and that increased RA levels were achieved by co-expressing a palmitic acid (16:0)-specific fatty acid elongase, long chain fatty acid elongase1 (MALCE1). (cell-metabolism.com)
Breaks1
- Acid ceramidase breaks down fats called ceramides into a fat called sphingosine and a fatty acid. (medlineplus.gov)
Effect1
- In this study we have used an agar dilution technique to test the effect of six other dicarboxylic acids (sebacic, undecanedioic, dodecanedioic, tridecanedioic, tetradecanedioic and hexadecanedioic acid, 10(-4)-10(-2) mol/l, pH 5.5) on in vitro growth of Trichophyton (T.) rubrum, T. mentagrophytes and Microsporum (M.) canis. (medicaljournals.se)