A ceramidase subtype that is active at acid pH. It plays an important role in sphingolipid degradation by catalyzing the lysosomal hydrolysis of ceramide to sphingosine and free fatty acid. Inherited deficiency of acid ceramidase activity results in FARBER LIPOGRANULOMATOSIS.
An enzyme that catalyzes the hydrolysis of a ceramidetrihexoside to a ceramidedihexoside plus galactose.
A ceramidase subtype that is active at neutral pH. It is found at high levels within the SMALL INTESTINE and in the BRAIN.
Amidohydrolases that are specific for the cleavage of the N-acyl linkage of CERAMIDES. Ceramidases are classified as acidic, neutral or basic according to the optimal pH with which they function.
A ceramidase subtype that is active at alkaline pH. It is found at high levels within the SMALL INTESTINE.
A sphingolipidosis subtype that is characterized by the histological appearance of granulomatous deposits in tissues. It results from the accumulation of CERAMIDES in various tissues due to an inherited deficiency of ACID CERAMIDASE.
Members of the class of neutral glycosphingolipids. They are the basic units of SPHINGOLIPIDS. They are sphingoids attached via their amino groups to a long chain fatty acyl group. They abnormally accumulate in FABRY DISEASE.
Amidohydrolases are enzymes that catalyze the hydrolysis of amides and related compounds, playing a crucial role in various biological processes including the breakdown and synthesis of bioactive molecules.
An amino alcohol with a long unsaturated hydrocarbon chain. Sphingosine and its derivative sphinganine are the major bases of the sphingolipids in mammals. (Dorland, 28th ed)
A class of membrane lipids that have a polar head and two nonpolar tails. They are composed of one molecule of the long-chain amino alcohol sphingosine (4-sphingenine) or one of its derivatives, one molecule of a long-chain acid, a polar head alcohol and sometimes phosphoric acid in diester linkage at the polar head group. (Lehninger et al, Principles of Biochemistry, 2nd ed)
Salts and esters of the 14-carbon saturated monocarboxylic acid--myristic acid.
An enzyme that catalyzes the hydrolysis of sphingomyelin to ceramide (N-acylsphingosine) plus choline phosphate. A defect in this enzyme leads to NIEMANN-PICK DISEASE. EC 3.1.4.12.
A family of glycoprotein cofactors that are required for the efficient catabolization of SPHINGOLIPIDS by specific acid hydrolases such as GLUCOSYLCERAMIDASE; GALACTOCEREBROSIDASE; BETA-N-ACETYLHEXOSAMINIDASE; and CEREBROSIDE-SULFATASE.
GLYCEROL esterified with a single acyl (FATTY ACIDS) chain.
Inborn errors of metabolism characterized by defects in specific lysosomal hydrolases and resulting in intracellular accumulation of unmetabolized substrates.
Derivatives of PHOSPHATIDIC ACIDS that lack one of its fatty acyl chains due to its hydrolytic removal.
Phosphoric acid esters of dolichol.
A group of four homologous sphingolipid activator proteins that are formed from proteolytic cleavage of a common protein precursor molecule referred to as prosaposin.

Specific and sensitive assay for alkaline and neutral ceramidases involving C12-NBD-ceramide. (1/51)

A fluorescent analogue of ceramide, C12-NBD-ceramide, was found to be hydrolyzed much faster than 14C-labeled ceramide by alkaline ceramidase from Pseudomonas aeruginosa and neutral ceramidase from mouse liver, while this substrate was relatively resistant to acid ceramidase from plasma of the horseshoe crab. The radioactive substrate was used more preferentially by the acid ceramidase. It should be noted that C6-NBD-ceramide, which is usually used for ceramidase assays, was hardly hydrolyzed by any of the enzymes examined, compared to C12-NBD-ceramide. For the alkaline and neutral enzymes, the Vmax and k (Vmax/Km) with C12-NBD-ceramide were much higher than those with 14C-ceramide. In contrast, for the acid enzyme these parameters with C12-NBD-ceramide were less than half those with the radioisotope-labeled substrate. It is noteworthy that the labeling of ceramide with NBD did not itself reduce the Km of the alkaline enzyme, but did that of the neutral enzyme. It was also found that C12-NBD-ceramide was preferentially hydrolyzed by the alkaline and neutral enzymes, but not the acid one, in several mammalian cell lines. This study clearly shows that the attachment of NBD, but not dansyl, increases the susceptibility of ceramide to alkaline and neutral enzyme, and decreases that to acid enzymes. Thus the use of this substrate provides a specific and sensitive assay for alkaline and neutral ceramidases.  (+info)

Molecular cloning, sequencing, and expression of the gene encoding alkaline ceramidase from Pseudomonas aeruginosa. Cloning of a ceramidase homologue from Mycobacterium tuberculosis. (2/51)

We previously reported the purification and characterization of a novel type of alkaline ceramidase from Pseudomonas aeruginosa strain AN17 (Okino, N., Tani, M., Imayama, S., and Ito, M. (1998) J. Biol. Chem. 273, 14368-14373). Here, we report the molecular cloning, sequencing, and expression of the gene encoding the ceramidase of this strain. Specific oligonucleotide primers were synthesized using the peptide sequences of the purified ceramidase obtained by digestion with lysylendopeptidase and used for polymerase chain reaction. DNA fragments thus amplified were used as probes to clone the gene encoding the ceramidase from a genomic library of strain AN17. The open reading frame of 2,010 nucleotides encoded a polypeptide of 670 amino acids including a signal sequence of 24 residues, 64 residues of which matched the amino acid sequence determined for the purified enzyme. The molecular weight of the mature enzyme was estimated to be 70,767 from the deduced amino acid sequence. Expression of the ceramidase gene in Escherichia coli, resulted in production of a soluble enzyme with the identical N-terminal amino acid sequence. Recombinant ceramidase was purified to homogeneity from the lysate of E. coli cells and confirmed to be identical to the Pseudomonas enzyme in its specificity and other enzymatic properties. No significant sequence similarities were found in other known functional proteins including human acid ceramidase. However, we found a sequence homologous to the ceramidase in hypothetical proteins encoded in Mycobacterium tuberculosis, Dictyostelium discoideum, and Arabidopsis thaliana. The homologue of the ceramidase gene was thus cloned from an M. tuberculosis cosmid and expressed in E. coli, and the gene was demonstrated to encode an alkaline ceramidase. This is the first report for the cloning of an alkaline ceramidase.  (+info)

Overexpression of acid ceramidase protects from tumor necrosis factor-induced cell death. (3/51)

Tumor necrosis factor (TNF) signals cell death and simultaneously induces generation of ceramide. To evaluate the contribution of ceramide to TNF-dependent cell death, we generated clones of the TNF-sensitive cell line L929 that constitutively overexpress human acid ceramidase (AC). Ceramidase, in concert with sphingosine kinase, metabolizes ceramide to sphingosine-1-phosphate (SPP), an inducer of proliferation. In response to TNF, parental L929 cells display a significant increase in intracellular ceramide correlated with an "atypical apoptosis" characterized by membrane blebbing, DNA fragmentation and degradation of poly(ADP-ribose) polymerase despite a lack of caspase activity. These features are strongly reduced or absent in AC-overexpressing cells. Pharmacological suppression of AC with N-oleoylethanolamine restored the accumulation of intracellular ceramide as well as the sensitivity of the transfectants to TNF, implying that an enhanced metabolization of intracellular ceramide by AC shifts the balance between intracellular ceramide and SPP levels towards cell survival. Correspondingly, inhibition of ceramide production by acid sphingomyelinase also increased survival of TNF-treated L929 cells.  (+info)

Bcl-2 overexpression prevents apoptosis induced by ceramidase inhibitors in malignant melanoma and HaCaT keratinocytes. (4/51)

We examined the biological effects of the ceramide analogues (1S,2R)-2-N-myristoylamino-1-phenyl-1-propanol (D-e-MAPP) and (1R,2R)-2-N-myristoylamino-1-(4-nitrophenyl)-1,3-propandiol (D-NMAPPD) on human HaCaT keratinocytes and human melanoma cells. We could demonstrate that D-e-MAPP and D-NMAPPD are able to suppress acid ceramidase activity. The elevation of the endogenous level of ceramide is followed by induction of apoptosis and suppression of proliferation in HaCaT keratinocytes. Moreover, we recently identified a group of human melanoma cell populations which are heterogeneously susceptible to C2-ceramide-mediated apoptosis. Studies with these melanoma cells revealed correlation between ceramide-mediated apoptosis and D-NMAPPD-induced apoptosis, confirming the effect of this inhibitor on ceramide signaling in human melanoma cells. These findings suggest ceramidase inhibitors as a potential new therapeutical class of antiproliferative and cytostatic drugs.  (+info)

The reverse activity of human acid ceramidase. (5/51)

An overexpression system was recently developed to produce and purify recombinant, human acid ceramidase. In addition to ceramide hydrolysis, the purified enzyme was able to catalyze ceramide synthesis using [14C]lauric acid and sphingosine as substrates. Herein we report detailed characterization of this acid ceramidase-associated "reverse activity" and provide evidence that this reaction occurs in situ as well as in vitro. The pH optimum of the reverse reaction was approximately 5.5, as compared with approximately 4.5 for the hydrolysis reaction. Non-ionic detergents and zinc cations inhibited the activity, whereas most other cations were stimulatory. Of note, sphingomyelin also was very inhibitory toward this reaction, whereas the anionic lipids, phosphatidic acid and phosphatidylserine, were stimulatory. Of various sphingosine stereoisomers tested in the reverse reaction, only the natural, D-erythro form could efficiently serve as a substrate. Using D-erythro-sphingosine and lauric acid as substrates, the reaction followed normal Michaelis-Menten kinetics. The Km and Vmax values toward sphingosine were 23.75 microM and 208.3 pmol/microg/h, respectively, whereas for lauric acid they were 73.76 microM and 232.5 pmol/microg/h, respectively. Importantly, the reverse activity was reduced in cell lysates from a Farber disease patient to the same extent as the acid ceramidase activity. Furthermore, when 12-(N-methyl-N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)) (NBD)-conjugated lauric acid and sphingosine were added to cultured lymphoblasts from a Farber disease patient in the presence of fumonisin B (1), the conversion to NBD-ceramide was reduced approximately 30% when compared with normal cells. These data provide important new information on human acid ceramidase and further document its central role in sphingolipid metabolism.  (+info)

Stress-induced apoptosis is impaired in cells with a lysosomal targeting defect but is not affected in cells synthesizing a catalytically inactive cathepsin D. (6/51)

The role of cathepsin D in stress-induced cell death has been investigated by using ovine fibroblasts exhibiting a missense mutation in the active site of cathepsin D. The cathepsin D (lysosomal aspartic protease) deficiency did not protect cells against toxicity induced by doxorubicin and other cytotoxic agents, neither did it protect cells from caspase activation. Moreover, the cathepsin D inhibitor, pepstatin A, did not prevent stress-induced cell death in human fibroblasts or lymphoblasts. The possible role of lysosomal ceramide or sphingosine-mediated activation of cathepsin D in apoptosis was also excluded by using human cells either overexpressing or deficient in acid ceramidase. However, a normal lysosomal function seems to be required for efficient cell death, as indicated by the finding that fibroblasts from patients with mucolipidosis II were partially resistant to staurosporine, sphingosine and TNF-induced apoptosis, suggesting a key role of lysosomes in cell death.  (+info)

Upregulation of the human alkaline ceramidase 1 and acid ceramidase mediates calcium-induced differentiation of epidermal keratinocytes. (7/51)

Extracellular calcium (Ca2+(o)) potently induces the growth arrest and differentiation of human epidermal keratinocytes (HEKs). We report that Ca2+(o) markedly upregulates the human alkaline ceramidase 1 (haCER1) in HEKs; and its upregulation mediates the Ca2+(o)-induced growth arrest and differentiation of HEKs. haCER1 is the human ortholog of mouse alkaline ceramidase 1 that we previously identified. haCER1 catalyzed the hydrolysis of very long-chain ceramides to generate sphingosine (SPH). This in vitro activity required Ca2+. Ectopic expression of haCER1 in HEKs decreased the levels of D-e-C(24:1)-ceramide and D-e-C(24:0)-ceramide but elevated the levels of both SPH and its phosphate (S1P), whereas RNA interference-mediated knockdown of haCER1 caused the opposite effects on the levels of these sphingolipids in HEKs. Similar to haCER1 overexpression, Ca2+(o) increased the levels of SPH and S1P, and this was attenuated by haCER1 knockdown. haCER1 knockdown also inhibited the Ca2+(o)-induced growth arrest of HEKs and the Ca2+(o)-induced expression of keratin 1 and involucrin in HEKs. In addition, the acid ceramidase (AC) was also upregulated by Ca2+(o); and its knockdown attenuated the Ca2+(o)-induced expression of keratin 1 and involucrin in HEKs. These results strongly suggest that upregulation of haCER1 and AC mediates the Ca2+(o)-induced growth arrest and differentiation of HEKs by generating SPH and S1P.  (+info)

Population genetic analysis of the N-acylsphingosine amidohydrolase gene associated with mental activity in humans. (8/51)

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Acid ceramidase is an enzyme that plays a role in the metabolism of ceramides, which are lipid molecules found in cell membranes. Specifically, acid ceramidase helps to break down ceramides into sphingosine and free fatty acids. This enzyme is active at an acidic pH and is located in the lysosomes, which are organelles within cells that help to break down and recycle various materials.

Defects in the gene that provides instructions for making acid ceramidase can lead to a condition called Farber disease, which is characterized by the accumulation of ceramides in various tissues and organs. This can cause a range of symptoms, including joint pain, muscle weakness, and developmental delays.

Galactosylgalactosylglucosylceramidase is a type of enzyme that is involved in the breakdown and recycling of complex lipids called glycosphingolipids in the body. More specifically, it helps to break down a particular type of glycosphingolipid known as globotriaosylceramide (Gb3 or CD77) into simpler components.

This enzyme is critical for maintaining the health and function of various tissues in the body, including the nervous system. Deficiencies in galactosylgalactosylglucosylceramidase have been linked to a number of serious genetic disorders, such as Tay-Sachs disease and Sandhoff disease, which are characterized by the accumulation of Gb3 and other glycosphingolipids in various tissues, leading to progressive neurological deterioration and other symptoms.

Neutral ceramidase is an enzyme that plays a role in the metabolism of sphingolipids, which are a type of lipid found in cell membranes. Specifically, neutral ceramidase catalyzes the conversion of ceramide to sphingosine and free fatty acid. This reaction takes place at a neutral pH, hence the name "neutral" ceramidase.

Ceramide is a key component of the lipid bilayer in cell membranes and is also involved in various signaling pathways related to cell growth, differentiation, and apoptosis (programmed cell death). The conversion of ceramide to sphingosine by neutral ceramidase helps to regulate these processes.

Abnormal levels or activity of neutral ceramidase have been implicated in various diseases, including cancer, inflammation, and neurodegenerative disorders. For example, increased activity of this enzyme has been observed in some types of cancer, which may contribute to tumor growth and progression. On the other hand, decreased activity of neutral ceramidase has been linked to inflammatory conditions and neurodegenerative diseases such as Alzheimer's disease.

Ceramidases are a group of enzymes that catalyze the hydrolysis of ceramide into sphingosine and free fatty acids. Ceramides are important components of cell membranes, and their metabolism is tightly regulated in cells. The hydrolysis of ceramide by ceramidases produces sphingosine, which can be further phosphorylated to form sphingosine-1-phosphate (S1P), a signaling molecule involved in various cellular processes such as proliferation, differentiation, and survival.

There are several types of ceramidases that have been identified, including acid ceramidase, neutral ceramidase, and alkaline ceramidase. These enzymes differ in their subcellular localization, substrate specificity, and physiological functions. Dysregulation of ceramidase activity has been implicated in various diseases, including cancer, neurodegenerative disorders, and inflammatory conditions. Therefore, ceramidases are considered as potential therapeutic targets for the treatment of these diseases.

Alkaline ceramidase is a type of enzyme that belongs to the family of hydrolases, specifically those acting on ester bonds. This enzyme's function is to catalyze the hydrolysis of ceramides into sphingosine and free fatty acids. Ceramides are important lipid molecules found in cell membranes, and their metabolism plays a crucial role in various biological processes such as cell differentiation, proliferation, and apoptosis.

Alkaline ceramidase is localized in the endoplasmic reticulum and Golgi apparatus of cells and has an optimum pH range between 8.5 to 9.5. It is involved in several physiological processes, including skin barrier formation, inflammation, and cancer development. Mutations in the gene that encodes for alkaline ceramidase have been associated with various diseases such as Farber's lipogranulomatosis, a rare genetic disorder characterized by accumulation of ceramides in tissues leading to joint pain, hoarseness, and progressive intellectual disability.

Farber Lipogranulomatosis is a rare genetic disorder characterized by the accumulation of fatty substances (lipids) in various tissues and organs of the body. This condition is also known as Farber's disease or Infantile Ceramidase Deficiency. It is caused by mutations in the ASAH1 gene, which leads to a deficiency in the enzyme acid ceramidase. As a result, lipids accumulate in cells, causing inflammation and the formation of granulomas.

The symptoms of Farber Lipogranulomatosis typically appear within the first few months of life and can include:

* Subcutaneous nodules (small lumps under the skin) that are painful and tender to the touch
* Hoarseness or weakened cry due to inflammation in the voice box (larynx)
* Joint stiffness and pain due to lipid accumulation in the synovial fluid of joints
* Difficulty swallowing and feeding due to lipid accumulation in the muscles used for swallowing
* Slow growth and development
* Respiratory problems, including recurrent pneumonia and bronchitis

There is no cure for Farber Lipogranulomatosis, but treatment can help manage the symptoms. This may include physical therapy to improve joint mobility, medications to reduce inflammation and pain, and feeding tubes to ensure adequate nutrition. In some cases, bone marrow transplantation may be considered as a potential treatment option.

Ceramides are a type of lipid molecule that are found naturally in the outer layer of the skin (the stratum corneum). They play a crucial role in maintaining the barrier function and hydration of the skin. Ceramides help to seal in moisture, support the structure of the skin, and protect against environmental stressors such as pollution and bacteria.

In addition to their role in the skin, ceramides have also been studied for their potential therapeutic benefits in various medical conditions. For example, abnormal levels of ceramides have been implicated in several diseases, including diabetes, cardiovascular disease, and cancer. As a result, ceramide-based therapies are being investigated as potential treatments for these conditions.

Medically, ceramides may be mentioned in the context of skin disorders or diseases where there is a disruption in the skin's barrier function, such as eczema, psoriasis, and ichthyosis. In these cases, ceramide-based therapies may be used to help restore the skin's natural barrier and improve its overall health and appearance.

Amidohydrolases are a class of enzymes that catalyze the hydrolysis of amides and related compounds, resulting in the formation of an acid and an alcohol. This reaction is also known as amide hydrolysis or amide bond cleavage. Amidohydrolases play important roles in various biological processes, including the metabolism of xenobiotics (foreign substances) and endogenous compounds (those naturally produced within an organism).

The term "amidohydrolase" is a broad one that encompasses several specific types of enzymes, such as proteases, esterases, lipases, and nitrilases. These enzymes have different substrate specificities and catalytic mechanisms but share the common ability to hydrolyze amide bonds.

Proteases, for example, are a major group of amidohydrolases that specifically cleave peptide bonds in proteins. They are involved in various physiological processes, such as protein degradation, digestion, and regulation of biological pathways. Esterases and lipases hydrolyze ester bonds in various substrates, including lipids and other organic compounds. Nitrilases convert nitriles into carboxylic acids and ammonia by cleaving the nitrile bond (C≡N) through hydrolysis.

Amidohydrolases are found in various organisms, from bacteria to humans, and have diverse applications in industry, agriculture, and medicine. For instance, they can be used for the production of pharmaceuticals, biofuels, detergents, and other chemicals. Additionally, inhibitors of amidohydrolases can serve as therapeutic agents for treating various diseases, such as cancer, viral infections, and neurodegenerative disorders.

Sphingosine is not a medical term per se, but rather a biological compound with importance in the field of medicine. It is a type of sphingolipid, a class of lipids that are crucial components of cell membranes. Sphingosine itself is a secondary alcohol with an amino group and two long-chain hydrocarbons.

Medically, sphingosine is significant due to its role as a precursor in the synthesis of other sphingolipids, such as ceramides, sphingomyelins, and gangliosides, which are involved in various cellular processes like signal transduction, cell growth, differentiation, and apoptosis (programmed cell death).

Moreover, sphingosine-1-phosphate (S1P), a derivative of sphingosine, is an important bioactive lipid mediator that regulates various physiological functions, including immune response, vascular maturation, and neuronal development. Dysregulation of S1P signaling has been implicated in several diseases, such as cancer, inflammation, and cardiovascular disorders.

In summary, sphingosine is a crucial biological compound with medical relevance due to its role as a precursor for various sphingolipids involved in cellular processes and as a precursor for the bioactive lipid mediator S1P.

Sphingolipids are a class of lipids that contain a sphingosine base, which is a long-chain amino alcohol with an unsaturated bond and an amino group. They are important components of animal cell membranes, particularly in the nervous system. Sphingolipids include ceramides, sphingomyelins, and glycosphingolipids.

Ceramides consist of a sphingosine base linked to a fatty acid through an amide bond. They play important roles in cell signaling, membrane structure, and apoptosis (programmed cell death).

Sphingomyelins are formed when ceramides combine with phosphorylcholine, resulting in the formation of a polar head group. Sphingomyelins are major components of the myelin sheath that surrounds nerve cells and are involved in signal transduction and membrane structure.

Glycosphingolipids contain one or more sugar residues attached to the ceramide backbone, forming complex structures that play important roles in cell recognition, adhesion, and signaling. Abnormalities in sphingolipid metabolism have been linked to various diseases, including neurological disorders, cancer, and cardiovascular disease.

Myristates are fatty acid molecules that contain fourteen carbon atoms and are therefore referred to as myristic acid in its pure form. They are commonly found in various natural sources, including coconut oil, palm kernel oil, and butterfat. Myristates can be esterified with glycerol to form triglycerides, which are the main constituents of fat in animals and plants.

In a medical context, myristates may be relevant in the study of lipid metabolism, membrane biology, and drug delivery systems. For instance, myristoylation is a post-translational modification where myristic acid is covalently attached to proteins, which can affect their function, localization, and stability. However, it's important to note that direct medical applications or implications of myristates may require further research and context.

Sphingomyelin phosphodiesterase is an enzyme that catalyzes the hydrolysis of sphingomyelin, a sphingolipid found in animal tissues, into ceramide and phosphorylcholine. This enzyme plays a crucial role in the metabolism of sphingomyelin and the regulation of cellular processes such as apoptosis, differentiation, and inflammation.

There are several isoforms of this enzyme, including acid sphingomyelinase (ASM) and neutral sphingomyelinase (NSM), which differ in their subcellular localization, regulation, and physiological functions. Deficiencies or dysfunctions in sphingomyelin phosphodiesterase activity have been implicated in various diseases, such as Niemann-Pick disease, atherosclerosis, and cancer.

Sphingolipid activator proteins (SAPs), also known as saposins, are a group of small proteins that play a crucial role in the metabolism of sphingolipids, a class of lipids found in cell membranes. These proteins are produced by the cleavage of a precursor protein called prosaposin.

SAPs facilitate the hydrolysis of sphingolipids by activating specific lysosomal hydrolases, enzymes that break down these lipids into simpler molecules. Each SAP has a unique structure and function, and they are named SapA, SapB, SapC, and SapD.

SapA and SapB activate the enzyme glucocerebrosidase, which breaks down glucosylceramide into glucose and ceramide. SapC activates the enzyme galactocerebrosidase, which breaks down galactosylceramide into galactose and ceramide. SapD has multiple functions, including activating the enzyme acid sphingomyelinase, which breaks down sphingomyelin into ceramide and phosphorylcholine.

Deficiencies in SAPs can lead to lysosomal storage disorders, such as Gaucher disease (caused by a deficiency in glucocerebrosidase) and Krabbe disease (caused by a deficiency in galactocerebrosidase). These disorders are characterized by the accumulation of undigested sphingolipids in various tissues, leading to cell dysfunction and tissue damage.

Medical Definition of Monoglycerides:

Monoglycerides are types of glycerides that contain one molecule of fatty acid combined with a glycerol molecule through an ester linkage. They are often used as food additives, serving as emulsifiers to help blend together water and oil-based ingredients in foods such as baked goods, ice cream, and chocolate. Monoglycerides can also be found naturally in some foods, including certain vegetable oils.

In the context of human physiology, monoglycerides can serve as a source of energy and can also play a role in the absorption and transport of fatty acids in the body. However, they are not typically considered to be a major nutrient or component of the human diet.

Lysosomal storage diseases (LSDs) are a group of rare inherited metabolic disorders caused by defects in lysosomal function. Lysosomes are membrane-bound organelles within cells that contain enzymes responsible for breaking down and recycling various biomolecules, such as proteins, lipids, and carbohydrates. In LSDs, the absence or deficiency of specific lysosomal enzymes leads to the accumulation of undigested substrates within the lysosomes, resulting in cellular dysfunction and organ damage.

These disorders can affect various organs and systems in the body, including the brain, nervous system, bones, skin, and visceral organs. Symptoms may include developmental delays, neurological impairment, motor dysfunction, bone abnormalities, coarse facial features, hepatosplenomegaly (enlarged liver and spleen), and recurrent infections.

Examples of LSDs include Gaucher disease, Tay-Sachs disease, Niemann-Pick disease, Fabry disease, Pompe disease, and mucopolysaccharidoses (MPS). Treatment options for LSDs may include enzyme replacement therapy, substrate reduction therapy, or bone marrow transplantation. Early diagnosis and intervention can help improve the prognosis and quality of life for affected individuals.

Lysophospholipids are a type of glycerophospholipid, which is a major component of cell membranes. They are characterized by having only one fatty acid chain attached to the glycerol backbone, as opposed to two in regular phospholipids. This results in a more polar and charged molecule, which can play important roles in cell signaling and regulation.

Lysophospholipids can be derived from the breakdown of regular phospholipids through the action of enzymes such as phospholipase A1 or A2. They can also be synthesized de novo in the cell. Some lysophospholipids, such as lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P), have been found to act as signaling molecules that bind to specific G protein-coupled receptors and regulate various cellular processes, including proliferation, survival, and migration.

Abnormal levels of lysophospholipids have been implicated in several diseases, such as cancer, inflammation, and neurological disorders. Therefore, understanding the biology of lysophospholipids has important implications for developing new therapeutic strategies.

Dolichol phosphates are a type of lipid molecule that play a crucial role in the process of protein glycosylation within the endoplasmic reticulum of eukaryotic cells. Glycosylation is the attachment of carbohydrate groups, or oligosaccharides, to proteins and lipids.

Dolichol phosphates consist of a long, isoprenoid hydrocarbon chain that is attached to two phosphate groups. The hydrocarbon chain can vary in length but typically contains between 10 and 20 isoprene units. These molecules serve as the anchor for the oligosaccharides during the glycosylation process.

In the first step of protein glycosylation, an oligosaccharide is synthesized on a dolichol phosphate molecule through the sequential addition of sugar residues by a series of enzymes. Once the oligosaccharide is complete, it is transferred to the target protein in a process called "oligosaccharyltransferase" (OST)-mediated transfer. This transfer results in the formation of a glycoprotein, which can then undergo further modifications as it moves through the secretory pathway.

Defects in dolichol phosphate metabolism have been linked to various genetic disorders, such as congenital disorder of glycosylation (CDG) types Ib and Id, which are characterized by abnormal protein glycosylation and a wide range of clinical manifestations, including developmental delay, neurological impairment, and multi-systemic involvement.

Saposins are a group of naturally occurring lipid-binding proteins that play an essential role in the metabolism of lipids within cells. They are named after a skin disease called "Niemann-Pick disease," where defects in saposin function lead to an accumulation of lipids in various tissues, including the brain.

There are four types of saposins (SapA, SapB, SapC, and SapD) that are produced by the cleavage of a larger precursor protein called prosaposin. These proteins help to facilitate the breakdown of lipids in lysosomes, which are specialized organelles within cells that break down and recycle various materials.

Saposins play an important role in activating certain enzymes that are involved in breaking down lipids, such as sphingolipids and gangliosides. They do this by binding to these enzymes and presenting them with their lipid substrates in a way that allows the enzymes to efficiently break them down.

Defects in saposin function can lead to a variety of diseases, including Niemann-Pick disease, Gaucher disease, and Krabbe disease, which are characterized by an accumulation of lipids in various tissues and neurological symptoms.

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In chronic myelogenous leukemia (CML), IRF8 regulates acid ceramidase to mediate CML apoptosis. IRF8 is highly expressed in ... "IRF8 regulates acid ceramidase expression to mediate apoptosis and suppresses myelogeneous leukemia". Cancer Res. 71 (8): 2882- ...
S1P is formed from ceramide, which is composed of a sphingosine and a fatty acid. Ceramidase, an enzyme primarily present in ... Lipid signaling Lysophosphatidic acid Mendelson, Karen; Evans, Todd; Hla, Timothy (1 January 2014). "Sphingosine 1-phosphate ... October 2000). "Oocyte apoptosis is suppressed by disruption of the acid sphingomyelinase gene or by sphingosine-1-phosphate ... Progress in Nucleic Acid Research and Molecular Biology. 71: 493-511. doi:10.1016/s0079-6603(02)71049-0. ISBN 9780125400718. ...
2005). "Elevation of the level and activity of acid ceramidase in Alzheimer's disease brain". Eur. J. Neurosci. 20 (12): 3489- ... This gene encodes an N-acylethanolamine-hydrolyzing enzyme which is highly similar to acid ceramidase. Multiple transcript ... "Entrez Gene: ASAHL N-acylsphingosine amidohydrolase (acid ceramidase)-like". Human NAAA genome location and NAAA gene details ... Schulze H, Schepers U, Sandhoff K (2008). "Overexpression and mass spectrometry analysis of mature human acid ceramidase". Biol ...
Presently, 7 human ceramidases encoded by 7 distinct genes have been cloned: acid ceramidase (ASAH1) - cell survival neutral ... Ceramidase at the U.S. National Library of Medicine Medical Subject Headings (MeSH) EC 3.5.1.23 Portal: Biology v t e (EC 3.5.1 ... Human neutral ceramidase (nCDase) is an enzyme that plays a critical role in colon cancer and there are currently no potent or ... Ceramidase (EC 3.5.1.23, acylsphingosine deacylase, glycosphingolipid ceramide deacylase) is an enzyme which cleaves fatty ...
NAAA is homologous to acid ceramidase (HUGO gene symbol: ASAH1), sharing 30% sequence identity at the amino acid level in ... its structural similarity to the more familiar acid ceramidase (AC) and functional similarity to fatty acid amide hydrolase ( ... NAAA's primary structure is nearly identical to that of acid ceramidase (AC), whose only difference is the substitution of Leu ... a novel member of the choloylglycine hydrolase family with structural and functional similarity to acid ceramidase". The ...
... can be further hydrolyzed by acid ceramidase to form sphingosine and a free fatty acid, both of which are able to ... A ceramide is composed of sphingosine and a fatty acid joined by an amide bond. Ceramides are found in high concentrations ... Rotolo JA, Zhang J, Donepudi M, Lee H, Fuks Z, Kolesnick R (2005). "Caspase-dependent and -independent activation of acid ... Anandamide Ceramidase inhibitors Chemotherapeutic agents Fas ligand Endotoxin Homocysteine Heat Hydroxypalmitoyl Sphinganine ...
... and they identified acid ceramidase as the enzyme deficient in Farber's disease. In 1964, Moser returned to the Joseph P. ... Together, they organized a symposium at Kennedy Krieger where Bill Rizzo presented data that showed that adding oleic acid (C- ... Yasuo Kishimoto, who had helped Kuni Suzuki make the discovery of elevated very long chain fatty acids in Adrenoleukodystrophy ... Odone made an independent intellectual computation - namely that the use of erucic acid, which is C-22:1 (C-22 monounsaturated ...
Fatty Acid Amide Hydrolase inhibitors), PEA (N-Acylethanolamide Acid Amidase inhibitors), and ceramide (Acid Ceramidase ... "Discovery of highly potent acid ceramidase inhibitors with in vitro tumor chemosensitizing activity". Science Reports 3:1035. ... "Selective N-acylethanolamine-hydrolyzing acid amidase inhibition reveals a key role for endogenous palmitoylethanolamide in ...
... acid ceramidase), an enzymatic product of ASAH1, gene mutated in Farber disease Australian Society for Asian Humanities This ...
... acid ceramidase) 1 ASPH: encoding enzyme Aspartyl/asparaginyl beta-hydroxylase AZIN1: encoding protein Antizyme inhibitor 1 ... fatty acid binding protein 9, testis FAM167A: family with sequence similarity 167, member A FAM203B: family with sequence ...
... sialic acid storage disease Infantile free sialic acid storage disease Glycogen storage diseases Type II Pompe disease Type IIb ... Lysosomal storage diseases include: Sphingolipidoses Ceramidase Farber disease Krabbe disease Infantile onset Late onset ... Cystinosis is an lysosomal storage disease characterized by the abnormal accumulation of the amino acid cystine. Alternatively ... Chronic hexosaminidase A deficiency Glucocerebroside Gaucher disease Type I Type II Type III Sphingomyelinase Lysosomal acid ...
... ceramidase converts ceramide to sphingosine) and blocks the effects of TNF- and arachidonic acid on intracellular Ca2+ ... to eicosatetraenoic acid (ETA: C20H32O2; 20:4-n3; omega-3 Arachidonic acid) and arachidonic acid (AA: C20H32O2; 20:4-n6) to ... and heptadecanoic acid (C17H34O2; 17:0), elevated palmitoleic acid (POA; C16H30O2; 16:1, n-7), a conjugate acid of a ... where n-7 fatty acids are precursors for the production of omega-4 fatty acids like palmitolinoleic acid (16:2), and a ...
The activity may be that of an acid phosphatase EC 3.1.3.31: The activity may be that of an acid phosphatase EC 3.1.3.32: ... ceramidase EC 3.5.1.24: choloylglycine hydrolase EC 3.5.1.25: N-acetylglucosamine-6-phosphate deacetylase EC 3.5.1.26: N4-(β-N- ... ABC-type polar-amino-acid transporter EC 3.6.3.22: Now EC 7.4.2.2, ABC-type nonpolar-amino-acid transporter EC 3.6.3.23: Now EC ... EC 3.1.2.25: phenylacetyl-CoA hydrolase EC 3.1.2.26: Now EC 2.8.3.25, bile acid CoA transferase EC 3.1.2.27: choloyl-CoA ...
"Cooperative prosurvival activity by ERK and Akt in human alveolar macrophages is dependent on high levels of acid ceramidase ... Neutral ceramidase is an enzyme that in humans is encoded by the ASAH2 gene. GRCh38: Ensembl release 89: ENSG00000188611 - ... 2004). "Neutral ceramidase gene: role in regulating ceramide-induced apoptosis". Gene. 315: 113-22. doi:10.1016/S0378-1119(03) ... 2006). "Golgi alkaline ceramidase regulates cell proliferation and survival by controlling levels of sphingosine and S1P". ...
A brief, very comprehensible review is given in Gunstone, F. (1996) Fatty Acid and Lipid Chemistry, pp 43-44. Blackie Academic ... Finally, ceramide may be broken down by a ceramidase to form sphingosine. Sphingosine may be phosphorylated to form sphingosine ... Gangliosides have at least three sugars, one of which must be sialic acid. Inositol-containing ceramides, which are derived ... such as a fatty acid.[citation needed] Simple sphingolipids, which include the sphingoid bases and ceramides, make up the early ...
"Docosahexaenoic acid-derived fatty acid esters of hydroxy fatty acids (FAHFAs) with anti-inflammatory properties". Diabetes. 65 ... Sphingosine (Sph) is formed by the action of ceramidase (CDase) enzymes on ceramide in the lysosome. Sph can also be formed in ... Palmitic acid esters of hydroxy-stearic acids (PAHSAs) are among the most bioactive members able to activate G-protein coupled ... Docosahexaenoic acid ester of hydroxy-linoleic acid (DHAHLA) exert anti-inflammatory and pro-resolving properties. ...
Folic acid uptake was dramatically inhibited. Treatment after exposure with folic acid reduced neural tube defects by 50-65%. ... de formation via de novo sphinganine and fatty acyl-CoA and via sphingosine produced by the breakdown of ceramide by ceramidase ... However, when the tricarbillic acid groups are removed from FB1 by hydrolysis, the resulting product (aminopentol, AP1) doesn't ... whereas the negatively charged tricarbyllic acid groups may interact with the fatty acyl-CoA binding site. Because FB1 also ...
Roca, X. (2003-11-01). "Intrinsic differences between authentic and cryptic 5' splice sites". Nucleic Acids Research. 31 (21): ... "A neutral ceramidase, NlnCDase, is involved in the stress responses of brown planthopper, Nilaparvata lugens (Stål)". ... Nucleic Acids Research. 37 (9): e67. doi:10.1093/nar/gkp215. ISSN 1362-4962. PMC 2685110. PMID 19339519. "Splice-Site Analyzer ... Nucleic Acids Research. 37 (Web Server): W189-W192. doi:10.1093/nar/gkp320. ISSN 0305-1048. PMC 2703896. PMID 19429896. Damiola ...
Unlike acid and neutral SMases in the intestinal tract that are rapidly inactivated by pancreatic trypsin, alk-SMase is ... neutral ceramidase, and sphingolipid metabolites". Pediatr. Res. 61 (1): 61-6. doi:10.1203/01.pdr.0000250534.92934.c2. PMID ... Besides, ursodeoxycholic acid and probiotic VSL#3 may stimulate the expression of ENPP7 in the intestine. GRCh38: Ensembl ... Liu F, Cheng Y, Wu J, Tauschel HD, Duan RD (April 2006). "Ursodeoxycholic acid differentially affects three types of ...
The ASAH1 gene codes for acid ceramidase, an enzyme found in lysosomes. The lysosome breaks down acid ceramidase; the fatty ... The lack of myelin resulting from the lack of acid ceramidase breakdown leads to nerve cell dysfunction.[citation needed] ... Park, Jae-Ho; Schuchman, Edward H. (December 2006). "Acid ceramidase and human disease". Biochimica et Biophysica Acta (BBA) - ... "Acid ceramidase deficiency associated with spinal muscular atrophy with progressive myoclonic epilepsy". Neuromuscular ...
Acid ceramidase breaks down fats called ceramides into a fat called sphingosine and a fatty acid. These two breakdown products ... Molecular basis of acid ceramidase deficiency in a neonatal form of Farber disease: identification of the first large deletion ... Acid ceramidase deficiency: Farber disease and SMA-PME. Orphanet J Rare Dis. 2018 Jul 20;13(1):121. doi: 10.1186/s13023-018- ... Variants in the ASAH1 gene lead to severe reduction in acid ceramidase, typically to below 10 percent of normal. As a result, ...
The maintenance of diminished acid ceramidase (ASAH1) gene expression leading to the accumulation of antiproliferative ... Altogether, these data indicated that PEDHC produced by P. gingivalis inhibits acid ceramidase expression, promotes ... Inhibitory effect of Porphyromonas gingivalis-derived phosphoethanolamine dihydroceramide on acid ceramidase expression in oral ... Ceramidase Ácida/genética Estudos Prospectivos Células Epiteliais/metabolismo Ceramidas Carcinoma de Células Escamosas de ...
AdipoR, Adiponectin receptor; ASAH1, Acid ceramidase 1; β-AR, β-adrenergic receptor; CERS1-6, Ceramide synthase 1-6; DES1-2, ... with ceramidases, and ability of human AdipoRs to promote ceramidase activity in ceramidase deficient yeast, the Scherer group ... A role for ceramide, but not diacylglycerol, in the antagonism of insulin signal transduction by saturated fatty acids. J Biol ... TLR4 links innate immunity and fatty acid-induced insulin resistance. J Clin Invest. (2006) 116:3015-25. doi: 10.1172/JCI28898 ...
Farbers disease (lysosomal acid ceramidase deficiency). (1 July, 1987) Free R A Jameson, P J Holt, J H Keen ...
Lead Optimization of Benzoxazolone Carboxamides as Orally Bioavailable and CNS Penetrant Acid Ceramidase Inhibitors. Di Martino ... Benzoxazolone Carboxamides as Potent Acid Ceramidase Inhibitors: Synthesis and Structure-Activity Relationship (SAR) Studies. ... octane Sulfonamides as a Novel Class of Non-Covalent N-Acylethanolamine-Hydrolyzing Acid Amidase (NAAA) Inhibitors for Oral ...
ASAH1, also named as AC, ACDase, Acid CDase, PHP32 and ASAH, belongs to the acid ceramidase family. ASAH1 is a lipid hydrolase ... Acid ceramidase inhibition ameliorates α-synuclein accumulation upon loss of GBA1 function.. Authors - Myung Jong Kim. View ... Acid ceramidase of macrophages traps herpes simplex virus in multivesicular bodies and protects from severe disease.. Authors ... AC, Acid ceramidase, Acylsphingosine deacylase, ASAH, ASAH1, HSD 33, PHP, PHP32, Putative 32 kDa heart protein ...
In vivo delivery of human acid ceramidase via cord blood transplantation and direct injection of lentivirus as novel treatment ... Lysosomal acid alpha-glucosidase consists of four different peptides processed from a single chain precursor. J Biol Chem. 2005 ... Lysosomal Acid Lipase Deficiency: Therapeutic Options. Drug Des Devel Ther. 2020. 14:591-601. [QxMD MEDLINE Link]. ... Acid sphingomyelinase deficiency: prevalence and characterization of an intermediate phenotype of Niemann-Pick disease. J ...
Among the novel biomarkers predictive of resistance, acid ceramidase was one of the latest factors identified in the ...
Acid ceramidase C. *Neutral ceramidases C. *Alkaline ceramidases C. *Ceramide kinase C ...
... : acid ceramidase. Green arrows indicate "is_a"; Purple arrows ... ceramidase activity. Asah1. IDA. color key. Other mouse members of PIRSF017632 with no experimental molecular function ...
Acid ceramidase (ACDase) -mangel er et spektrum af forstyrrelser, der inkluderer en sjælden lysosomal opbevaringsforstyrrelse ... Acid ceramidase (ACDase) -mangel er et spektrum af forstyrrelser, der inkluderer en sjælden lysosomal opbevaringsforstyrrelse ... Syre ceramidase og ceramider. Syre ceramidase (ACDase) (EC # 3.5.1.23) blev først identificeret i 1963 af Gatt i ... Video: Syre Ceramidase Mangel: Farber Sygdom Og SMA-PME. Video: Сенаторы, губернаторы, бизнесмены, философ-социалист (интервью ...
Schematic of the acid ceramidase protein with indications of the corresponding numbers of mutations for each part. Annotations ... Acid ceramidase deficiency: Farber disease and SMA-PME. Orphanet J Rare Dis 2018;13(1):121. Creative Commons Attribution 4.0 ...
Acid ceramidase. ASAH1. Q13510 Homeodomain-interacting protein kinase 1. HIPK1. Q86Z02 Peroxisome proliferator-activated ... Palmitic acid is the first fatty acid produced during fatty acid synthesis and is the precursor to longer fatty acids. As a ... Palmitic acid, or hexadecanoic acid, is one of the most common saturated fatty acids found in animals, plants, and ... The word "napalm" is derived from the word’s naphthenic acid and palmitic acid. Palmitic acid is also used in the ...
... and acid ceramidase activities in cutaneous aging. Experimental dermatology. Aug 2005;14(8):609-618. ... such as glycolic and lactic acids), trichloroacetic acid, beta-hydroxy acids, and others (Hassan 2013). ... Pantothenic acid. Also known as vitamin B5, pantothenic acid is an essential nutrient in the diet and is important to wound ... Omega-3 fatty acids. Omega-3 fatty acids help protect skin against the damaging effects of UV light. Results from preclinical ...
Acid ceramidase is upregulated in AML and represents a novel therapeutic target. ... Acid ceramidase is upregulated in AML and represents a novel therapeutic target ... The increased expression of fatty acid-binding protein 9 in prostate cancer and its prognostic significance. ... The increased expression of fatty acid-binding protein 9 in prostate cancer and its prognostic significance ...
ASAH1, AC, ACDase, Acid ceramidase, ASAH, FLJ21558, FLJ22079, N-acylsphingosine amidohydrolase, PHP, PHP32, Putative 32 kd ...
Ikegami,Inhibition of acid ceramidase elicits mitochondrial dysfunction and oxidative stress in pancreatic cancer cells, ... Q. Guo, I. Kawahata, A. Cheng, H. Wang, W. Jia, H. Yoshino and K. Fukunaga,Fatty acid-binding proteins 3 and 5 are involved in ... I. Kawahata, L. Luc Bousset, R. Melki and K. Fukunaga , Fatty Acid-Binding Protein 3 is Critical for α-Synuclein Uptake and ... Y. Wang, Y. Shinoda, A. Cheng, I. Kawahata and K. Fukunaga,Epidermal fatty acid-binding protein 5 (FABP5) Involvement in alpha ...
... acid ceramidase) an arginine is the general base. Cysteine peptidases can be grouped into fourteen different clans, with ... 2017) Nucleic Acids Res doi: 10.1093/nar/gkx922. Letunic et al. (2020) Nucleic Acids Res doi: 10.1093/nar/gkaa937 ... They are inhibited by thiol chelators such as iodoacetate, iodoacetic acid, N -ethylmaleimide or p -chloromercuribenzoate. ... usually asparagine or aspartic acid, to orientate and activate the imidazolium ring. In only one family of cysteine peptidases ...
Recombinant Mouse Acid ceramidase Protein, His-SUMO, Invitro-E.coli-100ug. QP8262-iv-100ug EnQuireBio 100ug. ... An approach to correlate tandem mass spectral data of peptides with amino acid sequences in a protein database. ... An approach to correlate tandem mass spectral data of peptides with amino acid sequences in a protein database. ...
Acid ceramidase. ASAH1. Q13510 Putative neutral ceramidase C. ASAH2C. P0C7U2 Alkaline ceramidase 2. ACER2. Q5QJU3 ...
Acid ceramidase. ASAH1. Q13510 Putative neutral ceramidase C. ASAH2C. P0C7U2 Alkaline ceramidase 2. ACER2. Q5QJU3 ...
Purchase Recombinant Saccharomyces cerevisiae Alkaline ceramidase YDC1 (YDC1). It is produced in in vitro E.coli expression ... Very low reverse hydrolysis activity, catalyzing synthesis of dihydroceramide from fatty acid and dihydrosphingosine. Is not ... Recombinant Saccharomyces cerevisiae Alkaline ceramidase YDC1 (YDC1). Recombinant Saccharomyces cerevisiae Alkaline ceramidase ... Recombinant Saccharomyces cerevisiae Alkaline ceramidase YDC1 (YDC1), partial ( Yeast-CSB-YP312558SVG1 E.coli-CSB-EP312558SVG1 ...
Reaction schema of the hydrolysis of ceramide by acid ceramidase into sphingosine and free fatty acid ... Acid ceramidase deficiency: Farber disease and SMA-PME. Orphanet J Rare Dis 2018;13(1):121. Creative Commons Attribution 4.0 ...
... they travel to lysosomes where acid ceramidase breaks them down into a fat called sphingosine and a fatty acid. These two ... The reduction in acid ceramidase activity associated with SMA-PME is less than what occurs in another condition called Farber ... The ASAH1 gene mutations that cause SMA-PME result in a reduction of acid ceramidase activity to a level less than one-third of ... The decrease in acid ceramidase activity leads to inefficient breakdown of ceramides and impaired production of its breakdown ...
Johnsons project is entitled Mechanisms and In Vivo Efficacy of Synergistic Acid Ceramidase and Bcl-2 Inhibition in Acute ...
Role of Acid Ceramidase in Inflamation. [Co-PI: Espaillat, Mel Pilar]. Parnia, Dr. Sam. Pulmonary, Critical Care and Sleep ... Joseph V. Bonventre Research Scholar Grant: Transcriptional Regulation of Proximal Tubular Amino Acid Metabolism in AKI. ... KLF-15 Mediates the Renal Protective Effects of Retinoic Acid and Glucocorticoids in Glomerular Kidney Disease ...
Rabbit anti Human Acid Ceramidase 1. Antigen Immunoaffinity Purified Polyclonal. X2712P. Rabbit anti Human Calcium Channel. ...
HUMAN N-ACYLETHANOLAMINE-HYDROLYZING ACID AMIDASE (NAAA) IN COMPLEX WITH NON-COVALENT BENZOTHIAZOLE-PIPERAZINE INHIBITOR ... Nucl Acids Res (1 July 2015) 43 (W1): W576-W579 first published online April 29, 2015. doi:10.1093/nar/gkv402 ... HUMAN N-ACYLETHANOLAMINE-HYDROLYZING ACID AMIDASE (NAAA) IN COMPLEX WITH NON-COVALENT BENZOTHIAZOLE-PIPERAZINE INHIBITOR ... HUMAN N-ACYLETHANOLAMINE-HYDROLYZING ACID AMIDASE (NAAA) IN COMPLEX WITH NON-COVALENT BENZOTHIAZOLE-PIPERAZINE INHIBITOR ...
  • 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)
  • The ASAH1 gene mutations that cause SMA-PME result in a reduction of acid ceramidase activity to a level less than one-third of normal. (encyclopedia.pub)
  • 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)
  • Enhancing ceramide degradation also endows these metabolic benefits, and adiponectin exerts their antidiabetic, cardioprotective, and insulin-sensitizing actions through activating its receptors, which are ligand-activated ceramidases ( 23 ). (frontiersin.org)
  • [ 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)
  • Ceramidase (CDase) hydrolyses the N-acyl linkage of the sphingolipid ceramide. (tno.nl)
  • Farber's disease (lysosomal acid ceramidase deficiency). (bmj.com)
  • 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)
  • Acid ceramidase deficiency: Farber disease and SMA-PME. (medlink.com)
  • Further, activities of acid sphingomyelinase (ASM), acid ceramidase, and sphingosine kinase were measured by ultraperformance liquid chromatography. (uni-potsdam.de)
  • Farber disease (acid ceramidase deficien. (deu.edu.tr)
  • Acid ceramidase (ACDase) -mangel er et spektrum af forstyrrelser, der inkluderer en sjælden lysosomal opbevaringsforstyrrelse kaldet Farber sygdom (FD) og en sjælden epileptisk lidelse kaldet spinal muskelatrofi med progressiv myoklonisk epilepsi (SMA-PME). (biomedicalhouse.com)
  • Farber offentliggjorde senere en sagsrekke med tre patienter i 1952, som en transaktion for det 62. (biomedicalhouse.com)
  • Selvom Farber påviste en stigning i lipider i sine tidlige biokemiske undersøgelser, blev det vigtigste lipid, der ophobes ved Farber sygdom (FD), dvs. (biomedicalhouse.com)
  • Most of the mutations associated with Farber lipogranulomatosis change a single protein building block (amino acid) in acid ceramidase, which severely reduces the activity of the enzyme, typically to less than one-tenth of normal. (encyclopedia.pub)
  • The reduction in acid ceramidase activity associated with SMA-PME is less than what occurs in another condition called Farber lipogranulomatosis (described above). (encyclopedia.pub)
  • Acid ceramidase breaks down fats called ceramides into a fat called sphingosine and a fatty acid. (medlineplus.gov)
  • These are ceramides bearing a long chain fatty acid. (foodb.ca)
  • Within lysosomes, acid ceramidase breaks down fats called ceramides. (encyclopedia.pub)
  • When ceramides need to be replaced, they travel to lysosomes where acid ceramidase breaks them down into a fat called sphingosine and a fatty acid. (encyclopedia.pub)
  • The decrease in acid ceramidase activity leads to inefficient breakdown of ceramides and impaired production of its breakdown products sphingosine and fatty acids. (encyclopedia.pub)
  • The increase in ceramides and reduction in sphingosine and fatty acids likely play a role in the development of the features of SMA-PME, but the exact mechanism is unknown. (encyclopedia.pub)
  • Ceramidase (CDase) hydrolyzes the amide bond in ceramides to yield free fatty acid and sphingosine. (tno.nl)
  • Palmitic acid, also known as palmitate or C16, belongs to the class of organic compounds known as long-chain fatty acids. (foodb.ca)
  • These are fatty acids with an aliphatic tail that contains between 13 and 21 carbon atoms. (foodb.ca)
  • Palmitic acid, or hexadecanoic acid, is one of the most common saturated fatty acids found in animals, plants, and microorganisms. (foodb.ca)
  • Palmitic acid is the first fatty acid produced during fatty acid synthesis and is the precursor to longer fatty acids. (foodb.ca)
  • Mechanisms Involved in the Cytotoxic and Cytoprotective Actions of Saturated Versus Monounsaturated Long-Chain Fatty Acids in Pancreatic Beta-Cells. (medchemexpress.com)
  • In LSDs, there may be a defect that negatively affects that chopping process or makes the lysosome less efficient, and so these fats accumulate and are then converted to more toxic lysosphingolipids by the enzyme acid ceramidase (AC). (fundforcures.org.uk)
  • Quantitative Proteome Analysis of Mouse Liver Lysosomes Provides Evidence for Mannose 6-phosphate-independent Targeting Mechanisms of Acid Hydrolases in Mucolipidosis II. (uni-bielefeld.de)
  • Schematic of the acid ceramidase protein with indications of the corresponding numbers of mutations for each part. (medlink.com)
  • OMIM # 228000), også kendt som Farbers lipogranulomatosis, er en ultralystøs lysosomal opbevaringsforstyrrelse (LSD). (biomedicalhouse.com)
  • Nylige studier har fremhævet mulige biomarkører for en effektiv diagnose af ACDase-mangel. (biomedicalhouse.com)
  • Syre ceramidase (ACDase), der først blev oprenset i 1963, katalyserer syntesen og nedbrydningen af ceramid til sphingosin og fedtsyre (4). (biomedicalhouse.com)
  • I 1972 konstaterede Sugita og kolleger, at ACDase-aktivitet ikke var påviselig i post-mortem-væv fra en FD-patient (5). (biomedicalhouse.com)
  • OXPHOS can be sustained by amino acid (AA) metabolism in AML LSC, with cysteine and glutamine being two of the most important AAs involved in the process [ 10 ] . (encyclopedia.pub)
  • The CDase gene encodes a 670 amino acid. (tno.nl)
  • Inhibitory effect of Porphyromonas gingivalis-derived phosphoethanolamine dihydroceramide on acid ceramidase expression in oral squamous cells. (bvsalud.org)
  • Very low reverse hydrolysis activity, catalyzing synthesis of dihydroceramide from fatty acid and dihydrosphingosine. (cusabio.com)
  • Injectable hyaluronic acid or topical tretinoin (Retin-A) are also commonly used. (lifeextension.com)
  • Hyaluronic acid (HA) has been utilized for a variety of regenerative medical procedures due to its widespread presence in connective tissue and perceived biocompatibility. (globaltechbiz.com)
  • Palmitic acid is a very hydrophobic molecule, practically insoluble in water and relatively neutral. (foodb.ca)
  • Hydrolysis involves usually a catalytic triad consisting of the thiol group of the cysteine, the imidazolium ring of a histidine, and a third residue, usually asparagine or aspartic acid, to orientate and activate the imidazolium ring. (embl.de)
  • In only one family of cysteine peptidases, is the role of the general base assigned to a residue other than a histidine: in peptidases from family C89 (acid ceramidase) an arginine is the general base. (embl.de)
  • It is unclear whether the level of acid ceramidase activity is related to the severity of the disorder. (medlineplus.gov)
  • In humans and other mammals, excess carbohydrates in the body are converted to palmitic acid. (foodb.ca)
  • The lack of myelin resulting from the lack of acid ceramidase breakdown leads to nerve cell dysfunction. (wikipedia.org)
  • In patients with SMA-PME, the ceramidase function decreases to 33.33% effective. (wikipedia.org)
  • ceramid, ikke identificeret før 1967, da det blev isoleret fra en biopsi af en patients nyre (3). (biomedicalhouse.com)
  • the fatty acid component is then used to produce myelin. (wikipedia.org)
  • As a consequence, palmitic acid is a major lipid component of animals. (foodb.ca)
  • Wild-type p53 itself acts by regulating and promoting the tricarboxylic acid (TCA) cycle, for instance by enhancing cytochrome c oxidase assembly (SCO2) expression to maintain cytochrome c oxidase complex and increasing Parkin levels in cells, which increases pyruvate dehydrogenase E1α1 (PDHA1), a critical component of the pyruvate dehydrogenase complex [ 11 ] . (encyclopedia.pub)
  • Palmitic acid is used to produce soaps, cosmetics, and industrial mould release agents. (foodb.ca)
  • Aluminium salts of palmitic acid and naphthenic acid were combined during World War II to produce napalm. (foodb.ca)
  • the fatty acid component is then used to produce myelin. (wikipedia.org)
  • Acid ceramidase breaks down fats called ceramides into a fat called sphingosine and a fatty acid. (medlineplus.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)
  • In the majority of organisms, fatty acid degradation occurs mostly through the beta-oxidation cycle. (smpdb.ca)
  • 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)
  • 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)
  • 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)
  • 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)
  • It is most common fatty acid oxidation disorder and is under the category of inborn error of metabolism. (epainassist.com)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 1997 Nucleic acids Res. (lbl.gov)
  • The intracellular composition of fatty acids (FAs) after BETi treatment reflected a significant reduction in neutral lipids. (biomedcentral.com)
  • 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)
  • 2004) suggested to use 3-(CR)-2-Carboxypiperazin-4-yl-propyl-1-phosphonic-acid (D-CPP), an MLN8054 IC50 NMDA channel blocker. (baxkyardgardener.com)
  • E2 binds to the protein acid ceramidase, which sets off a chain of cellular processes that suppress angiogenesis. (yonsei.ac.kr)
  • 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)
  • 3. Acid ceramidase upregulation in prostate cancer cells confers resistance to radiation: AC inhibition, a potential radiosensitizer. (nih.gov)
  • 4. Novel off-target effect of tamoxifen--inhibition of acid ceramidase activity in cancer cells. (nih.gov)
  • 17. Genetic and pharmacological inhibition of acid ceramidase prevents asymmetric cell division by neosis. (nih.gov)
  • 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)
  • Further, the accumulation of fatty acids accumulates in the liver cells leading to liver disorders. (epainassist.com)
  • 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)
  • The gluconeogenesis is the process of synthesizing glucose from non-carbohydrate sources such as fats and amino acids. (epainassist.com)
  • 12. Targeting acid ceramidase sensitises head and neck cancer to cisplatin. (nih.gov)
  • Inhibitory effect of Porphyromonas gingivalis-derived phosphoethanolamine dihydroceramide on acid ceramidase expression in oral squamous cells. (bvsalud.org)
  • 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)
  • 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)
  • a) The promoter and coding regions of the glutamic acid decarboxylase (GAD) T\cell receptor (TCR) lentivector are depicted to scale. (neuroart2006.com)
  • At the same time, the mitochondria are enriched with fatty acids. (biomedcentral.com)
  • 13. Increased acid ceramidase expression depends on upregulation of androgen-dependent deubiquitinases, USP2, in a human prostate cancer cell line, LNCaP. (nih.gov)
  • 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)
  • 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)
  • 15. Potential role of acid ceramidase in conversion of cytostatic to cytotoxic end-point in pancreatic cancer cells. (nih.gov)
  • Acid ceramidase and human disease. (nih.gov)
  • 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)
  • 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)
  • 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)
  • Further, the blockage of gluconeogenesis and the conversion of medium chain fatty acids to small chain fatty acids cause the reduction of ketones, leading to the hypoketotic condition. (epainassist.com)