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Sphingolipid metabolism overview related metabolites
find 10 related metabolites which is associated with chemical reaction(pathway) Sphingolipid metabolism overview
3-keto-sphinganine ⟶ Sphinganine
Sphinganine
Sphinganine, also known as c18-dihydrosphingosine or safingol, is a member of the class of compounds known as 1,2-aminoalcohols. 1,2-aminoalcohols are organic compounds containing an alkyl chain with an amine group bound to the C1 atom and an alcohol group bound to the C2 atom. Thus, sphinganine is considered to be a sphingoid base lipid molecule. Sphinganine is practically insoluble (in water) and a very weakly acidic compound (based on its pKa). Sphinganine can be found in a number of food items such as agar, biscuit, herbs and spices, and pasta, which makes sphinganine a potential biomarker for the consumption of these food products. Sphinganine can be found primarily in blood, feces, and urine, as well as throughout most human tissues. Sphinganine exists in all eukaryotes, ranging from yeast to humans. In humans, sphinganine is involved in few metabolic pathways, which include globoid cell leukodystrophy, metachromatic leukodystrophy (MLD), and sphingolipid metabolism. Sphinganine is also involved in few metabolic disorders, which include fabry disease, gaucher disease, and krabbe disease. Moreover, sphinganine is found to be associated with pregnancy. Sphinganine is a lyso-sphingolipid protein kinase inhibitor. It has the molecular formula C18H39NO2 and is a colorless solid. Medicinally, safingol has demonstrated promising anticancer potential as a modulator of multi-drug resistance and as an inducer of necrosis. The administration of safingol alone has not been shown to exert a significant effect on tumor cell growth. However, preclinical and clinical studies have shown that combining safingol with conventional chemotherapy agents such as fenretinide, vinblastine, irinotecan and mitomycin C can dramatically potentiate their antitumor effects. Currently in Phase I clinical trials, it is believed to be safe to co-administer with cisplatin . Sphinganine belongs to the class of organic compounds known as 1,2-aminoalcohols. These are organic compounds containing an alkyl chain with an amine group bound to the C1 atom and an alcohol group bound to the C2 atom. Thus, sphinganine is considered to be a sphingoid base lipid molecule. Sphinganine is a very hydrophobic molecule, practically insoluble (in water), and relatively neutral. Sphinganine exists in all living species, ranging from bacteria to humans. Within humans, sphinganine participates in a number of enzymatic reactions. In particular, sphinganine can be converted into 3-dehydrosphinganine through its interaction with the enzyme 3-ketodihydrosphingosine reductase. In addition, sphinganine can be converted into sphinganine 1-phosphate; which is catalyzed by the enzyme sphingosine kinase 2. Outside of the human body, sphinganine has been detected, but not quantified in, several different foods, such as Mexican oregano, jostaberries, winter squash, angelica, and epazotes. This could make sphinganine a potential biomarker for the consumption of these foods. Sphinganine blocks postlysosomal cholesterol transport by inhibiting low-density lipoprotein-induced esterification of cholesterol and causing unesterified cholesterol to accumulate in perinuclear vesicles. It has been suggested that endogenous sphinganine may inhibit cholesterol transport in Niemann-Pick Type C (NPC) disease (PMID: 1817037). D004791 - Enzyme Inhibitors KEIO_ID D078 D-Erythro-dihydrosphingosin directly inhibits cytosolic phospholipase A2α (cPLA2α) activity. D-Erythro-dihydrosphingosin directly inhibits cytosolic phospholipase A2α (cPLA2α) activity.
Sphingosine
Sphingosine, also known as (4E)-sphingenine or sphing-4-enine, belongs to the class of organic compounds known as 1,2-aminoalcohols. These are organic compounds containing an alkyl chain with an amine group bound to the C1 atom and an alcohol group bound to the C2 atom. Sphingosine is an 18-carbon amino alcohol with an unsaturated hydrocarbon chain, which forms a primary part of sphingolipids. Sphingolipids are a class of cell membrane lipids that include sphingomyelin. Thus, sphingosine is considered to be a sphingoid base lipid. Sphingosine is a very hydrophobic molecule, practically insoluble (in water), and relatively neutral. Sphingosine is found in all living organisms ranging from bacteria to plants to humans. Sphingosine is synthesized from palmitoyl CoA and serine in a condensation required to yield dehydrosphingosine. Dehydrosphingosine is then reduced by NADPH to dihydrosphingosine (sphinganine), and finally oxidized by FAD to sphingosine. Within humans and other mammals, sphingosine participates in a number of enzymatic reactions. In particular, sphingosine can be converted into sphingosine 1-phosphate through its interaction with the enzyme sphingosine kinase 2. sphingosine 1-phosphate is an important signaling molecule. In addition, sphingosine can be biosynthesized from sphingosine 1-phosphate; which is mediated by the enzyme sphingosine-1-phosphate phosphatase 2. Sphingosine and its derivative sphinganine are the major bases of the sphingolipids in mammals. In humans, sphingosine is involved in globoid cell leukodystrophy. Cerebrosides is the common name for a group of glycosphingolipids called monoglycosylceramides which are important components in animal muscle and nerve cell membranes. They consist of a ceramide with a single sugar residue at the 1-hydroxyl moiety. The sugar residue can be either glucose or galactose; the two major types are therefore called glucocerebrosides and galactocerebrosides. Galactocerebrosides are typically found in neural tissue, while glucocerebrosides are found in other tissues. Sphingosine. CAS Common Chemistry. CAS, a division of the American Chemical Society, n.d. https://commonchemistry.cas.org/detail?cas_rn=123-78-4 (retrieved 2024-07-16) (CAS RN: 123-78-4). Licensed under the Attribution-Noncommercial 4.0 International License (CC BY-NC 4.0). D-erythro-Sphingosine (Erythrosphingosine) is a very potent activator of p32-kinase with an EC50 of 8 μM, and inhibits protein kinase C (PKC). D-erythro-Sphingosine (Erythrosphingosine) is also a PP2A activator[1][2][3][4]. D-erythro-Sphingosine (Erythrosphingosine) is a very potent activator of p32-kinase with an EC50 of 8 μM, and inhibits protein kinase C (PKC). D-erythro-Sphingosine (Erythrosphingosine) is also a PP2A activator[1][2][3][4].
Sphingosine 1-phosphate
Sphingosine 1-phosphate (S1P), also known as sphing-4-enine-1-phosphate, is classified as a member of the phosphosphingolipids. Phosphosphingolipids are sphingolipids with a structure based on a sphingoid base that is attached to a phosphate head group. They differ from phosphonospingolipids which have a phosphonate head group. S1P is a compound with potent bioactive actions in sphingolipid metabolism, the calcium signalling pathway, and neuroactive ligand-receptor interaction. Generated by sphingosine kinases and ceramide kinase, S1P control numerous aspects of cell physiology, including cell survival and mammalian inflammatory responses. S1P is involved in cyclooxygenase-2 induction (COX-2) and regulates the production of eicosanoids (important inflammatory mediators). S1P functions mainly via G-protein-coupled receptors and probably also has intracellular targets (PMID: 16219683). S1P is considered to be practically insoluble (in water) and acidic. Sphingosine-1-phosphate. CAS Common Chemistry. CAS, a division of the American Chemical Society, n.d. https://commonchemistry.cas.org/detail?cas_rn=26993-30-6 (retrieved 2024-07-15) (CAS RN: 26993-30-6). Licensed under the Attribution-Noncommercial 4.0 International License (CC BY-NC 4.0).
Hexadecenal
Among the 19 human ALDHs, ALDH3A2 is the only known ALDH that catalyzes the oxidation of long-chain fatty aldehydes including C16 aldehydes (hexadecanal and trans-2-hexadecenal) generated through sphingolipid metabolism. (PMID: 23721920) We recently identified that two products within the sphingolipid pathway, sphingosine-1-PO4 and hexadecenal, directly regulate BAK and BAX activation, respectively. (PMID: 23750296) Sphingosine-1-phosphate lyase (SPL) is the only known enzyme that irreversibly cleaves sphingosine-1-phosphate (S1P) into phosphoethanolamine and (2E)-hexadecenal during the final step of sphingolipid catabolism. (PMID: 22444536) Sphingosine 1-phosphate, a bioactive signaling molecule with diverse cellular functions, is irreversibly degraded by the endoplasmic reticulum enzyme sphingosine 1-phosphate lyase, generating trans-2-hexadecenal and phosphoethanolamine. We recently demonstrated that trans-2-hexadecenal causes cytoskeletal reorganization, detachment, and apoptosis in multiple cell types via a JNK-dependent pathway. (PMID: 22727907)
Palmityl-CoA
Palmityl-CoA is a fatty acid coenzyme derivative which plays a key role in fatty acid oxidation and biosynthesis. A fatty acid coenzyme derivative which plays a key role in fatty acid oxidation and biosynthesis. [HMDB] COVID info from WikiPathways Corona-virus Coronavirus SARS-CoV-2 COVID-19 SARS-CoV COVID19 SARS2 SARS
Palmitaldehyde
Palmitaldehyde, also known as 1-hexadecanal, is a member of the class of compounds known as fatty aldehydes. Fatty aldehydes are long chain aldehydes with a chain of at least 12 carbon atoms. Thus, palmitaldehyde is considered to be a fatty aldehyde lipid molecule. Palmitaldehyde is practically insoluble (in water) and an extremely weak acidic compound (based on its pKa). Palmitaldehyde can be found in a number of food items such as rose hip, lambsquarters, pak choy, and swede, which makes palmitaldehyde a potential biomarker for the consumption of these food products. Palmitaldehyde exists in all eukaryotes, ranging from yeast to humans. In humans, palmitaldehyde is involved in few metabolic pathways, which include globoid cell leukodystrophy, metachromatic leukodystrophy (MLD), and sphingolipid metabolism. Palmitaldehyde is also involved in few metabolic disorders, which include fabry disease, gaucher disease, and krabbe disease. Palmitaldehyde is an intermediate in the metabolism of Glycosphingolipid. It is a substrate for Sphingosine-1-phosphate lyase 1. Hexadecanal (Palmitaldehyde) is a free fatty aldehyde present in animals[1]. Hexadecanal (Palmitaldehyde) is a free fatty aldehyde present in animals[1].
Stearoyl-CoA
Stearoyl-CoA is a long-chain acyl CoA ester that acts as an intermediate metabolite in the biosynthesis of monounsaturated fatty acids; a critical committed step in the reaction is the introduction of the cis-configuration double bond into acyl-CoAs (between carbons 9 and 10). This oxidative reaction is catalyzed by the iron-containing, microsomal enzyme, stearoyl-CoA desaturase (SCD, EC 1.14.19.1). NADH supplies the reducing equivalents for the reaction, the flavoprotein is cytochrome b5-reductase and the electron carrier is the heme protein cytochrome b5. Stearoyl-CoA is converted into oleoyl-CoA and then used as a major substrate for the synthesis of various kinds of lipids including phospholipids, triglycerides, cholesteryl esters and wax esters. Oleic acid is the preferred substrate for acyl-CoA cholesterol acyltransferase (ACAT, EC 2.3.1.26) and diacylglycerol acyltransferase (DGAT, EC 2.3.1.20), the enzymes responsible for cholesteryl esters and triglycerides synthesis, respectively. In addition oleate is the major monounsaturated fatty acid in human adipose tissue and in the phospholipid of the red-blood-cell membrane. In the biosynthesis of sphinganine, stearoyl-CoA proceeds through the acyl-CoA + serine -> 3-keto-sphinganine -> sphinganine pathway, with the key enzyme being acyl-CoA serine acyltransferase (EC 2.3.1.50) to yield C20-(3-ketosphinganine) long-chain base. There is growing recognition that acyl-CoA esters could act as signaling molecules in cellular metabolism. (PMID: 12538075, 10998569, Prostaglandins Leukot Essent Fatty Acids. 2003 Feb;68(2):113-21.) [HMDB]. Stearoyl-CoA is found in many foods, some of which are romaine lettuce, grapefruit/pummelo hybrid, radish, and european cranberry. Stearoyl-CoA is a long-chain acyl CoA ester that acts as an intermediate metabolite in the biosynthesis of monounsaturated fatty acids; a critical committed step in the reaction is the introduction of the cis-configuration double bond into acyl-CoAs (between carbons 9 and 10). This oxidative reaction is catalyzed by the iron-containing, microsomal enzyme, stearoyl-CoA desaturase (SCD, EC 1.14.19.1). NADH supplies the reducing equivalents for the reaction, the flavoprotein is cytochrome b5-reductase and the electron carrier is the heme protein cytochrome b5. Stearoyl-CoA is converted into oleoyl-CoA and then used as a major substrate for the synthesis of various kinds of lipids including phospholipids, triglycerides, cholesteryl esters and wax esters. Oleic acid is the preferred substrate for acyl-CoA cholesterol acyltransferase (ACAT, EC 2.3.1.26) and diacylglycerol acyltransferase (DGAT, EC 2.3.1.20), the enzymes responsible for cholesteryl esters and triglycerides synthesis, respectively. In addition oleate is the major monounsaturated fatty acid in human adipose tissue and in the phospholipid of the red-blood-cell membrane. In the biosynthesis of sphinganine, stearoyl-CoA proceeds through the acyl-CoA + serine -> 3-keto-sphinganine -> sphinganine pathway, with the key enzyme being acyl-CoA serine acyltransferase (EC 2.3.1.50) to yield C20-(3-ketosphinganine) long-chain base. There is growing recognition that acyl-CoA esters could act as signaling molecules in cellular metabolism. (PMID: 12538075, 10998569, Prostaglandins Leukot Essent Fatty Acids. 2003 Feb;68(2):113-21.).
Sphinganine 1-phosphate
Sphinganine 1-phosphate is an intermediate in the metabolism of Glycosphingolipids and sphingolipids. It is a substrate for Sphingosine kinase 1, Lipid phosphate phosphohydrolase 2, Sphingosine kinase 2, Sphingosine-1-phosphate lyase 1, Lipid phosphate phosphohydrolase 1 and Lipid phosphate phosphohydrolase 3. [HMDB]. Sphinganine 1-phosphate is found in many foods, some of which are winter squash, chicory roots, star fruit, and butternut squash. Sphinganine 1-phosphate is an intermediate in the metabolism of Glycosphingolipids and sphingolipids. It is a substrate for Sphingosine kinase 1, Lipid phosphate phosphohydrolase 2, Sphingosine kinase 2, Sphingosine-1-phosphate lyase 1, Lipid phosphate phosphohydrolase 1 and Lipid phosphate phosphohydrolase 3.
Eicosanoyl-CoA
Eicosanoyl-CoA is an intermediate metabolite in the synthesis of phosphatidic acid, a substrate of lysophosphatidic acid acyltransferase with high specificity as an acyl donor. Cells and membranes of mammalian cells synthesize their glycerophospholipids and triglycerides to maintain the cellular integrity and to provide energy for cellular functions. The phospholipids are synthesized de novo in cells through an evolutionary conserved process involving serial acylations of glycerol-3-phosphate. Several isoforms of the enzyme 1-acylglycerol-3-phosphate-O-acyltransferase (EC 2.3.1.51, AGPAT) acylate lysophosphatidic acid at the sn-2 position to produce phosphatidic acid. Bile acid-CoA:amino acid N-acyltransferase (EC 2.3.1.65, BACAT) catalyzes the conjugation of bile acids to glycine and taurine for excretion into bile and can utilize Eicosanoyl-CoA as an acyl donor as well; this may play important roles in protection against toxicity by accumulation of unconjugated bile acids and non-esterified very long-chain fatty acids. (PMID: 17535882, 12810727) [HMDB] Eicosanoyl-CoA is an intermediate metabolite in the synthesis of phosphatidic acid, a substrate of lysophosphatidic acid acyltransferase with high specificity as an acyl donor. Cells and membranes of mammalian cells synthesize their glycerophospholipids and triglycerides to maintain the cellular integrity and to provide energy for cellular functions. The phospholipids are synthesized de novo in cells through an evolutionary conserved process involving serial acylations of glycerol-3-phosphate. Several isoforms of the enzyme 1-acylglycerol-3-phosphate-O-acyltransferase (EC 2.3.1.51, AGPAT) acylate lysophosphatidic acid at the sn-2 position to produce phosphatidic acid. Bile acid-CoA:amino acid N-acyltransferase (EC 2.3.1.65, BACAT) catalyzes the conjugation of bile acids to glycine and taurine for excretion into bile and can utilize Eicosanoyl-CoA as an acyl donor as well; this may play important roles in protection against toxicity by accumulation of unconjugated bile acids and non-esterified very long-chain fatty acids. (PMID: 17535882, 12810727).
3-Dehydrosphinganine
3-Dehydrosphinganine is an intermediate in the metabolism of Glycosphingolipids. It is a substrate for Serine palmitoyltransferase 1 and Serine palmitoyltransferase 2. [HMDB]. 3-Dehydrosphinganine is found in many foods, some of which are beech nut, muskmelon, broccoli, and groundcherry. 3-Dehydrosphinganine is an intermediate in the metabolism of Glycosphingolipids. It is a substrate for Serine palmitoyltransferase 1 and Serine palmitoyltransferase 2.
