Lipids are a broad group of organic compounds which include fats, waxes, sterols, fat-soluble vitamins, monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include storing energy, signaling, and acting as structural components of cell membranes. Lipids have applications in the cosmetic and food industries, and in nanotechnology.
In biochemistry, a kinase is an enzyme that catalyzes the transfer of phosphate groups from high-energy, phosphate-donating molecules to specific substrates. This process is known as phosphorylation, where the high-energy ATP molecule donates a phosphate group to the substrate molecule. As a result, kinase produces a phosphorylated substrate and ADP. Conversely, it is referred to as dephosphorylation when the phosphorylated substrate donates a phosphate group and ADP gains a phosphate group. These two processes, phosphorylation and dephosphorylation, occur four times during glycolysis.
Sphingolipids are a class of lipids containing a backbone of sphingoid bases, which are a set of aliphatic amino alcohols that includes sphingosine. They were discovered in brain extracts in the 1870s and were named after the mythological sphinx because of their enigmatic nature. These compounds play important roles in signal transduction and cell recognition. Sphingolipidoses, or disorders of sphingolipid metabolism, have particular impact on neural tissue. A sphingolipid with a terminal hydroxyl group is a ceramide. Other common groups bonded to the terminal oxygen atom include phosphocholine, yielding a sphingomyelin, and various sugar monomers or dimers, yielding cerebrosides and globosides, respectively. Cerebrosides and globosides are collectively known as glycosphingolipids.
In molecular biology, biosynthesis is a multi-step, enzyme-catalyzed process where substrates are converted into more complex products in living organisms. In biosynthesis, simple compounds are modified, converted into other compounds, or joined to form macromolecules. This process often consists of metabolic pathways. Some of these biosynthetic pathways are located within a single cellular organelle, while others involve enzymes that are located within multiple cellular organelles. Examples of these biosynthetic pathways include the production of lipid membrane components and nucleotides. Biosynthesis is usually synonymous with anabolism.
Sphingomyelin is a type of sphingolipid found in animal cell membranes, especially in the membranous myelin sheath that surrounds some nerve cell axons. It usually consists of phosphocholine and ceramide, or a phosphoethanolamine head group; therefore, sphingomyelins can also be classified as sphingophospholipids. In humans, SPH represents ~85% of all sphingolipids, and typically make up 10–20 mol % of plasma membrane lipids.
Glycosphingolipids are a subtype of glycolipids containing the amino alcohol sphingosine. They may be considered as sphingolipids with an attached carbohydrate. Glycosphingolipids are a group of lipids and are a part of the cell membrane. They consist of a hydrophobic ceramide part and a glycosidically bound carbohydrate part. This oligosaccharide content remains on the outside of the cell membrane where it is important for biological processes such as cell adhesion or cell–cell interactions. Glycosphingolipids play also important role in oncogenesis and ontogenesis.
Fumonisin B1 is the most prevalent member of a family of toxins, known as fumonisins, produced by multiple species of Fusarium molds, such as Fusarium verticillioides, which occur mainly in maize (corn), wheat and other cereals. Fumonisin B1 contamination of maize has been reported worldwide at mg/kg levels. Human exposure occurs at levels of micrograms to milligrams per day and is greatest in regions where maize products are the dietary staple.
Ceramides are a family of waxy lipid molecules. A ceramide is composed of sphingosine and a fatty acid joined by an amide bond. Ceramides are found in high concentrations within the cell membrane of eukaryotic cells, since they are component lipids that make up sphingomyelin, one of the major lipids in the lipid bilayer. Contrary to previous assumptions that ceramides and other sphingolipids found in cell membrane were purely supporting structural elements, ceramide can participate in a variety of cellular signaling: examples include regulating differentiation, proliferation, and programmed cell death (PCD) of cells.
Sphingosine kinase (SphK) is a conserved lipid kinase that catalyzes formation sphingosine-1-phosphate (S1P) from the precursor sphingolipid sphingosine. Sphingolipid metabolites, such as ceramide, sphingosine and sphingosine-1-phosphate, are lipid second messengers involved in diverse cellular processes. There are two forms of SphK, SphK1 and SphK2. SphK1 is found in the cytosol of eukaryotic cells, and migrates to the plasma membrane upon activation. SphK2 is localized to the nucleus.
Lipid signaling, broadly defined, refers to any biological cell signaling event involving a lipid messenger that binds a protein target, such as a receptor, kinase or phosphatase, which in turn mediate the effects of these lipids on specific cellular responses. Lipid signaling is thought to be qualitatively different from other classical signaling paradigms because lipids can freely diffuse through membranes. One consequence of this is that lipid messengers cannot be stored in vesicles prior to release and so are often biosynthesized "on demand" at their intended site of action. As such, many lipid signaling molecules cannot circulate freely in solution but, rather, exist bound to special carrier proteins in serum.
Sphingosine-1-phosphate (S1P) is a signaling sphingolipid, also known as lysosphingolipid. It is also referred to as a bioactive lipid mediator. Sphingolipids at large form a class of lipids characterized by a particular aliphatic aminoalcohol, which is sphingosine.
Ceramidase is an enzyme which cleaves fatty acids from ceramide, producing sphingosine (SPH) which in turn is phosphorylated by a sphingosine kinase to form sphingosine-1-phosphate (S1P).
Sphingosine-1-phosphate receptor 1, also known as endothelial differentiation gene 1 (EDG1) is a protein that in humans is encoded by the S1PR1 gene. S1PR1 is a G-protein-coupled receptor which binds the bioactive signaling molecule sphingosine 1-phosphate (S1P). S1PR1 belongs to a sphingosine-1-phosphate receptor subfamily comprising five members (S1PR1-5). S1PR1 was originally identified as an abundant transcript in endothelial cells and it has an important role in regulating endothelial cell cytoskeletal structure, migration, capillary-like network formation and vascular maturation. In addition, S1PR1 signaling is important in the regulation of lymphocyte maturation, migration and trafficking.
The enzyme phosphatidate phosphatase (PAP, EC 3.1.3.4) is a key regulatory enzyme in lipid metabolism, catalyzing the conversion of phosphatidate to diacylglycerol:
In enzymology, sphingosine N-acyltransferases (ceramide synthases (CerS), EC 2.3.1.24) are enzymes that catalyze the chemical reaction of synthesis of ceramide:
In enzymology, a ceramide kinase, also abbreviated as CERK, is an enzyme that catalyzes the chemical reaction:
Collagen type IV alpha-3-binding protein, also known as ceramide transfer protein (CERT) or StAR-related lipid transfer protein 11 (STARD11) is a protein that in humans is encoded by the COL4A3BP gene. The protein contains a pleckstrin homology domain at its amino terminus and a START domain towards the end of the molecule. It is a member of the StarD2 subfamily of START domain proteins.
Serine palmitoyltransferase, long chain base subunit 2, also known as SPTLC2, is a protein which in humans is encoded by the SPTLC2 gene. SPTLC2 belongs to the class-II pyridoxal-phosphate-dependent aminotransferase family.
Safingol 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. In phase I clinical trials, it was found to be safe to co-administer with cisplatin, but caused reversible dose-dependent hepatotoxicity.
Sarah Spiegel is professor and chair of the Department of Biochemistry and Molecular Biology at Virginia Commonwealth University (VCU). In the mid-1990s she discovered the sphingosine-1-phosphate (S1P) molecule, a lipid which has been identified as a signaler for the spread of cancer, inflammation, and cardiovascular disease. Her research continues to focus on S1P.
