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N-acylsphingosine
Ceramides are a family of waxy lipid molecules. A ceramide is composed of N-acetylsphingosine and a fatty acid. 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. The word ''ceramide'' comes from the Latin ''cera'' (wax) and ''amide''. Ceramide is a component of vernix caseosa, the waxy or cheese-like white substance found coating the skin of newborn human infants. Pathways for ceramide synthesis There are three major pathways of ceramide generation. First, the sphingomyelinase pathway uses an enzyme to break down sphingomyelin in the ...
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De Novo Synthesis
In chemistry, ''de novo'' synthesis () refers to the synthesis of complex molecules from simple molecules such as sugars or amino acids, as opposed to recycling after partial degradation. For example, nucleotides are not needed in the diet as they can be constructed from small precursor molecules such as formate and aspartate. Methionine, on the other hand, is needed in the diet because while it can be degraded to and then regenerated from homocysteine, it cannot be synthesized ''de novo''. Nucleotide ''De novo'' pathways of nucleotides do not use free bases: adenine (abbreviated as A), guanine (G), cytosine (C), thymine (T), or uracil (U). The purine ring is built up one atom or a few atoms at a time and attached to ribose throughout the process. Pyrimidine ring is synthesized as orotate and attached to ribose phosphate and later converted to common pyrimidine nucleotides. Cholesterol Cholesterol is an essential structural component of animal cell membranes. Cholestero ...
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Dihydroceramide Desaturase
Dihydroceramide desaturase is the enzyme involved in the conversion of dihydroceramide into ceramide by inserting the 4,5-''trans''-double bond to the sphingolipid backbone of dihydroceramide. DDase require the and the NAD(P)H as cofactor. The activity of DDase is influenced by several factors as # alkyl chain length of the sphingoid base (in the order C18 > C12 > C8) and fatty acid (C8 > C18) # The stereochemistry Stereochemistry, a subdiscipline of chemistry, involves the study of the relative spatial arrangement of atoms that form the structure of molecules and their manipulation. The study of stereochemistry focuses on the relationships between stereois ... of the sphingoid base (D-erythro- > L-threo-dihydroceramides) # the nature of the headgroup, with the highest activity with dihydroceramide, but some (approximately 20%) activity with dihydroglucosylceramide # The ability to utilize alternative reductants like ascorbic acid could substitute for a reduced pyridine nucl ...
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Dihydrosphingosine
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.Schwartz, G. K., Haimovitz-Friedman, A., Dhupar, S. K., Ehleiter, D., Maslak, P., Lai, L., ... & Albino, A. P. (1995). Potentiation of apoptosis by treatment with the protein kinase C-specific inhibitor safingol in mitomycin C-treated gastric cancer cells. Journal of the National Cancer Institute, 87(18), 1394-1399. 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-admin ...
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Serine Palmitoyl Transferase
In enzymology, a serine C-palmitoyltransferase () is an enzyme that catalyzes the chemical reaction: :palmitoyl-CoA + L-serine \rightleftharpoons CoA + 3-dehydro-D-sphinganine + CO2 Thus, the two substrates of this enzyme are palmitoyl-CoA and L-serine, whereas its 3 products are CoA, 3-dehydro-D-sphinganine, and CO2. This reaction is a key step in the biosynthesis of sphingosine which is a precursor of many other sphingolipids. This enzyme participates in sphingolipid metabolism. It employs one cofactor, pyridoxal phosphate. Nomenclature This enzyme belongs to the family of transferases, specifically those acyltransferases transferring groups other than aminoacyl groups. The systematic name of this enzyme class is palmitoyl-CoA:L-serine C-palmitoyltransferase (decarboxylating). Other names in common use include: * serine palmitoyltransferase, * SPT, 3-oxosphinganine synthetase, and * acyl-CoA:serine C-2 acyltransferase decarboxylating. Structure Serine C ...
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Serine
Serine (symbol Ser or S) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated − form under biological conditions), a carboxyl group (which is in the deprotonated − form under biological conditions), and a side chain consisting of a hydroxymethyl group, classifying it as a polar amino acid. It can be synthesized in the human body under normal physiological circumstances, making it a nonessential amino acid. It is encoded by the codons UCU, UCC, UCA, UCG, AGU and AGC. Occurrence This compound is one of the naturally occurring proteinogenic amino acids. Only the L-stereoisomer appears naturally in proteins. It is not essential to the human diet, since it is synthesized in the body from other metabolites, including glycine. Serine was first obtained from silk protein, a particularly rich source, in 1865 by Emil Cramer. Its name is derived from the Latin for silk, ''sericum''. Serine's structure was estab ...
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Palmitate
Palmitic acid (hexadecanoic acid in IUPAC nomenclature) is a fatty acid with a 16-carbon chain. It is the most common saturated fatty acid found in animals, plants and microorganisms.Gunstone, F. D., John L. Harwood, and Albert J. Dijkstra. The Lipid Handbook, 3rd ed. Boca Raton: CRC Press, 2007. , Its chemical formula is CH3(CH2)14COOH, and its C:D (the total number of carbon atoms to the number of carbon-carbon double-bonds) is 16:0. It is a major component of the oil from the fruit of oil palms (palm oil), making up to 44% of total fats. Meats, cheeses, butter, and other dairy products also contain palmitic acid, amounting to 50–60% of total fats. Palmitates are the salts and esters of palmitic acid. The palmitate anion is the observed form of palmitic acid at physiologic pH (7.4). Occurrence and production Palmitic acid was discovered by Edmond Frémy in 1840, in saponified palm oil. This remains the primary industrial route for its production, with the triglycerides (fat ...
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Apoptosis
Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, DNA fragmentation, and mRNA decay. The average adult human loses between 50 and 70 billion cells each day due to apoptosis. For an average human child between eight and fourteen years old, approximately twenty to thirty billion cells die per day. In contrast to necrosis, which is a form of traumatic cell death that results from acute cellular injury, apoptosis is a highly regulated and controlled process that confers advantages during an organism's life cycle. For example, the separation of fingers and toes in a developing human embryo occurs because cells between the digits undergo apoptosis. Unlike necrosis, apoptosis produces cell fragments called apoptotic ...
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Radiation
In physics, radiation is the emission or transmission of energy in the form of waves or particles through space or through a material medium. This includes: * ''electromagnetic radiation'', such as radio waves, microwaves, infrared, visible light, ultraviolet, x-rays, and gamma radiation (γ) * ''particle radiation'', such as alpha radiation (α), beta radiation (β), proton radiation and neutron radiation (particles of non-zero rest energy) * '' acoustic radiation'', such as ultrasound, sound, and seismic waves (dependent on a physical transmission medium) * ''gravitational wave, gravitational radiation'', that takes the form of gravitational waves, or ripples in the curvature of spacetime Radiation is often categorized as either ''ionizing radiation, ionizing'' or ''non-ionizing radiation, non-ionizing'' depending on the energy of the radiated particles. Ionizing radiation carries more than 10 electron volt, eV, which is enough to ionize atoms and molecules and break ...
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Plasma Membrane
The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (the extracellular space). The cell membrane consists of a lipid bilayer, made up of two layers of phospholipids with cholesterols (a lipid component) interspersed between them, maintaining appropriate membrane fluidity at various temperatures. The membrane also contains membrane proteins, including integral proteins that span the membrane and serve as membrane transporters, and peripheral proteins that loosely attach to the outer (peripheral) side of the cell membrane, acting as enzymes to facilitate interaction with the cell's environment. Glycolipids embedded in the outer lipid layer serve a similar purpose. The cell membrane controls the movement of substances in and out of cells and organelles, being selectively permeable to ions an ...
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Phospholipid
Phospholipids, are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids typically have omega-3 fatty acids EPA and DHA integrated as part of the phospholipid molecule. The phosphate group can be modified with simple organic molecules such as choline, ethanolamine or serine. Phospholipids are a key component of all cell membranes. They can form lipid bilayers because of their amphiphilic characteristic. In eukaryotes, cell membranes also contain another class of lipid, sterol, interspersed among the phospholipids. The combination provides fluidity in two dimensions combined with mechanical strength against rupture. Purified phospholipids are produced commercially and have found applications in nanotechnology and materials science. The first phospholipid identified in 1847 as such in biological tissues was lecith ...
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