Rancidification is the process of complete or incomplete autoxidation or hydrolysis of fats and oils when exposed to air, light, moisture, or bacterial action, producing short-chain aldehydes, ketones and free fatty acids.
An unsaturated fat is a fat or fatty acid in which there is at least one double bond within the fatty acid chain. A fatty acid chain is monounsaturated if it contains one double bond, and polyunsaturated if it contains more than one double bond.
Lipid peroxidation is the conversion of lipids to peroxide and hydroperoxide derivatives. These derivatives, known as lipid peroxides or lipid oxidation products (LOPs), are susceptible to further reactions that are relevant to "DNA and protein modification, radiation damage, aging..." Lipid peroxidation mainly applies to unsaturated fats, especially polyunsaturated fats such as those derived from linoleic acid.
4-Hydroxynonenal, or 4-hydroxy-2-nonenal or 4-HNE or HNE,, is an α,β-unsaturated hydroxyalkenal that is produced by lipid peroxidation in cells. 4-HNE is the primary α,β-unsaturated hydroxyalkenal formed in this process. It is a colorless oil. It is found throughout animal tissues, and in higher quantities during oxidative stress due to the increase in the lipid peroxidation chain reaction, due to the increase in stress events. 4-HNE has been hypothesized to play a key role in cell signal transduction, in a variety of pathways from cell cycle events to cellular adhesion.
Autoxidation refers to oxidations brought about by reactions with oxygen at normal temperatures, without the intervention of flame or electric spark. The term is usually used to describe the gradual degradation of organic compounds in air at ambient temperatures. Many common phenomena can be attributed to autoxidation, such as food going rancid, the 'drying' of varnishes and paints, and the perishing of rubber. It is also an important concept in both industrial chemistry and biology. Autoxidation is therefore a fairly broad term and can encompass examples of photooxygenation and catalytic oxidation.
Docosatetraenoic acid designates any straight chain 22:4 fatty acid.
The isoprostanes are prostaglandin-like compounds formed in vivo from the free radical-catalyzed peroxidation of essential fatty acids without the direct action of cyclooxygenase (COX) enzymes. The compounds were discovered in 1990 by L. Jackson Roberts and Jason D. Morrow in the Division of Clinical Pharmacology at Vanderbilt University. These nonclassical eicosanoids possess potent biological activity as inflammatory mediators that augment the perception of pain. These compounds are accurate markers of lipid peroxidation in both animal and human models of oxidative stress.
Thiobarbituric acid reactive substances (TBARS) are formed as a byproduct of lipid peroxidation which can be detected by the TBARS assay using thiobarbituric acid as a reagent. TBARS can be upregulated, for example, by heart attack or by certain kinds of stroke.
Cyclooxygenase 1 (COX-1), also known as prostaglandin-endoperoxide synthase 1, is an enzyme that in humans is encoded by the PTGS1 gene. In humans it is one of two cyclooxygenases.
Aldehyde dehydrogenase, dimeric NADP-preferring is an enzyme that in humans is encoded by the ALDH3A1 gene.
Oxylipins constitute a family of oxygenated natural products which are formed from fatty acids by pathways involving at least one step of dioxygen-dependent oxidation. Oxylipins are derived from polyunsaturated fatty acids (PUFAs) by COX enzymes (cyclooxygenases), by LOX enzymes (lipoxygenases), or by cytochrome P450 epoxygenase.
Protectin D1 also known as neuroprotectin D1 and abbreviated most commonly as PD1 or NPD1 is a member of the class of specialized proresolving mediators. Like other members of this class of polyunsaturated fatty acid metabolites, it possesses strong anti-inflammatory, anti-apoptotic and neuroprotective activity. PD1 is an aliphatic acyclic alkene 22 carbons in length with two hydroxyl groups at the 10 and 17 carbon positions and one carboxylic acid group at the one carbon position.
12-Hydroxyheptadecatrienoic acid (also termed 12-HHT, 12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid, or 12(S)-HHTrE) is a 17 carbon metabolite of the 20 carbon polyunsaturated fatty acid, arachidonic acid. It was discovered and structurally defined in 1973 by P. Wlodawer, Bengt I. Samuelsson, and M. Hamberg, as a product of arachidonic acid metabolism made by microsomes (i.e. endoplasmic reticulum) isolated from sheep seminal vesicle glands and by intact human platelets. 12-HHT is less ambiguously termed 12-(S)-hydroxy-5Z,8E,10E-heptadecatrienoic acid to indicate the S stereoisomerism of its 12-hydroxyl residue and the Z, E, and E cis-trans isomerism of its three double bonds. The metabolite was for many years thought to be merely a biologically inactive byproduct of prostaglandin synthesis. More recent studies, however, have attached potentially important activity to it.
9-Hydroxyoctadecadienoic acid (or 9-HODE) has been used in the literature to designate either or both of two stereoisomer metabolites of the essential fatty acid, linoleic acid: 9(S)-hydroxy-10(E),12(Z)-octadecadienoic acid (9(S)-HODE) and 9(R)-hydroxy-10(E),12(Z)-octadecadienoic acid (9(R)-HODE); these two metabolites differ in having their hydroxy residues in the S or R configurations, respectively. The accompanying figure gives the structure for 9(S)-HETE. Two other 9-hydroxy linoleic acid derivatives occur in nature, the 10E,12E isomers of 9(S)-HODE and 9(R)-HODE viz., 9(S)-hydroxy-10E,12E-octadecadienoic acid (9(S)-EE-HODE) and 9(R)-hydroxy-10E,12E-octadecadienoic acid (13(R)-EE-HODE); these two derivatives have their double bond at carbon 12 in the E or trans configuration as opposed to the Z or cis configuration. The four 9-HODE isomers, particularly under conditions of oxidative stress, may form together in cells and tissues; they have overlapping but not identical biological activities and significances. Because many studies have not distinguished between the S and R stereoisomers and, particularly in identifying tissue levels, the two EE isomers, 9-HODE is used here when the isomer studied is unclear.
Coronaric acid (isoleukotoxin) is a mono-unsaturated, epoxide derivative of the di-saturated fatty acid, linoleic acid (i.e. 9(Z),12(Z) octadecadienoic acid). It is a mixture of the two optically active isomers of 12(Z) 9,10-epoxy-octadecenoic acid. This mixture is also termed 9,10-epoxy-12Z-octadecenoic acid or 9(10)-EpOME and when formed by or studied in mammalians, isoleukotoxin.
Di-deuterated ethyl linoleate is an experimental, orally-bioavailable synthetic deuterated polyunsaturated fatty acid (PUFA), a part of reinforced lipids. It is an isotopologue of linoleic acid, an essential omega-6 PUFA. The deuterated compound, while identical to natural linoleic acid except for the presence of deuterium, is resistant to lipid peroxidation which makes studies of its cell-protective properties worthwhile.
Retrotope, Inc. is a drug development company advancing the idea that polyunsaturated fatty acids (PUFA) drugs fortified with heavy isotopes protect living cells by making bonds within the delicate molecules inside and around cells harder to break. This makes the cells less prone to damage caused by reactive oxygen species (ROS), one of the principal causes of ageing and age-associated diseases. Founded in 2006 by entrepreneurs and scientists with seed funding from private investors, Retrotope is developing a non-antioxidant approach to preventing lipid peroxidation, a detrimental factor in mitochondrial, neuronal, and retinal diseases. The company employs the virtual business model and works in scientific collaboration with more than 80 research groups in universities worldwide.
Reactive aldehyde species (RASP), also known as reactive aldehydes, refer to a class of electrophilic organic aldehyde molecules that are generally toxic or facilitate inflammation. RASP covalently react with amine groups and thiol groups, particularly in proteins. Following threshold amounts of binding to the electrophile-responsive proteome, RASP modify protein function, as has been described with MAP kinase, protein kinase C, and other proteins that potentiate cytokine release and other aspects of inflammation. Binding of RASP to proteins can also lead to NF-kB activation, autoantibody formation, inflammasome activation, and activation of Scavenger Receptor A. RASP are formed via a variety of processes, including oxidation of alcohols, polyamine metabolism and lipid peroxidation. In addition to binding to proteins and other amine or thiol-containing molecules such as glutathione, RASP are metabolized by aldehyde dehydrogenases or aldehyde reductases. Due to the toxicity of RASP, only a small number of genetic mutations in aldehyde dehydrogenases allow for viable offspring, resulting in Sjögren-Larsson Syndrome, Succinic Semi-Aldehyde Dehydrogenase Deficiency, and other rare diseases.
Isotope effect is observed when molecules containing heavier isotopes of the same atoms are engaged in a chemical reaction at a slower rate. Deuterium-reinforced lipids can be used for the protection of living cells by slowing the chain reaction of lipid peroxidation. The lipid bilayer of the cell and organelle membranes contain polyunsaturated fatty acids (PUFA) are key components of cell and organelle membranes. Any process that either increases oxidation of PUFAs or hinders their ability to be replaced can lead to serious disease. Correspondingly, drugs that stop the chain reaction of lipid peroxidation have preventive and therapeutic potential.
Reinforced lipids are lipid molecules in which some of the fatty acids contain deuterium instead of hydrogen. They can be used for the protection of living cells by slowing the chain reaction due to isotope effect on lipid peroxidation. The lipid bilayer of the cell and organelle membranes contain polyunsaturated fatty acids (PUFA) are key components of cell and organelle membranes. Any process that either increases oxidation of PUFAs or hinders their ability to be replaced can lead to serious disease. Correspondingly, use of reinforced lipids that stop the chain reaction of lipid peroxidation has preventive and therapeutic potential.
