Deuterium (or hydrogen-2, symbol 2
H
or D, also known as heavy hydrogen) is one of two stable isotopes of hydrogen (the other being protium, or hydrogen-1). The nucleus of a deuterium atom, called a deuteron, contains one proton and one neutron, whereas the far more common protium has no neutrons in the nucleus. Deuterium has a natural abundance in Earth's oceans of about one atom of deuterium among every 6,420 atoms of hydrogen (see heavy water). Thus deuterium accounts for approximately 0.0156% by number (0.0312% by mass) of all the naturally occurring hydrogen in the oceans (i.e 4.85 1013 tonnes of deuterium – mainly in form of HOD and only rarely in form of D2O – in 1.4 1018 tonnes of water), while protium accounts for more than 99.98%. The abundance of deuterium changes slightly from one kind of natural water to another (see Vienna Standard Mean Ocean Water). (Tritium is yet another hydrogen isotope with symbol 3
H
or T. It has two neutrons, and is radioactive and much rarer than deuterium.)
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.
A peroxisome (IPA:[pɛɜˈɹɒksɪˌsoʊm]) is a membrane-bound organelle, a type of microbody, found in the cytoplasm of virtually all eukaryotic cells. Peroxisomes are oxidative organelles. Frequently, molecular oxygen serves as a co-substrate, from which hydrogen peroxide (H2O2) is then formed. Peroxisomes owe their name to hydrogen peroxide generating and scavenging activities. They perform key roles in lipid metabolism and the conversion of reactive oxygen species. Peroxisomes are involved in the catabolism of very long chain fatty acids, branched chain fatty acids, bile acid intermediates (in the liver), D-amino acids, and polyamines, the reduction of reactive oxygen species – specifically hydrogen peroxide – and the biosynthesis of plasmalogens, i.e., ether phospholipids critical for the normal function of mammalian brains and lungs. They also contain approximately 10% of the total activity of two enzymes (Glucose-6-phosphate dehydrogenase and 6-Phosphogluconate dehydrogenase) in the pentose phosphate pathway, which is important for energy metabolism. It is vigorously debated whether peroxisomes are involved in isoprenoid and cholesterol synthesis in animals. Other known peroxisomal functions include the glyoxylate cycle in germinating seeds ("glyoxysomes"), photorespiration in leaves, glycolysis in trypanosomes ("glycosomes"), and methanol and/or amine oxidation and assimilation in some yeasts.
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.
Eicosanoids are signaling molecules made by the enzymatic or non-enzymatic oxidation of arachidonic acid or other polyunsaturated fatty acids (PUFAs) that are, similar to arachidonic acid, around 20 carbon units in length. Eicosanoids are a sub-category of oxylipins, i.e. oxidized fatty acids of diverse carbon units in length, and are distinguished from other oxylipins by their overwhelming importance as cell signaling molecules. Eicosanoids function in diverse physiological systems and pathological processes such as: mounting or inhibiting inflammation, allergy, fever and other immune responses; regulating the abortion of pregnancy and normal childbirth; contributing to the perception of pain; regulating cell growth; controlling blood pressure; and modulating the regional flow of blood to tissues. In performing these roles, eicosanoids most often act as autocrine signaling agents to impact their cells of origin or as paracrine signaling agents to impact cells in the proximity of their cells of origin. Eicosanoids may also act as endocrine agents to control the function of distant cells.
Lipid peroxidation is the chain of reactions of oxidative degradation of lipids. It is the process in which free radicals "steal" electrons from the lipids in cell membranes, resulting in cell damage. This process proceeds by a free radical chain reaction mechanism. It most often affects polyunsaturated fatty acids, because they contain multiple double bonds in between which lie methylene bridges (-CH2-) that possess especially reactive hydrogen atoms. As with any radical reaction, the reaction consists of three major steps: initiation, propagation, and termination. The chemical products of this oxidation are known as lipid peroxides or lipid oxidation products (LOPs).
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.
Docosahexaenoic acid (DHA) is an omega-3 fatty acid that is a primary structural component of the human brain, cerebral cortex, skin, and retina. In physiological literature, it is given the name 22:6(n-3). It can be synthesized from alpha-linolenic acid or obtained directly from maternal milk, fatty fish, fish oil, or algae oil.
In biochemistry and nutrition, a polyunsaturated fat is a fat that contains a polyunsaturated fatty acid, which is a subclass of fatty acid characterized by a backbone with two or more carbon–carbon double bonds. Some polyunsaturated fatty acids are essentials. Polyunsaturated fatty acids are precursors to and are derived from polyunsaturated fats, which include drying oils.
In biology, membrane fluidity refers to the viscosity of the lipid bilayer of a cell membrane or a synthetic lipid membrane. Lipid packing can influence the fluidity of the membrane. Viscosity of the membrane can affect the rotation and diffusion of proteins and other bio-molecules within the membrane, there-by affecting the functions of these things.
Heavy isotope diet is the consumption of nutrients in which some atoms are replaced with their heavier non-radioactive isotopes, such as deuterium 2H or heavy carbon 13C. Biomolecules that incorporate heavier isotopes give rise to more stable molecular structures, which is hypothesized to increase resistance to damage associated with ageing or diseases.
Fatty acid desaturase 2 (FADS2) is encoded by the FADS2 gene, the associated enzyme is sometimes known as FADS2 as well. Its main associated enzyme is Delta 6 desaturase (D6D) however the human enzyme was shown to also catalyze some delta-8 and delta-4 desaturation reactions despite naming conventions.
CYP4F2 is gene in humans that encodes Leukotriene-B4 omega-hydroxylase 1, a protein enzyme involved in metabolizing endogenous substances such as fatty acids and exogenous substance such as pharmaceutical drugs. Its primary substrate, leukotriene B4 (LTB4), plays a role as an inflammatory mediator. By hydroxylating LTB4 to form 20-hydroxy-LTB4, this enzyme helps regulate inflammation levels in the body, which is essential for maintaining balanced immune responses.
Cytostasis is the inhibition of cell growth and multiplication. Cytostatic refers to a cellular component or medicine that inhibits cell division.
Oxytosis/ferroptosis is a type of programmed cell death dependent on iron and characterized by the accumulation of lipid peroxides, and is genetically and biochemically distinct from other forms of regulated cell death such as apoptosis. Oxytosis/ferroptosis is initiated by the failure of the glutathione-dependent antioxidant defenses, resulting in unchecked lipid peroxidation and eventual cell death. Lipophilic antioxidants and iron chelators can prevent ferroptotic cell death. Although the connection between iron and lipid peroxidation has been appreciated for years, it was not until 2012 that Brent Stockwell and Scott J. Dixon coined the term ferroptosis and described several of its key features. Pamela Maher and David Schubert discovered the process in 2001 and called it oxytosis. While they did not describe the involvement of iron at the time, oxytosis and ferroptosis are today thought to be the same cell death mechanism.
A deuterated drug is a small molecule medicinal product in which one or more of the hydrogen atoms contained in the drug molecule have been replaced by its heavier stable isotope deuterium. Because of the kinetic isotope effect, deuterium-containing drugs may have significantly lower rates of metabolism, and hence a longer half-life.
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.
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.
Chain reaction in chemistry and physics is a process that produces products capable of initiating subsequent processes of a similar nature. It is a self-sustaining sequence in which the resulting products continue to propagate further reactions. There are at least two examples of chain reactions in living organisms.
