Names | |
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Preferred IUPAC name (6E,10E,14E,18E)-2,6,10,15,19,23-Hexamethyltetracosa-2,6,10,14,18,22-hexaene [1] | |
Identifiers | |
3D model (JSmol) | |
3DMet | |
1728919 | |
ChEBI | |
ChEMBL | |
ChemSpider | |
ECHA InfoCard | 100.003.479 |
EC Number |
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KEGG | |
MeSH | Squalene |
PubChem CID | |
RTECS number |
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UNII | |
CompTox Dashboard (EPA) | |
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Properties | |
C30H50 | |
Molar mass | 410.730 g·mol−1 |
Appearance | Colourless oil |
Density | 0.858 g·cm−3 |
Melting point | −5 °C (23 °F; 268 K) [2] |
Boiling point | 285 °C (545 °F; 558 K) at 3.3 kPa [3] |
log P | 12.188 |
Refractive index (nD) | 1.4956 (at 20 °C) [4] |
Viscosity | 12 cP (at 20 °C) |
Hazards | |
NFPA 704 (fire diamond) | |
Flash point | 110 °C (230 °F; 383 K) |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). |
Squalene is an organic compound. It is a triterpene with the formula C30H50. It is a colourless oil, although impure samples appear yellow. It was originally obtained from shark liver oil (hence its name, as Squalus is a genus of sharks). An estimated 12% of bodily squalene in humans is found in sebum. [5] Squalene has a role in topical skin lubrication and protection. [6]
Most plants, fungi, and animals produce squalene as biochemical precursor in sterol biosynthesis, including cholesterol and steroid hormones in the human body. [7] [8] [9] It is also an intermediate in the biosynthesis of hopanoids in many bacteria. [10]
Squalene is an important ingredient in some vaccine adjuvants: The Novartis and GlaxoSmithKline adjuvants are called MF59 and AS03, respectively. [11]
Squalene is a biochemical precursor to both steroids and hopanoids. [12] For sterols, the squalene conversion begins with oxidation (via squalene monooxygenase) of one of its terminal double bonds, resulting in 2,3-oxidosqualene. It then undergoes an enzyme-catalysed cyclisation to produce lanosterol, which can be elaborated into other steroids such as cholesterol and ergosterol in a multistep process by the removal of three methyl groups, the reduction of one double bond by NADPH and the migration of the other double bond. [13] In many plants, this is then converted into stigmasterol, while in many fungi, it is the precursor to ergosterol.[ citation needed ]
The biosynthetic pathway is found in many bacteria, [14] and most eukaryotes, though has not been found in Archaea. [15]
Squalene is biosynthesised by coupling two molecules of farnesyl pyrophosphate. The condensation requires NADPH and the enzyme squalene synthase.
Click on genes, proteins and metabolites below to link to respective articles. [§ 1]
This section is missing information about all routes currently used; market share of each.(January 2022) |
Synthetic squalene is prepared commercially from geranylacetone. [16]
In 2020, conservationists raised concerns about the potential slaughter of sharks to obtain squalene for a COVID-19 vaccine. [17]
Environmental and other concerns over shark hunting have motivated its extraction from other sources. [18] Biosynthetic processes use genetically engineered yeast or bacteria. [19] [20]
Immunologic adjuvants are substances, administered in conjunction with a vaccine, that stimulate the immune system and increase the response to the vaccine. Squalene is not itself an adjuvant, but it has been used in conjunction with surfactants in certain adjuvant formulations. [11]
An adjuvant using squalene is Seqirus' proprietary MF59, which is added to influenza vaccines to help stimulate the human body's immune response through production of CD4 memory cells. It is the first oil-in-water influenza vaccine adjuvant to be commercialised in combination with a seasonal influenza virus vaccine. It was developed in the 1990s by researchers at Ciba-Geigy and Chiron; both companies were subsequently acquired by Novartis. [11] The Influenza vaccine business of Novartis was later acquired by CSL Bering and created the company Seqirus. [21] It is present in the form of an emulsion and is added to make the vaccine more immunogenic. [11] However, the mechanism of action remains unknown. MF59 is capable of switching on a number of genes that partially overlap with those activated by other adjuvants. [22] How these changes are triggered is unclear; to date, no receptors responding to MF59 have been identified. One possibility is that MF59 affects the cell behaviour by changing the lipid metabolism, namely by inducing accumulation of neutral lipids within the target cells. [23] An influenza vaccine called FLUAD which used MF59 as an adjuvant was approved for use in the US in people 65 years of age and older, beginning with the 2016–2017 flu season. [24]
A 2009 meta-analysis assessed data from 64 clinical trials of influenza vaccines with the squalene-containing adjuvant MF59 and compared them to the effects of vaccines with no adjuvant. The analysis reported that the adjuvated vaccines were associated with slightly lower risks of chronic diseases, but that neither type of vaccines altered the rate of autoimmune diseases; the authors concluded that their data "supports the good safety profile associated with MF59-adjuvated influenza vaccines and suggests there may be a clinical benefit over non-MF59-containing vaccines". [25]
Toxicology studies indicate that in the concentrations used in cosmetics, squalene has low acute toxicity, and is not a significant contact allergen or irritant. [26] [27]
The World Health Organization and the US Department of Defense have both published extensive reports that emphasise that squalene is naturally occurring, even in oils of human fingerprints. [11] [28] The WHO goes further to explain that squalene has been present in over 22 million flu vaccines given to patients in Europe since 1997 without significant vaccine-related adverse events. [11]
Attempts to link squalene to Gulf War syndrome have been debunked. [29] [30] [31] [32]
Cholesterol is the principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.
A steroid is an organic compound with four fused rings arranged in a specific molecular configuration.
Sterol is an organic compound with formula C
17H
28O, whose molecule is derived from that of gonane by replacement of a hydrogen atom on C3 position by a hydroxyl group. It is therefore an alcohol of gonane. More generally, any compounds that contain the gonane structure, additional functional groups, and/or modified ring systems derived from gonane are called steroids. Therefore, sterols are a subgroup of the steroids. They occur naturally in most eukaryotes, including plants, animals, and fungi, and can also be produced by some bacteria. The most familiar type of animal sterol is cholesterol, which is vital to cell membrane structure, and functions as a precursor to fat-soluble vitamins and steroid hormones.
Rino Rappuoli is an Italian immunologist. He is the head of vaccine research and development (R&D) at GlaxoSmithKline (GSK) Vaccines. Previously, he has served as visiting scientist at Rockefeller University and Harvard Medical School and held roles at Sclavo, Vaccine Research and CSO, Chiron Corporation, and Novartis Vaccines.
Hopanoids are a diverse subclass of triterpenoids with the same hydrocarbon skeleton as the compound hopane. This group of pentacyclic molecules therefore refers to simple hopenes, hopanols and hopanes, but also to extensively functionalized derivatives such as bacteriohopanepolyols (BHPs) and hopanoids covalently attached to lipid A.
Cycloartenol is an important triterpenoid often found in plants. It belongs to the sterol class of steroids. It is the starting point for the synthesis of almost all plant steroids, making them chemically distinct from the steroids of fungi and animals, which are, instead, produced from lanosterol.
β-sitosterol (beta-sitosterol) is one of several phytosterols with chemical structures similar to that of cholesterol. It is a white, waxy powder with a characteristic odor, and is one of the components of the food additive E499. Phytosterols are hydrophobic and soluble in alcohols.
Triterpenes are a class of terpenes composed of six isoprene units with the molecular formula C30H48; they may also be thought of as consisting of three terpene units. Animals, plants and fungi all produce triterpenes, including squalene, the precursor to all steroids.
CYP27A1 is a gene encoding a cytochrome P450 oxidase, and is commonly known as sterol 27-hydroxylase. This enzyme is located in many different tissues where it is found within the mitochondria. It is most prominently involved in the biosynthesis of bile acids.
In immunology, an adjuvant is a substance that increases or modulates the immune response to a vaccine. The word "adjuvant" comes from the Latin word adiuvare, meaning to help or aid. "An immunologic adjuvant is defined as any substance that acts to accelerate, prolong, or enhance antigen-specific immune responses when used in combination with specific vaccine antigens."
Squalene synthase (SQS) or farnesyl-diphosphate:farnesyl-diphosphate farnesyl transferase is an enzyme localized to the membrane of the endoplasmic reticulum. SQS participates in the isoprenoid biosynthetic pathway, catalyzing a two-step reaction in which two identical molecules of farnesyl pyrophosphate (FPP) are converted into squalene, with the consumption of NADPH. Catalysis by SQS is the first committed step in sterol synthesis, since the squalene produced is converted exclusively into various sterols, such as cholesterol, via a complex, multi-step pathway. SQS belongs to squalene/phytoene synthase family of proteins.
In enzymology, a sterol 14-demethylase (EC 1.14.13.70) is an enzyme of the cytochrome P450 (CYP) superfamily. It is any member of the CYP51 family. It catalyzes a chemical reaction such as:
Zaragozic acids are a family of natural products produced by fungi. The first characterized zaragozic acids, A, B, and C were isolated from an unidentified sterile fungal culture, Sporormiella intermedia, and L. elatius, respectively. just outside the European city Zaragoza, Spain on the Jalón river. This family of natural products possesses a unique 4,8-dioxabicyclo[3.2.1]octane core, and vary in their 1-alkyl and their 6-acyl side chains.
The 2009 swine flu pandemic vaccines were influenza vaccines developed to protect against the pandemic H1N1/09 virus. These vaccines either contained inactivated (killed) influenza virus, or weakened live virus that could not cause influenza. The killed virus was injected, while the live virus was given as a nasal spray. Both these types of vaccine were produced by growing the virus in chicken eggs. Around three billion doses were produced, with delivery in November 2009.
AS03 is the trade name for a squalene-based immunologic adjuvant used in various vaccine products by GlaxoSmithKline (GSK). It is used, for example, in GSK's A/H1N1 pandemic flu vaccine Pandemrix. It is also in Arepanrix and the Q-pan for H5N1 influenza. A dose of AS03 adjuvant contains
MF59 is an immunologic adjuvant that uses squalene. It is Novartis' proprietary adjuvant that is added to influenza vaccines to help stimulate the human body's immune response through production of CD4 memory cells.
Squalene-hopene cyclase (SHC) (EC 5.4.99.17) or hopan-22-ol hydro-lyase is an enzyme in the terpene cyclase/mutase family. It catalyzes the interconversion of squalene into a pentacyclic triterpenes, hopene and hopanol. This enzyme catalyses the following chemical reactions.
Oxidosqualene cyclases (OSC) are enzymes involved in cyclization reactions of 2,3-oxidosqualene to form sterols or triterpenes.
Tetrahymanol is a gammacerane-type membrane lipid first found in the marine ciliate Tetrahymena pyriformis. It was later found in other ciliates, fungi, ferns, and bacteria. After being deposited in sediments that compress into sedimentary rocks over millions of years, tetrahymanol is dehydroxylated into gammacerane. Gammacerane has been interpreted as a proxy for ancient water column stratification.
Diplopterol is a triterpenoid molecule commonly produced by bacteria, ferns, and a few protozoans. This compound, classified as a member of the hopanoid family, is synthesized from triterpenoid precursor squalene. It is generally believed that hopanoids serve a similar function in bacteria as that of sterols in eukaryotes, which involves modulating membrane fluidity. Diplopterol serves as a useful biomarker for prokaryotic life, along with oxygen content at the time of sediment deposition.
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