Squalene

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Structural formula
Structural formula of squalene
General
Surname Squalene
other names
  • 2,6,10,15,19,23-hexamethyl-2,6,10,14,18,22-tetracosahexaene
  • Spinacene
  • Supra
Molecular formula C 30 H 50
Brief description

colorless, oily liquid with a faint odor

External identifiers / databases
CAS number 111-02-4
EC number 203-826-1
ECHA InfoCard 100.003.479
PubChem 638072
ChemSpider 553635
DrugBank DB11460
Wikidata Q407560
properties
Molar mass 410.71 g mol −1
Physical state

liquid

density

0.86 g cm −3

Melting point

-75.0 ° C

boiling point

275 ° C (20 hPa)

solubility

almost insoluble in water

Refractive index

1.4990 (20 ° C)

safety instructions
GHS labeling of hazardous substances
08 - Dangerous to health

danger

H and P phrases H: 304
P: 301 + 310-331
Toxicological data
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions . Refractive index: Na-D line , 20 ° C

Squalene (with an emphasis on the last syllable squal e n ), empirical formula : C 30 H 50 , is an organic, unsaturated compound from the group of triterpenes and the group of hydrocarbons that is produced by all higher organisms. The substance also plays an important role in the human metabolism.

history

Squalene was discovered in shark liver by Mitsumaru Tsujimoto in 1906 and isolated as a pure substance in 1916. He recognized it as a hydrocarbon, determined the correct molecular formula C 30 H 50 and suggested the name "squalene" because of its origin from shark liver, after the family of the Squalidae ( squalus , Latin for shark ). Systematic medical research was only initiated in 1930 by Keijiro Kogami from Tokyo Imperial University.

Nobel laureate Paul Karrer verified the exact chemical structure of squalene through total synthesis in 1931. In 1935, squalene was first found in olive oil and thus in a vegetable product.

Natural occurrence

Squalene is widespread in nature because it occurs in all higher living beings and therefore also in humans. It is an essential component of skin lipids and is also found in human blood serum . The natural amount of endogenous squalene in human blood is around 250 ng / ml.

Squalene occurs in high concentrations in various foods, for example in goat milk and in many vegetable oils such as olive oil (0.1–0.7%), wheat germ oil or rice oil (below 0.03%). The main occurrence, however, are fish oils. The content is highest in cod liver oil from various sharks (40–90%), but it is also found in high proportions (up to 30%) in many other fish oils .

Properties and biological effect

Squalene is a colorless, oily liquid that, due to its unsaturated character, absorbs oxygen from the air and polymerizes easily . It is almost insoluble in water, but readily soluble in acetone , ether , petroleum ether and other non-polar solvents . Squalene is an antioxidant and, unlike most other antioxidants, it can be stored in higher concentrations in the body. For example, lycopene and ubiquinone cannot be stored in the human body at a high level because they are toxic at concentrations of more than 10 µM , while squalene is non-toxic even at 100 µM.

Squalene found in food is largely absorbed through the gastrointestinal tract and metabolized in the body.

use

Squalene is industrially hydrogenated to squalane , which is used as an ointment base , but also as a lubricant and transformer oil .

Squalene is a component of adjuvants such as AS03 and MF59 , which are added to vaccines as potentiators . Pure squalene itself does not act as an adjuvant. Squalene-containing adjuvants as emulsions are contained, for example, in the vaccines Pandemrix or Celtura , which were used in Germany to contain the H1N1 2009 pandemic as part of the swine flu vaccination . The amount of squalene contained in vaccines does not exceed the amount that is consumed daily through food. For use in vaccines, the squalene used must have a high purity content. This is usually obtained from the liver of sharks, especially dogfish . Alternative sources from plants (“phytosqualane”) or from microorganisms (e.g. from marine yeasts ) are being investigated. In addition, squalene is being tested as a component of newer adjuvants such as CAF19 and CAF24 ( Cationic Adjuvant Formulation ).

In alternative medicine , shark liver oil is used as a remedy for cancer and atopic eczema . There is currently insufficient evidence in the form of clinical studies for the use of shark liver oil or one of its components as a therapeutic agent - but experimental work on animals indicates a possible effectiveness.

biosynthesis

Squalene is synthesized from isopentenyl pyrophosphate through a series of condensation reactions. Geranyl pyrophosphate is initially formed , which then condenses with isopentenyl pyrophosphate to form farnesyl pyrophosphate . All condensations catalyzed the Geranyltransferase . Two molecules of farnesyl pyrophosphate are finally linked to form squalene by consuming NADPH , which is catalyzed by squalene synthase in the endoplasmic reticulum .

The tail-to-tail linkage of two molecules of farnesyl pyrophosphate to form squalene catalyzes squalene synthase

Analytics

The reliable qualitative and quantitative determination in the various test items is possible after appropriate sample preparation by coupling gas chromatography with mass spectrometry . The method can also be used for forensic examinations of fingerprints .

function

Squalene is used for the synthesis of all cyclic triterpenes and steroids formed as an intermediate, for example in the biosynthesis of cholesterol , steroids (hormones such as u. A. Estrogens , testosterone , cortisol ) and Vitamin D . Squalene is first activated by a monooxygenase with consumption of NADPH, resulting in squalene epoxide (2,3-oxidosqualene). This is finally cyclized into lanosterol by the oxidosqualene cyclase . A series of subsequent reactions produce either cholesterol or ergosterol .

Cholesterolsynthesis.png
Biosynthetic scheme for cholesterol with squalene folding
Ergosterol-Biosynthesis.png
Biosynthetic scheme for ergosterol with squalene folding

Health controversy

Due to its activating effect on the immune system, it has often been assumed that squalene can trigger autoimmune diseases or promote their development under certain conditions. Among other things, squalene was associated with the Gulf War Syndrome , as it was supposedly contained in the anthrax vaccine with which American soldiers involved in the 1991 Gulf War were to be immunized against the anthrax bacterium Bacillus anthracis, which can be used as a biological weapon.

The association between squalene and Gulf War Syndrome is based primarily on a study from 2000 by Asa et al. repatriated with 144 Gulf War veterans. The results of this study indicate that antibodies to squalene were found in 95% of the examined veterans with Gulf War Syndrome and in 0% (<0.001%) of the non-infected veterans, which was taken as an indication of a connection between squalene and symptoms. However, the study concluded with the statement: "It is important to note that we could not find any evidence in our investigations that squalene was used as an adjuvant in the vaccines for military or other personnel." Subsequent investigations also identified serious methodological deficiencies in the study notes.

In a study published in 2002, Asa et al. again a connection between squalene antibodies and the symptoms of the Gulf War syndrome, which is due to the presence of squalene in some of the vaccine doses. However, other studies showed that the vaccines used did not contain squalene as an enhancer. With an improved analytical method, slight traces (80 ng / ml) of squalene were found later in a single bottle (designation FAV008) out of 44 bottles from a total of 38 batches. However, this was not added as an adjuvant, but is presumably the result of contamination from fingerprints on inadequately cleaned laboratory equipment.

Later studies disproved a link between squalene and Gulf War Syndrome, finding that many people have squalene antibodies in their blood regardless of vaccination.

In addition to Gulf War Syndrome, tissue injection of squalene has been linked to various other autoimmune diseases. In animal experiments, the development of arthritis was observed in a strain of rats which was particularly susceptible to autoimmune diseases after intradermal injection of pure squalene . In a study on healthy mice, after intraperitoneal injection of squalene and pristane , a similar substance, the formation of autoantibodies typical of the autoimmune disease lupus erythematosus was demonstrated.

An epidemiological analysis of the data on the safety of MF59 (squalene-containing) adjuvanted seasonal and pandemic influenza vaccines did not reveal any evidence of an increased risk of side effects of autoimmune origin in humans.

Since 1997 (in Germany since 2000), squalene has been administered in over 40 million doses as a component of the Fluad vaccine against seasonal flu, without any notable side effects. Furthermore, there is no evidence that squalene in vaccines has an embryotoxic or foetotoxic effect.

Individual evidence

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  2. ↑ Maria Z. Tsimidou et al .: Squalene Resources and Uses Point to the Potential of Biotechnology. In: Lipid Technology . Vol. 23, No. 12, 2011, pp. 270-273, doi: 10.1002 / lite.201100157 .
  3. ↑ a b c Entry on 2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene in the GESTIS substance database of the IFA , accessed on January 10, 2017(JavaScript required) .
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