Glutamine
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| Structure of L -glutamine, the naturally occurring enantiomer | |||||||||||||||||||
| General | |||||||||||||||||||
| Surname | Glutamine | ||||||||||||||||||
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| Molecular formula | C 5 H 10 N 2 O 3 | ||||||||||||||||||
| Brief description |
colorless and odorless solid |
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| properties | |||||||||||||||||||
| Molar mass | 146.15 g mol −1 | ||||||||||||||||||
| Physical state |
firmly |
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| Melting point |
185-186 ° C |
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| As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions . | |||||||||||||||||||
Glutamine is a proteinogenic , not essential for the human α - amino acid and represents the γ-mono amide of L - glutamic acid . Constitute the three-letter code being as Gln and the single letter code as Q , respectively. In the metabolism is L -glutamine a universal amino - donor . In the blood plasma glutamine comes with a proportion of 20% as a main component of the pool of free amino acids before. In hyper catabolic and hyper metabolic disease states such. B. After operations, severe injuries, burns and infections, a pronounced glutamine depletion can always be observed. Glutamine is a base triplet CAG or CAA of the mRNA encoding .
Enantiomers
Glutamine has a stereocenter, so there are two chiral enantiomers . In the proteins, in addition to other amino acids, only L- glutamine [synonym: ( S ) -glutamine] occurs in peptide bonds . D- glutamine [synonym: ( R ) -glutamine], which does not occur in proteins, has a mirror image of this . Racemic DL -glutamine [synonyms: ( RS ) -glutamine and (±) -glutamine] is of little importance.
Whenever “glutamine” is mentioned in this text or in the scientific literature without any additional name ( descriptor ), L- glutamine is meant.
| Enantiomers of Glutamine | ||
| Surname | L -glutamine | D -glutamine |
| other names | ( S ) -glutamine | ( R ) -glutamine |
| Structural formula | |
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| CAS number | 56-85-9 | 5959-95-5 |
| 6899-04-3 (unspec.) | ||
| EC number | 200-292-1 | 673-968-0 |
| 230-006-0 (unspec.) | ||
| ECHA info card | 100,000,266 | 100.199.389 |
| 100.027.278 (unspec.) | ||
| PubChem | 5961 | 145815 |
| 738 (unspec.) | ||
| DrugBank | DB00130 | DB02174 |
| - (racemate) | ||
| Wikidata | Q181619 | Q27102193 |
| Q27103623 (unspec.) | ||
Occurrence
Glutamine occurs in an average of 3.9% - bound in proteins ; The amino acid is also often found in free form in all plants, animals, fungi and bacteria as the central metabolite in the metabolism of all living things.
Are foods high in glutamine
| Food | Glutamine [mg / 100g] |
|---|---|
| wheat | 4080 |
| Spelled flour | 5170 |
| lenses | 4490 |
| Mung bean | 4810 |
| Soybeans | 6490 |
| peanuts | 5630 |
| cheese | 3050-8100 |
| beef | 4130 |
| Mutton | 4300 |
| pork meat | 3910 |
All of these foods contain almost exclusively chemically bound L -glutamine as a protein component, but no free L -glutamine.
history
L -glutamine was first described in 1877. Together with one of his doctoral students, Ernst Schulze came to the conclusion that glutamic acid is present in beetroot as an amide, which they called glutamine (analogous to asparagine and aspartic acid ). Shortly afterwards, Ernst Schulze examined these relationships in pumpkin seedlings and came to the same conclusion. The structure elucidation for glutamic acid / glutamine had already been carried out in 1872 by the German chemist Wilhelm Dittmar . At that time, Dittmar was working at the agricultural chemical research institute in Bonn-Poppelsdorf under Heinrich Ritthausen , who had already discovered glutamic acid in 1866.
properties
The colorless, crystalline glutamine is insoluble in alcohols , benzene and chloroform . On the other hand, it is moderately soluble in water (100 g / l at 40 ° C).
- Van der Waals volume : 114
- Lipid solubility : LogP = −3.5
Glutamine is mainly present as an “inner salt” or zwitterion , the formation of which can be explained by the fact that the proton of the carboxy group migrates to the lone pair of electrons on the nitrogen atom of the amino group .
The zwitterion does not migrate in the electric field because it is uncharged as a whole. Strictly speaking, this is the case at the isoelectric point (at a certain pH value), at which the zwitterion also has its lowest solubility in water. Its isoelectric point is 5.65.
Manufacturing
L- glutamine is produced on an industrial scale by fermentation .
biochemistry
For the biosynthesis including structural formulas see section web links.
L -glutamine is made from L - glutamic acid by glutamine synthetase . Here is adenosine triphosphate (ATP) is consumed. In the body, L- glutamine can be broken down into succinate in three reaction steps.
Functions
With a proportion of 20%, glutamine is the main component of the pool of free amino acids in the blood plasma (400–600 µmol / l). Glutamine is found in the highest concentration in the muscle cells (approx. 35 mmol / l), which also mainly synthesize it. Among other things, it is responsible for water retention in the cell and causes an increase in cell volume during physical exertion, which is to be regarded as an anabolic signal that supports proliferation . This means that protein and glycogen formation is promoted.
Hypercatabolic and hypermetabolic disease states are associated with a clear depletion of glutamine in the blood and in the muscles, without the reactive increase in glutamine synthesis. A characteristic of the reaction to trauma or infection is the reduction of free glutamine in the muscles by around 50%. This loss of intracellular glutamine was found both after selective surgery, multiple trauma and burns, as well as in infections and pancreatitis regardless of diet. Glutamine is not only a building block for protein synthesis, but also a. also represents an important substrate for the cells of the gastrointestinal tract ( enterocytes , colonocytes ) and for liver cells . From this the thesis was developed that glutamine is a conditionally essential amino acid, which is particularly necessary in severe illnesses. Accordingly, the hypothesis emerged that glutamine supplementation would lead to better results in seriously ill patients .
On the other hand showed an international multicenter randomized double -blind study of over 1200 seriously ill mechanically ventilated ICU patients with multi-organ failure , both in the treatment group enterally and parenterally received glutamine, a significantly increased mortality of 32.4% (placebo 27.2%) with an adjusted risk factor of 1.09 after 28 days. Even after six months, mortality was significantly higher with glutamine treatment, but glutamine had no influence on organ failure or the infection rate. Glutamine substitution thus appears obsolete in intensive care medicine, and one comment even speaks of “glutamine toxicity”. The reduced glutamine level in seriously ill patients could therefore be less a consequence of a deficiency than a positive adaptation mechanism.
Function in the nervous system
Glutamine is chemically closely related to the excitatory amino acid glutamic acid (often only the ionized form, glutamate, is spoken of), which occurs as a neurotransmitter in glutamatergic synapses in the central nervous system. At these synapses, part of the glutamate is absorbed into neighboring glial cells after it has been released into the synaptic gap . In order to transport the ingested glutamate back into the presynaptic neurons , it is converted into glutamine in the glial cells, since glutamine has no excitatory effect on the postsynaptic membrane. Glutamine is then converted back into glutamate in the neurons.
Function in the cell culture of tumor cells
A large excess of glutamine is necessary for the cell culture of many tumor cells . As already mentioned above, the human blood has a concentration of 500 to 900 µmol / l glutamine, in cell culture, however, 2000–4000 µmol / l is usually used. This is because many types of tumor cells absorb and metabolize significantly more glutamine than normal body cells. The reasons are currently much discussed in the scientific literature. Various authors suggest the increased expression of the oncogene myc as a possible cause for the increased glutamine uptake and dependence of tumors . Because of this dependency, various glutamine analogs such as DON , azaserine or acivicin are and have been tested for the treatment of various solid tumors.
Polyglutamine
A number of important proteins contain polyglutamine units, that is, longer, repeating glutamine-glutamine linkages. Example is the FOXP2 protein or the Huntington's disease -causing huntingtin . In huntingtin one by one causes autosomal - dominant mutation conditional extension of the polyglutamine unit the outbreak of the disease.
Web links
Individual evidence
- ↑ a b c d e f Data sheet S - (+) - Glutamine (PDF) from Merck , accessed on February 15, 2013.
- ↑ a b CRC Handbook of Chemistry and Physics, Ed. DR Lide, 85th Ed., CRC Press, Boca Raton, FL, 2005.
- ↑ a b entry on L-glutamine. In: Römpp Online . Georg Thieme Verlag, accessed on October 13, 2013.
- ↑ Glutamine content of foods. DocMedicus, German Society for Nutrient Medicine and Prevention, accessed on October 13, 2013.
- ↑ S. Hansen: Discovery of Amino Acids ( Memento from June 15, 2016 in the Internet Archive ), Berlin 2015.
- ↑ PM Hardy: The Protein Amino Acids. In: GC Barrett (editor): Chemistry and Biochemistry of the Amino Acids. Chapman and Hall, 1985, ISBN 0-412-23410-6 , p. 9.
- ↑ Yoshiharu Izumi, Ichiro Chibata and Tamio Itoh: Production and Use of Amino Acids. In: Angewandte Chemie 90 (1978) 187-194; Angewandte Chemie International Edition in English 17 , 176–183.
- ^ PB Soeters, I. Grecu: Have we enough glutamine and how does it work? A clinician's view. In: Annals of nutrition & metabolism. Volume 60, number 1, 2012, pp. 17-26, doi : 10.1159 / 000334880 , PMID 22212454 (review). ( free full text ).
- ↑ Daren Heyland, John Muscedere u. a .: A Randomized Trial of Glutamine and Antioxidants in Critically Ill Patients. In: New England Journal of Medicine. 368, 2013, pp. 1489–1497, doi : 10.1056 / NEJMoa1212722 .
- ↑ Greet Van den Berghe: Low Glutamine Levels during Critical Illness - Adaptive or Maladaptive? In: New England Journal of Medicine. 368, 2013, pp. 1549–1550, doi : 10.1056 / NEJMe1302301 .
- ^ BC Fuchs, BP Bode: Amino acid transporters ASCT2 and LAT1 in cancer: partners in crime? In: Seminars in Cancer Biology . Volume 15, Number 4, August 2005, pp. 254-266, doi : 10.1016 / j.semcancer.2005.04.005 , PMID 15916903 .
- ↑ M. Yuneva, N. Zamboni et al. a .: Deficiency in glutamine but not glucose induces MYC-dependent apoptosis in human cells. In: Journal of Cell Biology . Volume 178, Number 1, July 2007, pp. 93-105, doi : 10.1083 / jcb.200703099 . PMID 17606868 . PMC 2064426 (free full text).
- ↑ DR Wise, RJ DeBerardinis u. a .: Myc regulates a transcriptional program that stimulates mitochondrial glutaminolysis and leads to glutamine addiction. In: Proceedings of the National Academy of Sciences . Volume 105, Number 48, December 2008, pp. 18782-18787, doi : 10.1073 / pnas.0810199105 . PMID 19033189 . PMC 2596212 (free full text).
- ^ J. Rutishauser: Huntington's disease: disrupt the fatal attraction. (PDF; 163 kB) In: Schweiz Med Forum , 24/2002, pp. 586-587.
- ↑ E. Cattaneo et al. a: The puzzle of Huntington's disease. In: Spectrum of Science , JANUARY 2004, pp. 60–66.