Proline

Source: Wikipedia, the free encyclopedia.
For other uses, see Proline (disambiguation).
Not to be confused with Prolene.
Proline
Structural formula of proline
Structural formula of proline
Names
IUPAC name
Proline
Systematic IUPAC name
Pyrrolidine-2-carboxylic acid[1]
Identifiers
3D model (
JSmol
)
80812
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard
 100.009.264 Edit this at Wikidata
EC Number
  • L: 210-189-3
26927
KEGG
MeSH Proline
RTECS number
  • L: TW3584000
UNII
  • InChI=1S/C5H9NO2/c7-5(8)4-2-1-3-6-4/h4,6H,1-3H2,(H,7,8)/t4-/m0/s1 checkY
    Key: ONIBWKKTOPOVIA-BYPYZUCNSA-N checkY
  • D/L: Key: ONIBWKKTOPOVIA-UHFFFAOYSA-N
  • D: Key: ONIBWKKTOPOVIA-SCSAIBSYSA-N
  • L: C1C[C@H](NC1)C(=O)O
  • L Zwitterion: [O-]C(=O)[C@H](CCC2)[NH2+]2
Properties
C5H9NO2
Molar mass 115.132 g·mol−1
Appearance Transparent crystals
Melting point 205 to 228 °C (401 to 442 °F; 478 to 501 K) (decomposes)
Solubility 1.5g/100g ethanol 19 degC[2]
log P -0.06
Acidity (pKa) 1.99 (carboxyl), 10.96 (amino)[3]
Supplementary data page
Proline (data page)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Proline (symbol Pro or P)

codons
starting with CC (CCU, CCC, CCA, and CCG).

Proline is the only proteinogenic secondary amino acid which is a secondary amine, as the nitrogen atom is attached both to the α-carbon and to a chain of three carbons that together form a five-membered ring.

History and etymology

Proline was first isolated in 1900 by

1,3-dibromopropane. The next year, Emil Fischer isolated proline from casein and the decomposition products of γ-phthalimido-propylmalonic ester,[5] and published the synthesis of proline from phthalimide propylmalonic ester.[6]

The name proline comes from pyrrolidine, one of its constituents.[7]

Biosynthesis

Proline is

1-pyrroline-5-carboxylic acid, which is reduced to proline by pyrroline-5-carboxylate reductase (using NADH or NADPH), or turned into ornithine by ornithine aminotransferase, followed by cyclisation by ornithine cyclodeaminase to form proline.[8]

Zwitterionic structure of both proline enantiomers: (S)-proline (left) and (R)-proline

Biological activity

L-Proline has been found to act as a weak

plants, proline accumulation is a common physiological response to various stresses but is also part of the developmental program in generative tissues (e.g. pollen).[12][13][14][15]

A diet rich in proline was linked to an increased risk of depression in humans in a study from 2022 that was tested on a limited pre-clinical trial on humans and primarily in other organisms. Results were significant in the other organisms.[16]

Properties in protein structure

The distinctive cyclic structure of proline's side chain gives proline an exceptional conformational rigidity compared to other amino acids. It also affects the rate of peptide bond formation between proline and other amino acids. When proline is bound as an amide in a peptide bond, its nitrogen is not bound to any hydrogen, meaning it cannot act as a hydrogen bond donor, but can be a hydrogen bond acceptor.

Peptide bond formation with incoming Pro-tRNAPro in the ribosome is considerably slower than with any other tRNAs, which is a general feature of N-alkylamino acids.[17] Peptide bond formation is also slow between an incoming tRNA and a chain ending in proline; with the creation of proline-proline bonds slowest of all.[18]

The exceptional conformational rigidity of proline affects the

secondary structure of proteins near a proline residue and may account for proline's higher prevalence in the proteins of thermophilic organisms. Protein secondary structure can be described in terms of the dihedral angles φ, ψ and ω of the protein backbone. The cyclic structure of proline's side chain locks the angle φ at approximately −65°.[19]

Proline acts as a structural disruptor in the middle of regular

aliphatic
side chain.

Multiple prolines and/or

prolyl hydroxylase (or other additions of electron-withdrawing substituents such as fluorine) increases the conformational stability of collagen significantly.[20] Hence, the hydroxylation of proline is a critical biochemical process for maintaining the connective tissue of higher organisms. Severe diseases such as scurvy can result from defects in this hydroxylation, e.g., mutations in the enzyme prolyl hydroxylase or lack of the necessary ascorbate (vitamin C)
cofactor.

Cis–trans isomerization

trans isomers. Most peptide bonds overwhelmingly adopt the trans isomer (typically 99.9% under unstrained conditions), chiefly because the amide hydrogen (trans isomer) offers less steric repulsion to the preceding Cα atom than does the following Cα atom (cis isomer). By contrast, the cis and trans isomers of the X-Pro peptide bond (where X represents any amino acid) both experience steric clashes with the neighboring substitution and have a much lower energy difference. Hence, the fraction of X-Pro peptide bonds in the cis isomer under unstrained conditions is significantly elevated, with cis fractions typically in the range of 3-10%.[21] However, these values depend on the preceding amino acid, with Gly[22] and aromatic[23] residues yielding increased fractions of the cis isomer. Cis fractions up to 40% have been identified for aromatic–proline peptide bonds.[24]

From a kinetic standpoint, cis–trans proline isomerization is a very slow process that can impede the progress of protein folding by trapping one or more proline residues crucial for folding in the non-native isomer, especially when the native protein requires the cis isomer. This is because proline residues are exclusively synthesized in the ribosome as the trans isomer form. All organisms possess prolyl isomerase enzymes to catalyze this isomerization, and some bacteria have specialized prolyl isomerases associated with the ribosome. However, not all prolines are essential for folding, and protein folding may proceed at a normal rate despite having non-native conformers of many X–Pro peptide bonds.

Uses

Proline and its derivatives are often used as asymmetric catalysts in

CBS reduction and proline catalysed aldol condensation
are prominent examples.

In brewing, proteins rich in proline combine with polyphenols to produce haze (turbidity).[25]

L-Proline is an osmoprotectant and therefore is used in many pharmaceutical and biotechnological applications.

The

better source needed] For proline's role in the stress response of plants, see § Biological activity
.

Specialties

Proline is one of the two amino acids that do not follow along with the typical Ramachandran plot, along with glycine. Due to the ring formation connected to the beta carbon, the ψ and φ angles about the peptide bond have fewer allowable degrees of rotation. As a result, it is often found in "turns" of proteins as its free entropy (ΔS) is not as comparatively large to other amino acids and thus in a folded form vs. unfolded form, the change in entropy is smaller. Furthermore, proline is rarely found in α and β structures as it would reduce the stability of such structures, because its side chain α-nitrogen can only form one nitrogen bond.

Additionally, proline is the only amino acid that does not form a red-purple colour when developed by spraying with ninhydrin for uses in chromatography. Proline, instead, produces an orange-yellow colour.

Synthesis

Racemic proline can be synthesized from diethyl malonate and acrylonitrile:[27]

See also

References

  1. ^ "Proline". PubChem. U.S. National Library of Medicine. Archived from the original on 16 January 2014. Retrieved 8 May 2018.
  2. ISBN 978-3-540-69933-0. Archived
    from the original on 2016-05-15.
  3. ^ Nelson DL, Cox MM. Principles of Biochemistry. New York: W.H. Freeman and Company.
  4. ^ "Nomenclature and Symbolism for Amino Acids and Peptides". IUPAC-IUB Joint Commission on Biochemical Nomenclature. 1983. Archived from the original on 9 October 2008. Retrieved 5 March 2018.
  5. ^ Plimmer RH (1912) [1908], Plimmer RH, Hopkins FG (eds.), The chemical composition of the proteins, Monographs on biochemistry, vol. Part I. Analysis (2nd ed.), London: Longmans, Green and Co., p. 130, retrieved September 20, 2010
  6. ^ "Proline". Amino Acids Guide. Archived from the original on 2015-11-27.
  7. ^ "Proline". American Heritage Dictionary of the English Language, 4th edition. Archived from the original on 2015-09-15. Retrieved 2015-12-06.
  8. ISBN 1-57259-153-6
    ..
  9. ^
    ISBN 978-0-08-053519-7. Archived
    from the original on 26 April 2016.
  10. ^
    PMID 1349155
    .
  11. ^
    ISBN 978-1-4398-4833-3. Archived
    from the original on 14 May 2016.
  12. S2CID 21788988
    .
  13. S2CID 252438394
    .
  14. S2CID 233397785
    .
  15. PMID 30131422
    .
  16. S2CID 248528026
    .
  17. PMID 19104062
    ..
  18. PMID 23288527
    .
  19. S2CID 940786
    .
  20. doi:10.1016/j.jas.2011.07.022. Archived
    from the original on 2012-01-18.
  21. PMID 29064600
    .
  22. PMID 6589627
    .
  23. PMID 16478167
    .
  24. PMID 28506462
    .
  25. ^ Siebert KJ. "Haze and Foam". Cornell AgriTech. Archived from the original on 2010-07-11. Retrieved 2010-07-13. Accessed July 12, 2010.
  26. S2CID 84495391
    .
  27. ^ Vogel, Practical Organic Chemistry 5th edition

Further reading

  • Balbach J, Schmid FX (2000). "Proline isomerization and its catalysis in protein folding". In Pain RH (ed.). Mechanisms of Protein Folding (2nd ed.). Oxford University Press. pp. 212–249.
    ISBN 978-0-19-963788-1
    .    .

External links
Retrieved from "https://en.wikipedia.org/w/index.php?title=Proline&oldid=1194533922"