関: proline

WordNet

the 12th letter of the Roman alphabet (同)l
an amino acid that is found in many proteins (especially collagen)

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/07/23 10:02:22」(JST)

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Proline (abbreviated as Pro or P) is an α-amino acid, one of the twenty DNA-encoded amino acids. Its codons are CCU, CCC, CCA, and CCG. It is not an essential amino acid, which means that the human body can synthesize it. It is unique among the 20 protein-forming amino acids in that the amine nitrogen is bound to not one but two alkyl groups, thus making it a secondary amine. The more common L form has S configuration.

Biosynthesis

Proline is biosynthetically derived from the amino acid L-glutamate. Glutamate-5-semialdehyde is first formed by glutamate 5-kinase (ATP-dependent) and glutamate-5-semialdehyde dehydrogenase (which requires NADH or NADPH). This can then either spontaneously cyclize to form 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.^[4]

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

Biological activity

L-Proline has been found to act as a weak agonist of the glycine receptor and of both NMDA and non-NMDA (AMPA/kainate) ionotropic glutamate receptors.^[5]^[6]^[7] It has been proposed to be a potential endogenous excitotoxin.^[5]^[6]^[7] In 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). ^[8]

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-tRNA^Pro is considerably slower than with any other tRNAs, which is a general feature of N-alkylamino acids.^[9] 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.^[10]

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 −60°.

Proline acts as a structural disruptor in the middle of regular secondary structure elements such as alpha helices and beta sheets; however, proline is commonly found as the first residue of an alpha helix and also in the edge strands of beta sheets. Proline is also commonly found in turns (another kind of secondary structure), and aids in the formation of beta turns. This may account for the curious fact that proline is usually solvent-exposed, despite having a completely aliphatic side chain.

Multiple prolines and/or hydroxyprolines in a row can create a polyproline helix, the predominant secondary structure in collagen. The hydroxylation of proline by prolyl hydroxylase (or other additions of electron-withdrawing substituents such as fluorine) increases the conformational stability of collagen significantly.^[11] 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

Peptide bonds to proline, and to other N-substituted amino acids (such as sarcosine), are able to populate both the cis and 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 C_α atom than does the following C_α 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 are nearly equal energetically. Hence, the fraction of X-Pro peptide bonds in the cis isomer under unstrained conditions ranges from 10-40%; the fraction depends slightly on the preceding amino acid, with aromatic residues favoring the cis isomer slightly.

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 proline organocatalysis reactions. The CBS reduction and proline catalysed aldol condensation are prominent examples.

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

In brewing, proteins rich in proline combine with polyphenols to produce haze (turbidity).^[12]

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 less. Furthermore, proline is rarely found in α and β structures as it would reduce the stability of such structures, because its side chain α-N can only form one hydrogen bond.

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

History

Richard Willstätter synthesized proline by the reaction of sodium salt of diethyl malonate with 1,3-dibromopropane in 1900. In 1901, Hermann Emil Fischer isolated proline from casein and the decomposition products of γ-phthalimido-propylmalonic ester.^[13]

Synthesis

Racemic proline can be synthesized from diethyl malonate and acrylonitrile:^[14]

References

^ http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=614&loc=ec_rcs
^ H.-D. Belitz; W. Grosch; P. Schieberle. Food Chemistry. p. 15. ISBN 978-3-540-69933-0.
^ Nelson, D.L., Cox, M.M., Principles of Biochemistry. NY: W.H. Freeman and Company.
^ Lehninger, Albert L.; Nelson, David L.; Cox, Michael M. (2000), Principles of Biochemistry (3rd ed.), New York: W. H. Freeman, ISBN 1-57259-153-6 .
^ ^a ^b Ion Channel Factsbook: Extracellular Ligand-Gated Channels. Academic Press. 16 November 1995. pp. 126–. ISBN 978-0-08-053519-7.
^ ^a ^b Henzi V, Reichling DB, Helm SW, MacDermott AB (1992). "L-proline activates glutamate and glycine receptors in cultured rat dorsal horn neurons". Mol. Pharmacol. 41 (4): 793–801. PMID 1349155.
^ ^a ^b Orhan E. Arslan (7 August 2014). Neuroanatomical Basis of Clinical Neurology, Second Edition. CRC Press. pp. 309–. ISBN 978-1-4398-4833-3.
^ Verbruggen N, Hermans C (2008). "Proline accumulation in plants: a review.". Amino Acids 35 (4): 753–759. doi:10.1007/s00726-008-0061-6. PMID 18379856.
^ Pavlov, Michael Y; Watts, Richard E; Tan, Zhongping; Cornish, Virginia W; Ehrenberg, Måns; Forster, Anthony C (2010), "Slow peptide bond formation by proline and other N-alkylamino acids in translation", PNAS 106 (1): 50–54, doi:10.1073/pnas.0809211106, PMC 2629218, PMID 19104062 .
^ Buskirk, Allen R.; Green, Rachel (2013). "Getting Past Polyproline Pauses". Science 339 (6115): 38–39. doi:10.1126/science.1233338.
^ Szpak, Paul (2011). "Fish bone chemistry and ultrastructure: implications for taphonomy and stable isotope analysis". Journal of Archaeological Science 38 (12): 3358–3372. doi:10.1016/j.jas.2011.07.022.
^ K.J. Siebert, "Haze and Foam",[1] Accessed July 12, 2010.
^ R.H.A. Plimmer (1912) [1908], R.H.A. Plimmer & F.G. Hopkins, ed., The chemical composition of the proteins, Monographs on biochemistry, Part I. Analysis (2nd ed.), London: Longmans, Green and Co., p. 130, retrieved September 20, 2010
^ Vogel, Practical Organic Chemistry 5th edition

External links

Proline MS Spectrum
Proline biosynthesis
Proline biosynthesis

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English Journal

Interaction study between wheat-derived peptides and procyanidin B3 by mass spectrometry.

Dias R1, Perez-Gregorio MR2, Mateus N1, De Freitas V1.
Food chemistry.Food Chem.2016 Mar 1;194:1304-12. doi: 10.1016/j.foodchem.2015.08.108. Epub 2015 Aug 28.
Tannins have the ability to complex and precipitate proteins, being particularly reactive towards the proline-rich ones. The main structural feature of the wheat peptides responsible for the onset of Celiac Disease (CD) is their high content in proline residues. The aim of this work was to character
PMID 26471686

Model Membrane and Cell Studies of Antimicrobial Activity of Melittin Analogues.

Jamasbi E, Mularski A, Separovic F1.
Current topics in medicinal chemistry.Curr Top Med Chem.2016;16(1):40-5.
Melittin is a 26 residue peptide and the major component of bee (Apis mellifera) venom. Although melittin has both anticancer and antimicrobial properties, utilization has been limited due to its high lytic activity against eukaryotic cells. The mechanism of this lytic activity remains unclear but s
PMID 26139117

Effects of various amino acids as organic nitrogen sources on the growth and biochemical composition of Chlorella pyrenoidosa.

Zhang W1, Zhang Z1, Yan S2.
Bioresource technology.Bioresour Technol.2015 Dec;197:458-64. doi: 10.1016/j.biortech.2015.08.100. Epub 2015 Sep 1.
This study investigated the effects of eighteen l-amino acids on the growth and biochemical composition of Chlorella pyrenoidosa. Under the nitrate deficiency condition, ten l-amino acids were found to exert stronger stimulative effects on the algal growth than the other amino acids. After 10-day cu
PMID 26356118

Japanese Journal

L-ピペコリン酸およびL-プロリンの生成に関わる多機能性酵素 (特集タンパク質・酵素の隠された機能について,探索とその技術)

生化学 87(3), 326-332, 2015-06
NAID 40020519804

Ameliorated pancreatic β cell dysfunction in type 2 diabetic patients treated with a sodium-glucose cotransporter 2 inhibitor ipragliflozin

Endocrine Journal 62(1), 77-86, 2015
NAID 130004770464

Industrial Info. 2型糖尿病治療薬選択的SGLT2阻害薬"スーグラ"

細胞 46(12), 590-593, 2014-11
NAID 40020303394

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リンク元	「L-プロリン」
関連記事	「L」「proline」

「L-プロリン」

Proline
Names
	IUPAC name Proline
	Systematic IUPAC name Pyrrolidine-2-carboxylic acid
Identifiers
CAS Registry Number	609-36-9 ; 344-25-2 (R) ; 147-85-3 (S)
Beilstein Reference	80812
ChEBI	CHEBI:26271
ChEMBL	ChEMBL72275
ChemSpider	594 ; 8640 (R) ; 128566 (S)
DrugBank	DB00172
EC number	210-189-3
Gmelin Reference	26927
	InChI InChI=1S/C5H9NO2/c7-5(8)4-2-1-3-6-4/h4,6H,1-3H2,(H,7,8) ; Key: ONIBWKKTOPOVIA-UHFFFAOYSA-N ; InChI=1/C5H9NO2/c7-5(8)4-2-1-3-6-4/h4,6H,1-3H2,(H,7,8) ;
Jmol-3D images	Image; Image
KEGG	C16435
MeSH	Proline
PubChem	614; 8988 (R); 145742 (S)
RTECS number	TW3584000
	SMILES OC(=O)C1CCCN1 ; C1CC(NC1)C(=O)O ;
UNII	DCS9E77JPQ
Properties
Chemical formula	C5H9NO2
Molar mass	115.13 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
log P	-0.06
Acidity (pKa)	1.99 (carboxyl), 10.96 (amino)
Hazards
Safety data sheet	See: data page
S-phrases	S22, S24/25
Supplementary data page
Structure and; properties	Refractive index (n),; Dielectric constant (εr), etc.
Thermodynamic; data	Phase behaviour; solid–liquid–gas
Spectral data	UV, IR, NMR, MS
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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	Infobox references

　　[★]

英: L-proline
関: プロリン

「L」

　　[★]

「proline」

　　[★] プロリン, L-proline, Pro, P

[1] ttp://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=614&loc=ec_rcs

[2] H.-D. Belitz; W. Grosch; P. Schieberle. Food Chemistry. p. 15. ISBN 978-3-540-69933-0.

[3] Nelson, D.L., Cox, M.M., Principles of Biochemistry. NY: W.H. Freeman and Company.

[4] Lehninger, Albert L.; Nelson, David L.; Cox, Michael M. (2000), Principles of Biochemistry (3rd ed.), New York: W. H. Freeman, ISBN 1-57259-153-6 .

[AcademicPress1995-5] Ion Channel Factsbook: Extracellular Ligand-Gated Channels. Academic Press. 16 November 1995. pp. 126–. ISBN 978-0-08-053519-7.

[pmid1349155-6] Henzi V, Reichling DB, Helm SW, MacDermott AB (1992). "L-proline activates glutamate and glycine receptors in cultured rat dorsal horn neurons". Mol. Pharmacol. 41 (4): 793–801. PMID 1349155.

[Arslan2014-7] Orhan E. Arslan (7 August 2014). Neuroanatomical Basis of Clinical Neurology, Second Edition. CRC Press. pp. 309–. ISBN 978-1-4398-4833-3.

[pmid18379856-8] Verbruggen N, Hermans C (2008). "Proline accumulation in plants: a review.". Amino Acids 35 (4): 753–759. doi:10.1007/s00726-008-0061-6. PMID 18379856.

[9] Pavlov, Michael Y; Watts, Richard E; Tan, Zhongping; Cornish, Virginia W; Ehrenberg, Måns; Forster, Anthony C (2010), "Slow peptide bond formation by proline and other N-alkylamino acids in translation", PNAS 106 (1): 50–54, doi:10.1073/pnas.0809211106, PMC 2629218, PMID 19104062 .

[10] Buskirk, Allen R.; Green, Rachel (2013). "Getting Past Polyproline Pauses". Science 339 (6115): 38–39. doi:10.1126/science.1233338.

[SzpakJAS-11] Szpak, Paul (2011). "Fish bone chemistry and ultrastructure: implications for taphonomy and stable isotope analysis". Journal of Archaeological Science 38 (12): 3358–3372. doi:10.1016/j.jas.2011.07.022.

[12] K.J. Siebert, "Haze and Foam",[1] Accessed July 12, 2010.

[13] R.H.A. Plimmer (1912) [1908], R.H.A. Plimmer & F.G. Hopkins, ed., The chemical composition of the proteins, Monographs on biochemistry, Part I. Analysis (2nd ed.), London: Longmans, Green and Co., p. 130, retrieved September 20, 2010

[14] Vogel, Practical Organic Chemistry 5th edition

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L-proline