Proline 38811 225177019 2008-07-12T08:32:28Z 219.77.25.254 /* Usage */ {{otheruses}} {{NatOrganicBox | image= [[Image:L-proline-skeletal.png|180px|Skeletal formula of proline]]<br>[[Image:L-proline-3D-sticks.png|160px|Stick model of the proline molecule]][[Image:L-proline-3D-balls.png|160px|Ball-and-stick model of the proline molecule]] | name=(''S'')-Pyrrolidine-2-&thinsp;carboxylic acid | PubChem = 614 | CAS = 147-85-3 | SMILES = OC(=O)[C@@H]1CCCN1 | C=5 | H=9 | N=1 | O=2 | mass=115.13 }} '''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|essential]] amino acid, which means that humans can synthesize it. It is unique among the 20 protein-forming amino acids because the α-amino group is [[secondary amine|secondary]]. == Biosynthesis == Proline is [[Biosynthesis|biosynthetically]] derived from the amino acid <small>L</small>-[[glutamate]] and its immediate precursor is the [[imino acid]] [[1-Pyrroline-5-carboxylic acid|(''S'')-1-pyrroline-5-carboxylate]] (P5C). Enzymes involved in a typical biosynthesis include:<ref>Nelson, D. L.; Cox, M. M. "Lehninger, Principles of Biochemistry" 3rd Ed. Worth Publishing: New York, 2000. ISNB 1-57259-153-6.</ref> # [[Glutamate kinase]] (ATP-dependent) # [[Glutamate dehydrogenase]] (requires NADH or NADPH) # [[Pyrroline-5-carboxylate reductase]] (requires NADH or NADPH) ==Structural properties== The distinctive cyclic structure of proline's side chain locks its <math>\phi</math> backbone [[dihedral angle]] at approximately -75°, giving proline an exceptional conformational rigidity compared to other amino acids. Hence, proline loses less conformational [[Introduction to entropy|entropy]] upon folding, which may account for its higher prevalence in the proteins of thermophilic organisms. Proline acts as a structural disruptor in the middle of regular [[secondary structure]] elements such as [[alpha helix|alpha helices]] and [[beta sheet]]s; however, proline is commonly found as the first residue of an [[alpha helix]] and also in the edge strands of [[beta sheet]]s. Proline is also commonly found in [[turn (biochemistry)|turns]], which may account for the curious fact that proline is usually solvent-exposed, despite having a completely [[aliphatic]] side chain. Because proline lacks a hydrogen on the amide group, it cannot act as a [[hydrogen bond]] donor, only as a [[hydrogen bond]] acceptor. Multiple prolines and/or [[hydroxyproline]]s 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. 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 [[hydroxylation|prolyl hydroxylase]] or lack of the necessary [[vitamin C|ascorbate (vitamin C)]] cofactor. Sequences of proline and [[2-Aminoisobutyric acid|2-aminoisobutyric acid]] (Aib) also form a helical turn structure{{Fact|date=February 2007}}. In 2006, scientists at [[Arizona_State_University|ASU]] discovered that solutions of [[Titanium_dioxide|TiO2]] illuminated with [[ultraviolet]] radiation can serve as an extremely cost-effective and accurate protein cleavage catalyst. The TiO2 catalyst preferentially and rapidly cleaves protein at sites where proline is present, while taking much longer to degrade the protein from its endpoints.<ref>{{cite journal | author = B. J. Jones, M. J. Vergne, D. M. Bunk, L. E. Locascio and M. A. Hayes | title = Cleavage of Peptides and Proteins Using Light-Generated Radicals from Titanium Dioxide | year = 2007 | journal = [[Anal. Chem.]] | volume = 79 | issue = 4 | pages = 1327–1332 | doi = 10.1021/ac0613737}}</ref> ==Cis-trans isomerization== [[Peptide bond]]s 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 <math>\mathrm{C}^{\alpha}</math> atom than does the following <math>\mathrm{C}^{\alpha}</math> 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 [[isomer]]ization is a very slow process that can impede the progress of [[protein folding]] by trapping one or more proline molecules 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]] [[enzyme]]s 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. ==Usage== Proline and its derivatives are often used as asymmetric catalysts in organic reactions. The [[CBS reduction]] and proline catalysed [[aldol condensation]] are prominent examples. L-Proline is osmoprotectant and therefore is used in many pharmaceutical, biotechnological applications. For example as an osmoprotectant in the infusions. L-proline is an ingredient in energy drinks such as "Sobe power fruit punch". <ref>http://www.sobebev.com/product_info/powerline_power.shtml beverage has 25mg of Proline.</ref> Proline has a sweet flavor with a distinct aftertaste. ==See also== * [[Collagen]] * [[Polyproline helix]] * [[Peptide bond]] (for more discussion of cis-trans isomerization) *[[Hyperprolinemia]] == External links == * [http://www.chem.qmul.ac.uk/iubmb/enzyme/reaction/AminoAcid/Pro.html Proline biosynthesis] * [http://www.compchemwiki.org/index.php?title=Proline Computational Chemistry Wiki] * [http://www.biocarta.com/pathfiles/prolinePathway.asp Proline biosynthesis] ==Notes== {{reflist}} == References == * Balbach J, Schmid FX. (2000). Proline isomerization and its catalysis in protein folding. In ''Mechanisms of Protein Folding'' 2nd ed. Editor RH Pain. Oxford University Press. * For a thorough scientific overview of disorders of proline and hydroxyproline metabolism, one can consult chapter 81 of OMMBID [[Charles Scriver]], Beaudet, A.L., Valle, D., Sly, W.S., Vogelstein, B., Childs, B., Kinzler, K.W. (Accessed 2007). [http://www.ommbid.com The Online Metabolic and Molecular Bases of Inherited Disease]. New York: McGraw-Hill. - Summaries of 255 chapters, full text through many universities. There is also the [http://books.mcgraw-hill.com/medical/ommbid/blog/ OMMBID blog]. * For more online resources and references, see [[inborn errors of metabolism]]. {{AminoAcids}} [[Category:Proteinogenic amino acids]] [[Category:Glucogenic amino acids]] [[Category:Cyclic amino acids]] [[bn:প্রোলিন]] [[ca:Prolina]] [[cs:Prolin]] [[da:Prolin]] [[de:Prolin]] [[es:Prolina]] [[eo:Prolino]] [[fr:Proline]] [[ko:프롤린]] [[hr:Prolin]] [[id:Prolin]] [[it:Prolina]] [[he:פרולין]] [[lv:Prolīns]] [[lb:Prolin]] [[lt:Prolinas]] [[hu:Prolin]] [[nl:Proline]] [[ja:プロリン]] [[pl:Prolina]] [[pt:Prolina]] [[ru:Пролин]] [[fi:Proliini]] [[sv:Prolin]] [[tr:Prolin]] [[uk:Пролін]] [[zh:脯氨酸]]