Proline

Jump to navigation Jump to search

Template:NatOrganicBox

WikiDoc Resources for Proline

Articles

Most recent articles on Proline

Most cited articles on Proline

Review articles on Proline

Articles on Proline in N Eng J Med, Lancet, BMJ

Media

Powerpoint slides on Proline

Images of Proline

Photos of Proline

Podcasts & MP3s on Proline

Videos on Proline

Evidence Based Medicine

Cochrane Collaboration on Proline

Bandolier on Proline

TRIP on Proline

Clinical Trials

Ongoing Trials on Proline at Clinical Trials.gov

Trial results on Proline

Clinical Trials on Proline at Google

Guidelines / Policies / Govt

US National Guidelines Clearinghouse on Proline

NICE Guidance on Proline

NHS PRODIGY Guidance

FDA on Proline

CDC on Proline

Books

Books on Proline

News

Proline in the news

Be alerted to news on Proline

News trends on Proline

Commentary

Blogs on Proline

Definitions

Definitions of Proline

Patient Resources / Community

Patient resources on Proline

Discussion groups on Proline

Patient Handouts on Proline

Directions to Hospitals Treating Proline

Risk calculators and risk factors for Proline

Healthcare Provider Resources

Symptoms of Proline

Causes & Risk Factors for Proline

Diagnostic studies for Proline

Treatment of Proline

Continuing Medical Education (CME)

CME Programs on Proline

International

Proline en Espanol

Proline en Francais

Business

Proline in the Marketplace

Patents on Proline

Experimental / Informatics

List of terms related to Proline

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Please Take Over This Page and Apply to be Editor-In-Chief for this topic: There can be one or more than one Editor-In-Chief. You may also apply to be an Associate Editor-In-Chief of one of the subtopics below. Please mail us [2] to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch.

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 humans can synthesize it. It is the unique proteogenic amino acid where the α-amino group is secondary.

Biosynthesis

Proline is biosynthetically derived from the amino acid L-glutamate and its immediate precursor is the imino acid (S)-Δ1-pyrroline-5-carboxylate (P5C). Enzymes involved in a typical biosynthesis include:[1]

  1. glutamate kinase (ATP-dependent)
  2. glutamate dehydrogenase (requires NADH or NADPH)
  3. 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 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 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, 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 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. 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.

Sequences of proline and 2-aminoisobutyric acid (Aib) also form a helical turn structure[citation needed].

In 2006, scientists at ASU discovered that solutions of 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.[2]

Cis-trans isomerization

Peptide bonds to proline and other N-substituted amino acids (such as sarcosine) are able to populate both the cis and trans isomers. Most peptide bonds prefer overwhelmingly to 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 both experience steric clashes with the neighboring subtitution and are nearly equally energetically disfavorable. 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 X, 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 prolines crucial for folding in the nonnative 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.

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 an ingredient in energy drinks such as "Sobe power fruit punch". [3] Proline has a sweet flavor with a distinct aftertaste.

See also

External links

Notes

  1. Nelson, D. L.; Cox, M. M. "Lehninger, Principles of Biochemistry" 3rd Ed. Worth Publishing: New York, 2000. ISNB 1-57259-153-6.
  2. B. J. Jones, M. J. Vergne, D. M. Bunk, L. E. Locascio and M. A. Hayes (2007). "Cleavage of Peptides and Proteins Using Light-Generated Radicals from Titanium Dioxide". Anal. Chem. 79 (4): 1327–1332. doi:10.1021/ac0613737.
  3. http://www.sobebev.com/product_info/powerline_power.shtml beverage has 25mg of Proline.

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). 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 OMMBID blog.
  • For more online resources and references, see inborn errors of metabolism.


Template:Biochemical families
Alanine (dp) | Arginine (dp) | Asparagine (dp) | Aspartic acid (dp) | Cysteine (dp) | Glutamic acid (dp) | Glutamine (dp) | Glycine (dp) | Histidine (dp) | Isoleucine (dp) | Leucine (dp) | Lysine (dp) | Methionine (dp) | Phenylalanine (dp) | Proline (dp) | Serine (dp) | Threonine (dp) | Tryptophan (dp) | Tyrosine (dp) | Valine (dp)

bn:প্রোলিন ca:Prolina da:Prolin de:Prolin eo:Prolino ko:프롤린 hr:Prolin id:Prolin it:Prolina he:פרולין lv:Prolīns lb:Prolin lt:Prolinas hu:Prolin nl:Proline fi:Proliini sv:Prolin uk:Пролін Template:SIB Template:Jb1 Template:WH Template:WS