Biology:Peptide YY

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Short description: Peptide released from cells in the ileum and colon in response to feeding
Not to be confused with Neuropeptide Y.
A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

Peptide YY (PYY) also known as peptide tyrosine tyrosine is a peptide that in humans is encoded by the PYY gene.[1] Peptide YY is a short (36-amino acid) peptide released from cells in the ileum and colon in response to feeding. In the blood, gut, and other elements of periphery, PYY acts to reduce appetite; similarly, when injected directly into the central nervous system, PYY is also anorexigenic, i.e., it reduces appetite.[2]

Dietary fibers from fruits, vegetables, and whole grains, consumed, increase the speed of transit of intestinal chyme into the ileum, to raise PYY3-36, and induce satiety. Peptide YY cannot be produced as the result of enzymatic breakdown of crude fish proteins and ingested as a food product.[3]

Structure

Peptide YY is related to the pancreatic peptide family by having 18 of its 36 amino acids located in the same positions as pancreatic peptide.[4] The two major forms of peptide YY are PYY1-36 and PYY3-36, which have PP fold structural motifs. However, the most common form of circulating PYY immunoreactivity is PYY3-36, which binds to the Y2 receptor (Y2R) of the Y family of receptors.[5] Peptide YY3-36 (PYY) is a linear polypeptide consisting of 34 amino acids with structural homology to NPY and pancreatic polypeptide.

The PP-fold motif is found throughout this family and relates to the 3D structure. The PP-fold is formed through the incorporation of certain residues which are predominately Pro2, Pro5, Pro8, Gly9, Tyr20 and Tyr27. This PP-fold has been found to protect the peptide against enzymatic attack as well as producing a hydrophobic pocket which is inherently overall energy reducing. In addition to containing the PP-fold motif, PYY and its derivative PYY3- 36 also have a high C-terminal α-helix proportion, suggested to be extremely important for the structural integrity of PYY.[6]

Release

PYY is found in L cells in the mucosa of gastrointestinal tract, especially in ileum and colon. Also, a small amount of PYY, about 1-10%, is found in the esophagus, stomach, duodenum and jejunum.[7] PYY concentration in the circulation increases postprandially (after food ingestion) and decreases by fasting.[5] In addition, PYY is produced by a discrete population of neurons in the brainstem, specifically localized to the gigantocellular reticular nucleus of the medulla oblongata.[8] C. R. Gustavsen et al. had found PYY-producing cells located in the islets of Langerhans in rats. They were observed either alone or co-localized with glucagon or PP.[9]

PYY is released by the L-cells of the gastrointestinal tract following food intake, and there are two main endogenous forms: PYY1-36 and PYY3-36. PYY1-36 is rapidly processed by the enzyme DPP4 to the 34-amino acid peptide PYY3-36.<[10] DPP4 hydrolyses PYY and removes the first two amino acids, tyrosine and proline, at the N-terminal, which changes the receptor selectivity. As a result of this, PYY3-36 has a high selectivity for the Y2-receptor, compared to PYY1-36 which has selectivity for the Y1, Y2, and Y5 receptors. It is thought that the Y1 receptor requires both the C-terminus and N-terminus for recognition, binding and then subsequent activation. The Y2 receptor is thought to have a smaller receptor site and also only requires the C-terminus for recognition.

This could explain the reduced affinity for PYY3-36 on any other Y receptor other than Y2.[11] Other studies replacing the amide bonds with ester bonds also confirm that the end section is important in binding and activation.[12] The Y2 receptors are located in the hippocampus, sympathetic and parasympathetic nerve fibres, intestines, and certain blood vessels, and have been implicated in regulating food intake and gastric emptying.[13] As a result of this, the Y2 receptor is considered a target for the treatment of obesity and type II diabetes.

Function

PYY exerts its action through NPY receptors; it inhibits gastric motility and increases water and electrolyte absorption in the colon.[14] PYY may also suppress pancreatic secretion. It is secreted by the neuroendocrine cells in the ileum and colon in response to a meal, and has been shown to reduce appetite. PYY works by slowing the gastric emptying; hence, it increases efficiency of digestion and nutrient absorption after a meal. Research has also indicated PYY may be useful in removing aluminium accumulated in the brain.[citation needed]

Animal studies

Several studies have shown acute peripheral administration of PYY3-36 inhibits feeding of rodents and primates. Other studies on Y2R-knockout mice have shown no anorectic effect on them. These findings indicate PYY3-36 has an anorectic (losing appetite) effect, which is suggested to be mediated by Y2R. PYY-knockout female mice increase in body weight and fat mass. PYY-knockout mice, on the other hand, are resistant to obesity, but have higher fat mass and lower glucose tolerance when fed a high-fat diet, compared to control mice. Thus, PYY also plays a very important role in energy homeostasis by balancing food intake.[5] PYY oral spray was found to promote fullness.[15] Viral gene therapy of the salivary glands resulted in long-term intake reduction.[16]

Relevance to obesity

Leptin also reduces appetite in response to feeding, but obese people develop a resistance to leptin. Obese people secrete less PYY than non-obese people,[17] and attempts to use PYY directly as a weight-loss drug have met with some success. Researchers noted the caloric intake during a buffet lunch offered two hours after the infusion of PYY was decreased by 30% in obese subjects (p < 0.001) and 31% in lean subjects (p < 0.001).[18]

While some studies have shown obese persons have lower circulating level of PYY postprandially, other studies have reported they have normal sensitivity to the anorectic effect of PYY3-36. Thus, reduction in PYY sensitivity may not be one of the causes of obesity, in contrast to the reduction of leptin sensitivity. The anorectic effect of PYY could possibly be a future obesity drug.[5]

The consumption of protein boosts PYY levels, so some benefit was observed in experimental subjects in reducing hunger and promoting weight loss.[19] This could partially explain the weight-loss experienced with high-protein diets, noting also the high thermic effect of protein.

Obese patients undergoing gastric bypass showed marked metabolic adaptations, resulting in frequent diabetes remission 1 year later. When the confounding of calorie restriction is factored out, β-cell function improves rapidly, very possibly under the influence of enhanced GLP-1 responsiveness. Insulin sensitivity improves in proportion to weight loss, with a possible involvement of PYY.[20]

See also

References

  1. ↑ EntrezGene 5697
  2. ↑ "Central control of body weight and appetite". The Journal of Clinical Endocrinology and Metabolism 93 (11 Suppl 1): S37–S50. November 2008. doi:10.1210/jc.2008-1630. PMID 18987269. 
  3. ↑ "Ghrelin, cholecystokinin, and peptide YY in Atlantic salmon (Salmo salar): molecular cloning and tissue expression". General and Comparative Endocrinology 160 (3): 223–235. February 2009. doi:10.1016/j.ygcen.2008.11.024. PMID 19073185. 
  4. ↑ Endocrinology. Philadelphia: Saunders. 1989. p. 2754. ISBN 978-0-7216-2888-2. https://archive.org/details/endocrinology0002unse/page/2754. 
  5. ↑ 5.0 5.1 5.2 5.3 "Gut hormones and the regulation of energy homeostasis". Nature 444 (7121): 854–859. December 2006. doi:10.1038/nature05484. PMID 17167473. Bibcode: 2006Natur.444..854M. 
  6. ↑ "Isolation and characterization of peptide YY (PYY), a candidate gut hormone that inhibits pancreatic exocrine secretion". Proceedings of the National Academy of Sciences of the United States of America 79 (8): 2514–8. April 1982. doi:10.1073/pnas.79.8.2514. PMID 6953409. Bibcode: 1982PNAS...79.2514T. 
  7. ↑ "Distribution and release of peptide YY in dog measured by specific radioimmunoassay". Gastroenterology 88 (3): 731–737. March 1985. doi:10.1016/0016-5085(85)90144-1. PMID 3838162. 
  8. ↑ "Characterization of brainstem peptide YY (PYY) neurons". The Journal of Comparative Neurology 506 (2): 194–210. January 2008. doi:10.1002/cne.21543. PMID 18022952. 
  9. ↑ "An immunohistochemical study of the endocrine pancreas of the African ice rat, Otomys sloggetti robertsi". Acta Histochemica 110 (4): 294–301. 2008. doi:10.1016/j.acthis.2007.11.003. PMID 18406449. 
  10. ↑ "Preparation and characterization of albumin conjugates of a truncated peptide YY analogue for half-life extension". Bioconjugate Chemistry 24 (12): 2015–24. December 2013. doi:10.1021/bc400340z. PMID 24251972. 
  11. ↑ "The PP-fold solution structure of human polypeptide YY and human PYY3-36 as determined by NMR". Biochemistry 45 (27): 8350–7. July 2006. doi:10.1021/bi060359l. PMID 16819834. 
  12. ↑ "Design and Synthesis of Peptide YY Analogues with C-terminal Backbone Amide-to-Ester Modifications". ACS Medicinal Chemistry Letters 4 (12): 1228–32. December 2013. doi:10.1021/ml400335g. PMID 24900634. 
  13. ↑ "Structure and receptor binding of PYY analogs". Peptides 23 (2): 305–21. February 2002. doi:10.1016/s0196-9781(01)00602-7. PMID 11825645. 
  14. ↑ "Peptide YY: a potential proabsorptive hormone for the treatment of malabsorptive disorders". The American Surgeon 62 (3): 232–236. March 1996. PMID 8607584. 
  15. ↑ "UF researchers use oral peptide spray to stimulate weight loss in animals". Dec 19, 2013. http://news.ufl.edu/archive/2013/12/uf-researchers-use-oral-peptide-spray-to-stimulate-weight-loss-in-animals.html. 
  16. ↑ "Salivary PYY: a putative bypass to satiety". PLOS ONE 6 (10): e26137. 2011. doi:10.1371/journal.pone.0026137. PMID 22028819. Bibcode: 2011PLoSO...626137A. 
  17. ↑ "Peptide YY secretion in morbidly obese patients before and after vertical banded gastroplasty". Obesity Surgery 12 (3): 324–327. June 2002. doi:10.1381/096089202321088084. PMID 12082881. 
  18. ↑ "Inhibition of food intake in obese subjects by peptide YY3-36". The New England Journal of Medicine 349 (10): 941–948. September 2003. doi:10.1056/NEJMoa030204. PMID 12954742. https://discovery.ucl.ac.uk/id/eprint/8671/. 
  19. ↑ "Critical role for peptide YY in protein-mediated satiation and body-weight regulation". Cell Metabolism 4 (3): 223–233. September 2006. doi:10.1016/j.cmet.2006.08.001. PMID 16950139. 
  20. ↑ "Roux-en-Y gastric bypass and sleeve gastrectomy: mechanisms of diabetes remission and role of gut hormones". The Journal of Clinical Endocrinology and Metabolism 98 (11): 4391–4399. November 2013. doi:10.1210/jc.2013-2538. PMID 24057293. 

Further reading

External links



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