Jump to content

Peptide YY

From Wikipedia, the free encyclopedia
Not to be confused withNeuropeptide Y.
Not to be confused withPancreatic polypeptide.
"PYY" redirects here. For the IATA code PYY, seePai Airport.
PYY
Available structures
PDBOrtholog search:PDBeRCSB
Identifiers
AliasesPYY,PYY-I, PYY1, peptide YY
External IDsOMIM:600781;MGI:99924;HomoloGene:3066;GeneCards:PYY;OMA:PYY - orthologs
Orthologs
SpeciesHumanMouse
Entrez

5697

217212

Ensembl

ENSG00000131096

ENSMUSG00000017311

UniProt

P10082

Q9EPS2

RefSeq (mRNA)

NM_004160
NM_001394028
NM_001394029

NM_145435
NM_001346771

RefSeq (protein)

NP_004151

NP_001333700
NP_663410

Location (UCSC)Chr 17: 43.95 – 44 MbChr 11: 102 – 102 Mb
PubMedsearch[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Peptide YY(PYY), also known aspeptide tyrosine tyrosine,is a peptide that in humans is encoded by thePYYgene.[5]Peptide YY is a short (36-amino acid) peptide released from cells in theileumandcolonin 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 alsoanorexigenic,i.e., it reduces appetite.[6]

Dietary fibersfrom fruits, vegetables, and whole grains, consumed, increase the speed of transit of intestinalchymeinto theileum,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.[7]

Structure

[edit]

Peptide YY is related to thepancreatic peptidefamily by having 18 of its 36 amino acids located in the same positions as pancreatic peptide.[8]The two major forms of peptide YY are PYY1-36and PYY3-36,which have PP fold structural motifs. However, the most common form of circulating PYY immunoreactivity is PYY3-36,which binds to theY2receptor (Y2R)of theY familyof receptors.[9]Peptide YY3-36(PYY) is a linearpolypeptideconsisting of 34amino acidswith structuralhomologytoNPYandpancreatic 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.[10]

Release

[edit]

PYY is found inL cellsin themucosaofgastrointestinal tract,especially inileumandcolon.Also, a small amount of PYY, about 1-10%, is found in theesophagus,stomach,duodenumandjejunum.[11]PYY concentration in the circulation increases postprandially (after food ingestion) and decreases byfasting.[9]In addition, PYY is produced by a discrete population of neurons in thebrainstem,specifically localized to thegigantocellular reticular nucleusof themedulla oblongata.[12]C. R. Gustavsenet al.had found PYY-producing cells located in theislets of Langerhansin rats. They were observed either alone or co-localized with glucagon or PP.[13]

PYY is released by the L-cells of the gastrointestinal tract following food intake, and there are two main endogenous forms: PYY1-36and PYY3-36.PYY1-36is rapidly processed by the enzymeDPP4to the 34-amino acid peptide PYY3-36.<[14]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, PYY3-36has a high selectivity for theY2-receptor,compared to PYY1-36which 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 PYY3-36on any other Y receptor other than Y2.[15]Other studies replacing the amide bonds with ester bonds also confirm that the end section is important in binding and activation.[16]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.[17]As a result of this, the Y2 receptor is considered a target for the treatment of obesity and type II diabetes.

Function

[edit]

PYY exerts its action throughNPY receptors;it inhibitsgastric motilityand increases water andelectrolyteabsorption in the colon.[18]PYY may also suppresspancreaticsecretion.It is secreted by theneuroendocrine cellsin theileumandcolonin response to a meal, and has been shown to reduceappetite.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 removingaluminiumaccumulated in thebrain.[citation needed]

Animal studies

[edit]

Several studies have shown acute peripheral administration of PYY3-36inhibits feeding of rodents and primates. Other studies onY2R-knockout micehave shown noanorecticeffect on them. These findings indicate PYY3-36has 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 toobesity,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.[9]PYY oral spray was found to promote fullness.[19]Viral gene therapy of the salivary glands resulted in long-term intake reduction.[20]

Relevance to obesity

[edit]

Leptinalso reduces appetite in response to feeding, butobesepeople develop a resistance to leptin. Obese people secrete less PYY than non-obese people,[21]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).[22]

While some studies have shown obese persons have lower circulating level of PYY postprandially, other studies have reported they have normal sensitivity to theanorecticeffect 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.[9]

The consumption of protein boosts PYY levels, so some benefit was observed in experimental subjects in reducing hunger and promoting weight loss.[23]This could partially explain the weight-loss experienced withhigh-protein diets,noting also the highthermic 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 enhancedGLP-1responsiveness. Insulin sensitivity improves in proportion to weight loss, with a possible involvement of PYY.[24]

See also

[edit]

References

[edit]

This article incorporatestextby Jessica Hutchinson available under theCC BY 3.0license.

  1. ^abcGRCh38: Ensembl release 89: ENSG00000131096–Ensembl,May 2017
  2. ^abcGRCm38: Ensembl release 89: ENSMUSG00000017311–Ensembl,May 2017
  3. ^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^"Mouse PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^EntrezGene5697
  6. ^Woods SC, D'Alessio DA (November 2008)."Central control of body weight and appetite".The Journal of Clinical Endocrinology and Metabolism.93(11 Suppl 1): S37–S50.doi:10.1210/jc.2008-1630.PMC2585760.PMID18987269.
  7. ^Murashita K, Kurokawa T, Nilsen TO, Rønnestad I (February 2009). "Ghrelin, cholecystokinin, and peptide YY in Atlantic salmon (Salmo salar): molecular cloning and tissue expression".General and Comparative Endocrinology.160(3): 223–235.doi:10.1016/j.ygcen.2008.11.024.PMID19073185.
  8. ^DeGroot LJ (1989). McGuigan JE (ed.).Endocrinology.Philadelphia: Saunders. p.2754.ISBN978-0-7216-2888-2.
  9. ^abcdMurphy KG, Bloom SR (December 2006). "Gut hormones and the regulation of energy homeostasis".Nature.444(7121): 854–859.Bibcode:2006Natur.444..854M.doi:10.1038/nature05484.PMID17167473.S2CID1120344.
  10. ^Tatemoto K (April 1982)."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.Bibcode:1982PNAS...79.2514T.doi:10.1073/pnas.79.8.2514.PMC346229.PMID6953409.
  11. ^Taylor IL (March 1985). "Distribution and release of peptide YY in dog measured by specific radioimmunoassay".Gastroenterology.88(3): 731–737.doi:10.1016/0016-5085(85)90144-1.PMID3838162.
  12. ^Glavas MM, Grayson BE, Allen SE, Copp DR, Smith MS, Cowley MA, Grove KL (January 2008). "Characterization of brainstem peptide YY (PYY) neurons".The Journal of Comparative Neurology.506(2): 194–210.doi:10.1002/cne.21543.PMID18022952.S2CID16104580.
  13. ^Gustavsen CR, Pillay N, Heller RS (2008). "An immunohistochemical study of the endocrine pancreas of the African ice rat, Otomys sloggetti robertsi".Acta Histochemica.110(4): 294–301.doi:10.1016/j.acthis.2007.11.003.PMID18406449.
  14. ^Ehrlich GK, Michel H, Truitt T, Riboulet W, Pop-Damkov P, Goelzer P, Hainzl D, Qureshi F, Lueckel B, Danho W, Conde-Knape K, Konkar A (December 2013). "Preparation and characterization of albumin conjugates of a truncated peptide YY analogue for half-life extension".Bioconjugate Chemistry.24(12): 2015–24.doi:10.1021/bc400340z.PMID24251972.
  15. ^Nygaard R, Nielbo S, Schwartz TW, Poulsen FM (July 2006). "The PP-fold solution structure of human polypeptide YY and human PYY3-36 as determined by NMR".Biochemistry.45(27): 8350–7.doi:10.1021/bi060359l.PMID16819834.
  16. ^Albertsen L, Andersen JJ, Paulsson JF, Thomsen JK, Norrild JC, Strømgaard K (December 2013)."Design and Synthesis of Peptide YY Analogues with C-terminal Backbone Amide-to-Ester Modifications".ACS Medicinal Chemistry Letters.4(12): 1228–32.doi:10.1021/ml400335g.PMC4027376.PMID24900634.
  17. ^Keire DA, Bowers CW, Solomon TE, Reeve JR (February 2002). "Structure and receptor binding of PYY analogs".Peptides.23(2): 305–21.doi:10.1016/s0196-9781(01)00602-7.PMID11825645.S2CID7082920.
  18. ^Liu CD, Aloia T, Adrian TE, Newton TR, Bilchik AJ, Zinner MJ, et al. (March 1996). "Peptide YY: a potential proabsorptive hormone for the treatment of malabsorptive disorders".The American Surgeon.62(3): 232–236.PMID8607584.
  19. ^"UF researchers use oral peptide spray to stimulate weight loss in animals".Dec 19, 2013.
  20. ^Acosta A, Hurtado MD, Gorbatyuk O, La Sala M, Duncan D, Aslanidi G, et al. (2011)."Salivary PYY: a putative bypass to satiety".PLOS ONE.6(10): e26137.Bibcode:2011PLoSO...626137A.doi:10.1371/journal.pone.0026137.PMC3189958.PMID22028819.
  21. ^Alvarez Bartolomé M, Borque M, Martinez-Sarmiento J, Aparicio E, Hernández C, Cabrerizo L, Fernández-Represa JA (June 2002). "Peptide YY secretion in morbidly obese patients before and after vertical banded gastroplasty".Obesity Surgery.12(3): 324–327.doi:10.1381/096089202321088084.PMID12082881.S2CID40358403.
  22. ^Batterham RL, Cohen MA, Ellis SM, Le Roux CW, Withers DJ, Frost GS, et al. (September 2003)."Inhibition of food intake in obese subjects by peptide YY3-36".The New England Journal of Medicine.349(10): 941–948.doi:10.1056/NEJMoa030204.PMID12954742.S2CID11764433.
  23. ^Batterham RL, Heffron H, Kapoor S, Chivers JE, Chandarana K, Herzog H, et al. (September 2006)."Critical role for peptide YY in protein-mediated satiation and body-weight regulation".Cell Metabolism.4(3): 223–233.doi:10.1016/j.cmet.2006.08.001.PMID16950139.
  24. ^Nannipieri M, Baldi S, Mari A, Colligiani D, Guarino D, Camastra S, et al. (November 2013)."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.doi:10.1210/jc.2013-2538.PMID24057293.

Further reading

[edit]
[edit]
Retrieved from "https://en.wikipedia.org/w/index.php?title=Peptide_YY&oldid=1217204871"