Peptide YY

Structure

Mature PYY is a linear peptide consisting of 36 aa residues in mammals and nonmammalian vertebrates, and both C- and N-terminal residues are tyrosine (Y), which is responsible for its name . C-terminal Y is amidated. PYY is a member of the neuropeptide Y (NPY) family, and its amino acid sequence similarity is ~70% with NPY, and 50% with the pancreatic polypeptide (PP). The aa sequences of PYY are conserved in mammals and in nonmammalian species. Two major molecular forms of PYY circulating in blood are PYY1–36 and PYY3–36.

Gene, mRNA, and precursor

The human PYY gene is localized on chromosome 17 (q21.31). The PYY gene transcript contains three exons. In humans, preproPYY has 97 aa residues, comprising a 28-aa signal peptide, a 36-aa mature PYY, and a 33-aa C-terminal peptide. Pyy mRNA is expressed in the epithelial cells of the jejunum, cecum, and colon in rats. In the rat brain, Pyy mRNA is distributed in the rostral brainstem.

Synthesis and release

A potential AP-1 binding site and several potential AP-2 binding sequences, which are activated by cAMP and phorbol ester, are located upstream of the transcriptional initiation site. PYY is synthesized in the enteroendocrine L cells in the distal ileal, colonic, and rectal mucosae. In the pancreas, PYY is coproduced with glucagon and PP. In the lower intestine, PYY is also synthesized in the same cells with glucagon. Dietary fat strongly stimulates PYY secretion into the bloodstream, and plasma PYY levels increase significantly within 15–30min after nutrient ingestion. Gastric bypass surgery elevates plasma PYY levels. Postprandial levels of PYY are lower in obese subjects compared with lean subjects.

Receptors

Five distinct NPY receptor subtypes have been cloned, namely Y1, Y2, Y4, Y5, and y6. Among these receptors, PYY preferentially binds to the Y2 receptor and, to a lesser extent, to the Y1 and Y5 receptors. The Y1, Y2, and Y5 receptor subtypes are seven transmembrane-spanning GPCRs. They are associated with a member of the Gi and Go family, and thus ligand binding results in the inhibition of adenylyl cyclase and cAMP production.

Biological functions

PYY inhibits stomach acid secretion, stomach emptying, and pancreatic exocrine secretion. PYY administration reduces appetite and weight gain in rodents and obese humans. In contrast, the administration of PYY into the CNS has a potent stimulatory effect on food intake, like NPY.

Clinical implications

The intravenous administration of PYY at physiological levels induces anorectic effects in both normal and obese subjects.

Description

Peptide YY is released postprandially from intestinal L cells as a satiety signal. In 1980, PYY was isolated and identified from the porcine intestine by means of a unique chemical assay identifying the C-terminal amide structure.

Uses

Peptide YY is a 36 amino acid gut hormone. The two main endogenous forms of Peptide YY have been linked to the development or maintenance of obesity.