Ghrelin Can Bind to a Species of High Density Lipoprotein Associated with Paraoxonase

• Published in: The Journal of biological chemistry Vol. 278; no. 11; pp. 8877 - 8880
• Main Authors: Beaumont, Nicholas J, Skinner, Vernon O, Tan, Tricia M-M, Ramesh, Bala S, Byrne, Dominic J, MacColl, Gavin S, Keen, Jeff N, Bouloux, Pierre M, Mikhailidis, Dimitri P, Bruckdorfer, K Richard, Vanderpump, Mark P, Srai, Kaila S
• Format: Journal Article
• Language: English
• Published: United States American Society for Biochemistry and Molecular Biology 14-03-2003
• Subjects: Aryldialkylphosphatase; Centrifugation, Density Gradient; Chromatography, Affinity; Chromatography, Gel; Dose-Response Relationship, Drug; Electrophoresis, Polyacrylamide Gel; Esterases - chemistry; Esterases - metabolism; Ghrelin; Growth Hormone - metabolism; Humans; Ligands; Lipid Metabolism; Lipoproteins, HDL - metabolism; Paraoxon - chemistry; Paraoxon - metabolism; Peptide Hormones - chemistry; Peptide Hormones - isolation & purification; Peptide Hormones - metabolism; Peptides - chemistry; Peptides - metabolism; Plasma - metabolism; Protein Binding; Protein Structure, Tertiary; Substrate Specificity; Ultracentrifugation
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.C200575200

Ghrelin is a 28-residue peptide hormone that is principally released from the stomach during fasting and prior to eating.
Two forms are present in human plasma: the unmodified peptide and a less abundant acylated version, in which octanoic acid
is attached to the third residue, a serine, via an ester linkage. The acylated form of ghrelin acts as a ligand for the growth
hormone secretagogue receptor and can stimulate the release of growth hormone from the pituitary gland. It also initiates
behavioral and metabolic adaptations to fasting. Here we show that an immobilized form of ghrelin specifically binds a species
of high density lipoprotein associated with the plasma esterase, paraoxonase, and clusterin. Both free ghrelin and paraoxon,
a substrate for paraoxonase, can inhibit this interaction. An endogenous species of ghrelin is found to co-purify with high
density lipoprotein during density gradient centrifugation and subsequent gel filtration. This interaction links the orexigenic
peptide hormone ghrelin to lipid transport and metabolism. Furthermore, the interaction of the esterified hormone ghrelin
with a species of HDL containing an esterase suggests a possible mechanism for the conversion of ghrelin to des-acyl ghrelin.