Ghrelin can bind to a species of high density lipoprotein associated with paraoxonase.
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.
Beaumont
Nicholas J
NJ
Department of Biochemistry and Molecular Biology, Royal Free and University College Medical School, Rowland Hill Street, London NW3 2PF, United Kingdom. n.beaumont@rfc.ucl.ac.uk
Skinner
Vernon O
VO
Tan
Tricia M-M
TM
Ramesh
Bala S
BS
Byrne
Dominic J
DJ
MacColl
Gavin S
GS
Keen
Jeff N
JN
Bouloux
Pierre M
PM
Mikhailidis
Dimitri P
DP
Bruckdorfer
K Richard
KR
Vanderpump
Mark P
MP
Srai
Kaila S
KS
D043303:Aryldialkylphosphatase; D002499:Centrifugation, Density Gradient; D002846:Chromatography, Affinity; D002850:Chromatography, Gel; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D004950:Esterases / Q000737:chemistry / Q000378:metabolism*; D054439:Ghrelin; D013006:Growth Hormone / Q000378:metabolism; D006801:Humans; D008024:Ligands; D050356:Lipid Metabolism; D008075:Lipoproteins, HDL / Q000378:metabolism*; D010261:Paraoxon / Q000737:chemistry / Q000378:metabolism; D036361:Peptide Hormones / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D010949:Plasma / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013379:Substrate Specificity; D014461:Ultracentrifugation
D054439:Ghrelin; D008024:Ligands; D008075:Lipoproteins, HDL; D036361:Peptide Hormones; D010455:Peptides; C422650:ghrelin, des-n-octanoyl; D013006:Growth Hormone; D004950:Esterases; D043303:Aryldialkylphosphatase; D010261:Paraoxon