Chemical Identity

Property	Value
Chemical Formula	C149H249N47O42S
Molecular Weight	3370 Da
CAS Number	258279-04-8
Peptide Class	Octanoylated Peptide Hormone (28 aa)
Sequence	GSSFLSPEHQRVQQRKESKKPPAKLQPR
Modification	Ser3 octanoylation (n-octanoic acid)

Structure

Ghrelin is a 28-amino acid peptide hormone primarily produced by X/A-like cells in the gastric fundus. It has a unique octanoyl (C8:0) modification on serine at position 3, catalyzed by ghrelin O-acyltransferase (GOAT). This acylation is essential for biological activity and receptor binding.

Mechanism of Action

Octanoylated ghrelin binds the growth hormone secretagogue receptor (GHS-R1a), stimulating GH release from pituitary somatotrophs and activating hypothalamic appetite circuits (AgRP/NPY neurons). It promotes food intake, adipogenesis, and gastric motility. Des-acyl ghrelin (without octanoylation) has distinct metabolic effects.

Clinical Applications

• Appetite regulation: Primary endogenous orexigenic hormone
• GH release: Synergizes with GHRH for pulsatile GH secretion
• Cachexia: Therapeutic target in cancer and chronic disease cachexia
• Obesity: Ghrelin levels suppressed in obesity, elevated after weight loss
• Gastroparesis: Promotes gastric motility

Pharmacology

• Half-life: 27-31 minutes (acylated)
• Peak: Preprandial rise, postprandial fall
• Source: 80% from stomach
• GOAT: Essential enzyme for activation
• Levels: Elevated by fasting, sleep deprivation, stress

References

• Kojima, M., et al. (1999). Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature, 402, 656-660.
• Cummings, D.E., et al. (2002). Plasma ghrelin levels after diet-induced weight loss. New England Journal of Medicine, 346, 1623-1630.