Structure-activity studies on adipokinetic hormones in Manduca sexta

Area of Science:

• Biochemistry
• Insect Physiology
• Endocrinology

Background:

• Adipokinetic hormone (AKH) is a crucial peptide hormone regulating lipid and carbohydrate metabolism in insects.
• The red pigment concentrating hormone (RPCH)/AKH family comprises structurally related peptides involved in metabolic regulation.

Purpose of the Study:

• To investigate the structure-activity relationships of adipokinetic hormone (AKH) in the insect Manduca sexta.
• To identify key structural features of AKH peptides essential for activating glycogen phosphorylase in M. sexta larvae.

Main Methods:

• Tested seven naturally occurring and four synthetic RPCH/AKH family peptides in Manduca sexta larvae.
• Assessed the activation of glycogen phosphorylase in the fat body of M. sexta larvae upon peptide administration.

Main Results:

• The N-terminal pyroglutamate (pGlu) is critical for peptide activity, though a modified N-terminus (AcGly1AKH) showed partial activity.
• Amino acid substitutions generally reduced peptide binding to the receptor, indicating the importance of specific residues.
• Peptide length was important, with ten-amino acid peptides demonstrating higher activity than shorter analogues.
• A beta-bend structure was not found to be essential for peptide binding in M. sexta.

Conclusions:

• Specific amino acid residues and N-terminal modifications significantly impact AKH activity in Manduca sexta.
• Peptide length and the presence of pGlu are critical determinants for AKH receptor interaction and metabolic function.
• These findings provide insights into the molecular basis of AKH signaling and its role in insect energy metabolism.