Adipokinetic hormones (AKHs) are metabolic
neuropeptides, mediating mobilization of energy substrates in many insects.
History
An English group first purified AKH in 1976. The chemical structure was determined to be a
peptide hormone formed from 10
amino acids. This was the first insect peptide hormone to be identified.[1] After AKH was identified in
cockroaches,
locust AKH was inserted into a cockroach. A similar increase in
lipid mobilization was observed. Conversely, cockroach AKH led to similar activity within a locust.[1]
AKH was initially discovered in the locusts Locusta migratoria and Schistocerca gregaria. It is generally associated with aiding flight.[2] Lipids are transported from the
hemolymph and metabolized by flight muscle in order to maintain flight. However, a high concentration of lipids remains in the hemolymph, implying that an agent may be responsible for activating lipid transport into the hemolymph. This was thought most likely to be a function of
hormonal regulation.[1] The hormone itself is part of a larger family, often referred to as red pigment concentrating hormones (RPCH) discovered in
crustaceans.
AKH has become an important area of study, particularly in insect crop
pests and insects that act as intermediate or
vectorhosts for parasites that can affect humans or animals. In experiments where locusts were injected with AKH and
lipopolysaccharide (LPS–an immune elicitor found in the cell walls of bacteria) a stronger immune response was observed than in locusts that only received an LPS injection.[8][9]
The spread of
malaria by the female mosquito, Anopheles gambiae, is partly dependent on the adipokinetic hormone, Anoga-HrTH (pGlu-Leu-Thr-Phe-Thr-Pro-Ala-Trp-NH2). No crystal structure of this important
neuropeptide is available. The
NMR restrained molecular dynamic was used to investigate its conformational space in aqueous solution and when bound to a membrane surface. The results showed that Anoga-HrTH has an almost cyclic conformation that is stabilized by a hydrogen bond between the C-terminus and Thr3. When the agonist docks to its receptor, this H-bond is broken and the molecule adopts a more extended structure. Preliminary AKHR docking calculations give the free energy of binding to be −47.30 kJ/mol. Information about the 3D structure and binding mode of Anoga-HrTH to its receptor are vital for the design of suitable mimetics which can act as insecticides.[10]
^König, Simone; Bayer, Malte; Marco, Heather; Gäde, Gerd (July 2019). "The hypertrehalosaemic neuropeptide conformational twins of cicadas consist of only l-amino acids: are they cis–trans isomers?". Amino Acids. 51 (7): 1023–1028.
doi:
10.1007/s00726-019-02742-1.
PMID31073692.
S2CID254074930.
^Goldsworthy, G., K. Opoku-Ware, and L. Mullen, Adipokinetic hormone enhances laminarin and bacterial lipopolysaccharide-induced activation of the prophenoloxidase cascade in the African migratory locust Locusta migratoria. Journal of Insect Physiology, 2002. 48: p. 601-608
^Goldsworthy, G.J., K. Opoku-Ware, and L.M. Mullen, Adipokinetic hormone and the immune responses of locusts to infection. Annals of the New York Academy of Science, 2005. 1040: p. 106-113
^Mugumbate G, Jackson GE, van der Spoel D, Kövér KE, Szilágyi L. Anopheles gambiae, Anoga-HrTH hormone, free and bound structure--a nuclear magnetic resonance experiment. Peptides. 2013 Mar;41:94-100. DOI: 10.1016/j.peptides.2013.01.008.