Adipokinetic hormone

Adipokinetic hormone (AKH) is a short peptide hormone that has been studied in insects. It is a lipid mobilising hormone and is responsible for regulating fuel transport in the haemolymph, for redirecting energy to other processes as required by the insect.

AKH was initially discovered in the locusts Locusta migratoria and Schistocerca gregaria and is generally associated with aiding flight.[1] Early observations of locusts showed that despite the fact that lipids are metabolised by flight muscle in order to maintain flight, which would be transported from the haemolymph, there was often still a high concentration of lipids in the haemolymph, implying that an agent may be responsible for activating lipid transport into the haemolymph and this was thought most likely to be hormonal regulation.[2] The hormone itself is part of a larger family, often referred to as red pigment concentrating hormones (RPCH) discovered in crustaceans and the typical makeup of hormones in this family includes a length between 8 and 10 amino acids, blocked N and C termini, phenylalanine or tyrosine at position 4 and tryptophan at position 8.[3]

AKH has become an important area of study, particularly in insect crop pests and insects that act as intermediate or vector hosts for parasites that can affect humans or agricultural animals. It is believed that AKH does not only aid flight in insects, but it has also been shown that an increase in AKH can lead to stronger immune responses in locusts.[4][5] One group have performed experiments where locusts received an injection including AKH and lipopolysaccharide (LPS) – an immune elicitor found in the cell walls of bacteria – led to a stronger immune response than locusts which only received an LPS injection.[5]

The spread of malaria by the female mosquito, Anopheles gambiae, is dependent, amongst other things, on its ability to fly. This in turn, is 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 and hence NMR restrained molecular dynamics 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. Upon docking of the agonist 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. There is a close correspondence between the structure of the docked ligand and literature structure–activity studies. Information about the 3D structure and binding mode of Anoga-HrTH to its receptor is vital for the design of suitable mimetics which can act as insecticides.[6]

History of Adipokinetic Hormones (AKH)

AKH was first purified by an English group in 1976 and the chemical structure was determined to be a peptide hormone formed from 10 amino acids. This was the first instance where an insect peptide hormone had been identified.[2] Later, after AKH was identified in cockroaches, locust AKH was inserted into a cockroach and a similar increase in lipid mobilisation was observed. Conversely, cockroach AKH led to similar activity within a locust.[2]

History of Red pigment-concentrating hormones (RPCH)

RPCH was discovered in crustaceans and shown to be involved in concentrating red pigments, for sexual displays and a variety of other reasons. The similarity between AKH and RPCH is so significant that injecting insects with RPCH induces an AKH like response and vice versa [7] In 1972 the complete structure of the first invertebrate neuropeptide was published.The peptide was isolated from the eyestalks of the prawn Pandalus borealis. Its function is to concentrate red pigment granules in epithelial chromatophores,thus effecting color change of the body integument. Accordingly,it is called red pigment-concentrating hormone(today denoted as Panbo-RPCH). This octapeptide is a member of the large adipokineti chormone AKH/RPCH family which occurs mainly,but not exclusively in the two sister groups,insects and crustaceans. The family is characterized by octa- ,nona- or deca- peptides with characteristic aromatic amino acids at positions 4and 8 as well as post-translationally modified N-(pyroglutamate) and C-termini (amidation).

References
  1. Stone, J.V., Mordue, W., Batley, K.E. and Morris, H.R., Structure of locust adipokinetic hormone, a neurohormone that regulates lipid utilisation during flight. Nature, 1976. 263(5574): p.207-211.
  2. Chapter Eleven Archived June 7, 2008, at the Wayback Machine
  3. Stone, J.V. Mordue, W. Batley, K.E. Morris, H.R., Structure of locust adipokinetic hormone, a neurohormone that regulates lipid utilisation during flight
  4. 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
  5. 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
  6. 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.
  7. Dallman et al. Adipokinetic activity of shrimp and locust peptide hormones in butterflies. General and Comparative Endocrinology, 1981. 43(2): p. 256-258.
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