Identification of the acyltransferase that octanoylates ghrelin, an appetite-stimulating peptide hormone

  • 0Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

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Summary

This summary is machine-generated.

Scientists discovered Ghrelin O-Acyltransferase (GOAT), an enzyme essential for activating the appetite-stimulating hormone ghrelin. This finding may lead to new obesity treatments by targeting GOAT to reduce appetite.

Area Of Science

  • Biochemistry
  • Endocrinology
  • Molecular Biology

Background

  • Ghrelin, an appetite-stimulating peptide hormone, requires acylation at Serine-3 for its endocrine functions.
  • This acylation involves attachment of an eight-carbon fatty acid, octanoate.

Purpose Of The Study

  • To identify the enzyme responsible for the octanoylation of ghrelin.
  • To characterize the identified enzyme and its role in ghrelin activation.

Main Methods

  • Genome analysis to identify potential acyltransferase candidates.
  • Coexpression of candidate enzymes with prepro-ghrelin in cultured endocrine cells.
  • Assay of GOAT activity and identification of conserved catalytic residues.

Main Results

  • Ghrelin O-Acyltransferase (GOAT) was identified as the enzyme that octanoylates ghrelin at Serine-3.
  • GOAT is a polytopic membrane-bound enzyme belonging to a family of acyltransferases.
  • GOAT activity depends on conserved catalytic residues (asparagine and histidine).
  • GOAT mRNA expression is primarily localized in the stomach and intestine.

Conclusions

  • GOAT is the specific enzyme responsible for ghrelin octanoylation.
  • The identification of GOAT provides a target for developing therapies to manage appetite and obesity.

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