Screening of the amino acid hypusine molecular actions

Abstract

The amino acid hypusine was first identified in 1971 from bovine brain extract. Later, this amino acid was found in liver, kidney, muscle and blood of other mammals. In addition, hypusine is a substrate to synthesise the ±-(³-aminobutyryl)-hypusine (GABA-hypusine) dipeptide. The GABA is the most representative inhibitory neurotransmitter of the central nervous system. It is noted that the dipeptide GABA-hypusine has partial structural relationship with the dipeptide GABA-histidine (homocarnosine). Homocarnosine is widely studied and presents antioxidant, neurotransmitter and metal chelating activities, being considered an important modulator of neuronal excitability. The hypusine amino acid is formed from a post-translational modification that occurs at the eukaryotic translation initiation factor 5A (eIF5A) and the free form is derived from the degradation of this protein. The eIF5A protein is the only one described as having the amino acid residue hypusine, which is essential for its activity. In this context, although hypusine and GABA-hypusine were discovered in the 70's and 80's, respectively, their biological activities are still unknown. The present project aims to characterize the distribution of hypusine and GABA-hypusine in different tissues of mice and to evaluate the cellular effects of the amino acid hypusine in cerebral cells, aiming at the identification of potential biotechnological properties. (AU)