Excretion of Hypusine by Children and by Patients with Familial Hyperlysinemia

Abstract

ExtractThree children with familial hyperlysinemia were found to excrete, respectively, 1,934 nmol/24 hr, 730 nmol/24 hr, and 1,121 nmol/24 hr hypusine and 16.1 mmol/24 hr, 7.0 mmol/24 hr, and 16.6 mmol/24 hr lysine. Ten juvenile control subjects excreted 35-253 nmol/24 hr (mean 156 nmol/24 hr) hypusine and 0.2-1.5 mmol/24 hr (mean 0.7 mmol/24 hr) lysine. Three infant control subjects were found to excrete 156 nmol/24 hr, 60 nmol/24 hr, and 77 nmol/24 hr hypusine. Serum levels of hypusine for subjects with hyperlysinemia were normal (less than 20 nmol/100 ml). SpeculationPatients with familial hyperlysinemia excrete both hypusine and lysine at levels 7-10 times higher than those observed for control subjects, while serum levels of hypusine in patients with hyperlysinemia are not elevated. These findings suggest that hypusine may be an endometabolite of lysine and not further metabolized or utilized.

Specific and sensitive GC–MS analysis of hypusine, Nε-(4-amino-2-hydroxybutyl)lysine, a biomarker of hypusinated eukaryotic initiation factor eIF5A, and its application to the bi-ethnic ASOS study

“…The creatinine-corrected concentration of endogenous Hyp corresponds to 0.286 nmol Hyp/ mmol creatinine in volunteer #1 and 0.186 nmol Hyp/ mmol creatinine in volunteer #2. The concentrations and the creatinine-corrected excretion rates of Hyp in the urine samples of the two volunteers lie in ranges reported previously using automated amino acid analyzers (Nakajima et al 1971;Woody and Pupene 1973). They are of the same order of magnitude reported by us for Lys metabolites generated by other post-translational modifications using a similar GC-MS methodology (Baskal et al 2021).…”

“…The same urine samples of the two above-mentioned volunteers were spiked with 0, 1, 2, 3, 4, and 5 µM of synthetic Hyp. These concentrations are considered relevant in human urine samples (Nakajima et al 1971 ; Woody and Pupene 1973 ). The concentration of the internal standard was set to 2.0 µM to cover the entire concentration range.…”

“…Children with hyperlysinemia were found to excrete 7-10 times higher amounts of free Hyp compared to controls (730-1934 vs. 37-271 nmol Hyp per 24 h), but to have serum concentrations of hypusine of about 200 nM, i.e., comparable to those of healthy controls (Woody and Pupene 1973). In the above-mentioned publications, Hyp has been analyzed by commercially available automatic amino acid analyzers without reporting the analytical performance of this technique (Nakajima et al 1971;Woody and Pupene 1973). These studies did not report on the occurrence of deoxyhypusine (N ε -(4-amino-butyl)lysine).…”

“…Healthy humans were found to excrete about 110 nmol Hyp per mmol creatinine (corresponding to concentrations of 1-5 µM in the urine); the serum Hyp concentration was reported to be below 200 nM (Nakajima et al 1971). Children with hyperlysinemia were found to excrete 7-10 times higher amounts of free Hyp compared to controls (730-1934 vs. 37-271 nmol Hyp per 24 h), but to have serum concentrations of hypusine of about 200 nM, i.e., comparable to those of healthy controls (Woody and Pupene 1973). In the above-mentioned publications, Hyp has been analyzed by commercially available automatic amino acid analyzers without reporting the analytical performance of this technique (Nakajima et al 1971;Woody and Pupene 1973).…”

Biochemistry and Function of Hypusine Formation on Eukaryotic Initiation Factor 5A

“…For example, we do not know why a high level of hypusine excretion occurs in patients with familial hyperlysinemia [12]. Nor do we know whether GABA-hypusine discovered in the brain [ 13] functions as a neurotransmitter.…”