Hyperlysinemia Without Clinical Findings

Ozalp, I; Hasanoğlu, Alev; Tuncbjlek, E.; Yalaz, Kalbiye

doi:10.1111/j.1651-2227.1981.tb06259.x

Cited by 14 publications

(12 citation statements)

References 13 publications

(3 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is consistent with competitive inhibition of the dibasic amino acid transporters SLC7A7 and SLC7A9/SLC3A1 in kidney by the high urine lysine levels leading to an amino aciduria that biochemically resembles a combination of lysinuric protein intolerance and cystinuria. 20,29 3.6 | Glutaric acid accumulation in Gcdh KO brain is decreased in Gcdh/Aass double KO mice Global metabolic profiles were determined in brain samples from all four groups of mice (Figure 4, Table S3). Glutaric acid levels were increased 181-fold in Gcdh KO brain when compared to controls.…”

Section: Other Selected Plasma and Urine Metabolitesmentioning

confidence: 99%

Deletion of 2‐aminoadipic semialdehyde synthase limits metabolite accumulation in cell and mouse models for glutaric aciduria type 1

Leandro

Dodatko

DeVita

et al. 2020

J of Inher Metab Disea

View full text Add to dashboard Cite

Glutaric aciduria type 1 (GA1) is an inborn error of lysine degradation characterized by acute encephalopathy that is caused by toxic accumulation of lysine degradation intermediates. We investigated the efficacy of substrate reduction through inhibition of 2-aminoadipic semialdehyde synthase (AASS), an enzyme upstream of the defective glutaryl-CoA dehydrogenase (GCDH), in a cell line and mouse model of GA1. We show that loss of AASS function in GCDH-deficient HEK-293 cells leads to an approximately fivefold reduction in the established GA1 clinical biomarker glutarylcarnitine. In the GA1 mouse model, deletion of Aass leads to a 4.3-, 3.8-, and 3.2-fold decrease in the glutaric acid levels in urine, brain, and liver, respectively. Parallel decreases were observed in urine and brain 3-hydroxyglutaric acid levels, and plasma, urine, and brain glutarylcarnitine levels. These in vivo data demonstrate that the saccharopine pathway is the main source of glutaric acid production in the brain and periphery of a mouse model for GA1, and support the notion that pharmacological inhibition of AASS may represent an attractive strategy to treat GA1.

show abstract

Section: Other Selected Plasma and Urine Metabolitesmentioning

confidence: 99%

Deletion of 2‐aminoadipic semialdehyde synthase limits metabolite accumulation in cell and mouse models for glutaric aciduria type 1

Leandro

Dodatko

DeVita

et al. 2020

J of Inher Metab Disea

View full text Add to dashboard Cite

show abstract

“…These enzyme activities are reduced to less than 10% in FH, resulting in hyperlysinemia (1.7 mM) and lysinuria with mild saccharopinuria. The disorder was first reported in individuals with physical and mental retardation (Woody, 1964; Ghadimi et al, 1965; Armstrong and Robinow, 1967) but further studies identified increases of Lys in blood of normal individuals, suggesting that hyperlysinemia alone may not be associated with a clinical phenotype (Ozalp et al, 1981). Therefore, it was postulated that the clinical feature found in the first patients diagnosed with FH may have reflected the method of case detection rather than damage as a result of the metabolic defect.…”

Section: Introductionmentioning

confidence: 99%

Lysine induces lipid and protein damage and decreases reduced glutathione concentrations in brain of young rats

Seminotti

Leipnitz

Amaral

et al. 2008

Intl J of Devlp Neuroscience

View full text Add to dashboard Cite

The present work investigated the in vitro effects of lysine on important parameters of oxidative stress in cerebral cortex of young rats. Our results show that lysine significantly induced lipid peroxidation, as determined by increase of thiobarbituric acid-reactive substances and chemiluminescence levels, as well as protein oxidative damage since carbonyl formation and sulfhydryl oxidation were enhanced by this amino acid. Furthermore, the addition of free radical scavengers significantly prevented lysine-induced lipid oxidative damage, suggesting that free radicals were involved in this effect. Lysine also significantly diminished glutathione levels in cortical supernatants, decreasing, therefore, the major brain antioxidant defense. Finally, lysine markedly oxidized a glutathione commercial solution in a medium devoid of brain supernatants, indicating that it behaved as a direct acting oxidant. The present data indicate that lysine induces oxidative stress in cerebral cortex of young rats. Therefore, it is presumed that this pathomechanism may be involved at least in part in the neurological damage found in patients affected by disorders with hyperlysinemia.

show abstract

“…-ATPase activity 2 h after Lys injection. Figure 6 shows that pre-treatment with melatonin did not prevent the effects of Lys on this enzyme activity [F (2,9) = 25.08; P \ 0.01].…”

Section: Resultsmentioning

confidence: 99%

“…However, large increases of Lys have been identified in blood of asymptomatic FH individuals, suggesting that hyperlysinemia itself may not be associated with a clinical phenotype [9]. On the other hand, considering that a significant number of patients with FH have progressive neurological symptoms, it is possible that the disease may correspond to a complex multifactorial condition in which hyperlysinemia play a role in combination with other trigger factors involved in the pathophysiology of the brain damage observed in the affected patients [10].…”

Section: Introductionmentioning

confidence: 98%

Neurochemical Evidence that Lysine Inhibits Synaptic Na+,K+-ATPase Activity and Provokes Oxidative Damage in Striatum of Young Rats In vivo

et al. 2010

View full text Add to dashboard Cite

Lysine (Lys) accumulation in tissues and biological fluids is the biochemical hallmark of patients affected by familial hyperlysinemia (FH) and other inherited metabolic disorders. In the present study we investigated the effects of acute administration of Lys on relevant parameters of energy metabolism and oxidative stress in striatum of young rats. We verified that Lys in vivo intrastriatal injection did not change the citric acid cycle function and creatine kinase activity, but, in contrast, significantly inhibited synaptic Na(+),K(+)-ATPase activity in striatum prepared 2 and 12 h after injection. Moreover, Lys induced lipid peroxidation and diminished the concentrations of glutathione 2 h after injection. These effects were prevented by the antioxidant scavengers melatonin and the combination of α-tocopherol and ascorbic acid. Lys also inhibited glutathione peroxidase activity 12 h after injection. Therefore it is assumed that inhibition of synaptic Na(+),K(+)-ATPase and oxidative damage caused by brain Lys accumulation may possibly contribute to the neurological manifestations of FH and other neurometabolic conditions with high concentrations of this amino acid.

show abstract

Hyperlysinemia Without Clinical Findings

Cited by 14 publications

References 13 publications

Deletion of 2‐aminoadipic semialdehyde synthase limits metabolite accumulation in cell and mouse models for glutaric aciduria type 1

Deletion of 2‐aminoadipic semialdehyde synthase limits metabolite accumulation in cell and mouse models for glutaric aciduria type 1

Lysine induces lipid and protein damage and decreases reduced glutathione concentrations in brain of young rats

Neurochemical Evidence that Lysine Inhibits Synaptic Na+,K+-ATPase Activity and Provokes Oxidative Damage in Striatum of Young Rats In vivo

Contact Info

Product

Resources

About