Disease relevance of Hyperargininemia

• Argininemia is caused by a hereditary deficiency of liver-type arginase (E.C.3.5.3.1) and is characterized by psychomotor retardation and spastic tetraplegia [1].
• Deficiency of liver arginase (AI) causes hyperargininemia (OMIM 207800), a disorder characterized by progressive mental impairment, growth retardation, and spasticity and punctuated by sometimes fatal episodes of hyperammonemia [2].
• The pathobiochemistry of uremia and hyperargininemia further demonstrates a metabolic relationship between urea and guanidinosuccinic acid [3].

High impact information on Hyperargininemia

• Argininemia results from a deficiency of arginase (EC 3.5.3.1), the last enzyme of the urea cycle in the liver [4].
• To facilitate investigation of the enzyme and gene structures and to elucidate the nature of the mutation in argininemia, we isolated cDNA clones for human liver arginase [5].
• These results suggest that L-Cit formed by nNOS in L-Arg-loaded neuronal cells inhibits NOS activity and nNOS in these L-Arg-loaded cells functions as a NADPH oxidase to produce ROS, which may cause neurotoxicity in argininemia [6].
• Genomic DNAs from 11 patients with argininemia were examined using the polymerase chain reaction, cloning, and sequencing [7].
• However, whereas the argininemia can be normalized, the catabolites of arginine are still increased [8].

Chemical compound and disease context of Hyperargininemia

• Treatment of hyperargininemia with sodium benzoate and arginine-restricted diet [9].
• Lysine supplementation in hyperargininemia [10].
• Hyperargininemia: effect of ornithine and lysine supplementation [11].
• Tissue accumulation of arginine (Arg), N-acetylarginine (NA), argininic acid (AA) and homoarginine (HA) occurs in hyperargininemia, an inborn error of the urea cycle [12].
• Excretion of alpha-keto-delta-guanidinovaleric acid and its cyclic form in patients with hyperargininemia [13].

Biological context of Hyperargininemia

• In the present study we investigated the in vitro effects of arginine, N-acetylarginine, argininic acid and homoarginine on some oxidative stress parameters in rat brain in the hope to identify a possible mechanism for the brain damage in hyperargininemia [14].

Anatomical context of Hyperargininemia

• The human liver arginase gene, whose deficiency is responsible for argininemia (McKusick no. 20780), has been assigned to 6q23 through a combination of somatic cell hybrid analysis and in situ hybridization using a 1,550-base pair (bp) human DNA probe for this gene [15].
• In contrast, hyperargininemia found in patients with arginase 1 deficiency is associated with pyramidal tract findings and spasticity, without significant hyperammonemia [16].
• Controversial results have been published as to the presence of arginase activity in human skin fibroblasts in normal cells and in argininemia [17].

Gene context of Hyperargininemia

• Hyperargininemia due to liver arginase deficiency [18].
• In humans, inherited deficiency of hepatic or type I arginase results in hyperargininemia, a syndrome characterized by periodic episodes of hyperammonemia, spasticity, and neurological deterioration [19].
• Functional consequences of the G235R mutation in liver arginase leading to hyperargininemia [20].
• The results showed that all GC tested, except Arg, significantly inhibited Na+,K(+)-ATPase activity at concentrations similar to those observed in plasma and CSF of patients with hyperargininemia [21].
• Orotic acid excretion in urine in increased in ornithine transcarbamylase deficiency, citrullinemia and argininemia; it is barely increased in argininosuccinic aciduria and normal in carbamylphosphate synthetase deficiency and in hyperammonemia due to organic aciduria [22].

Analytical, diagnostic and therapeutic context of Hyperargininemia

• Beef liver arginase, an enzyme potentially useful in the therapy of arginine dependent tumors or of familial hyperargininemia, was purified to homogeneity by a procedure involving a key step of hydrophobic affinity chromatography [23].

References