Arginase deficiency

Iyer R et al The human arginases and arginase deficiency. J Inherit Metab Dis 1998 21 86. 

Arginase deficiency, which is inherited in an autosomai recessive manner and causes a rare hyper-argininemia. 

Arginase deficiency Arginase ARG Rarely elevated Normal... 

Supplement Essential amino acids, arginine in ASS and ASL deficiency, and citrulline in OTC and CPS deficiency Toxic Ammonia in aU UCD Argininosuccinic acid in ASL deficiency Arginine in arginase deficiency... 

Symptoms for the first four deficiencies include anorexia, vomiting and lethargy, from which patients may progress to irreversible coma (acute hepatic coma) and death. If infants survive, but remain undiagnosed and untreated for some time, they become mentally handicapped. In arginase... 

A number of inherited disorders of urea cycle metabolism are known. Hy per-ammonemia I and II are associated with CPS I and ornithine transcarbamylase deficiencies, respectively. Citrullinemia, arginosuccinic aciduria, and argininemia are associated with low levels of arginosuccinic acid synthetase, arginosuccinase, and arginase, respectively. All such disorders are associated with mental retardation, convulsions, and failure to thrive if not treated. Treatment involves the feeding of low-protein diets or, experimentally, the administration of a-keto analogs of essential amino acids instead of protein. 

The clinical syndrome of acute neonatal hyper-ammonemic encephalopathy described in the case report represents the classical presentation of a patient with a urea cycle disorder (UCD). It is important to note that this neonatal course represents only the most common and severe presentation of a UCD. This holds true for all the diseases listed in Table 18-1, with the exceptions of arginase (ARG-1) deficiency, which results in progressive spasticity of the lower limbs, and of the mitochondrial membrane transporters citrin and ornithine transporter 1 (ORNT-1). Deficiency of citrin results in adult-onset encephalopathy deficiency of... 

The final step of the urea cycle is the cleavage of arginine to release urea and regenerate ornithine. Ornithine then reenters the mitochondria via the ORNT-1 ornithine-citrulline antiporter. ARG-1 is a cytosolic homotrimeric enzyme of 35-kd monomers that is expressed in fiver and red blood cells. A second mitochondrial arginase (ARG-2) most likely plays a role in nitric oxide synthesis and is most abundant in brain, kidney, and prostate. ARG-1 deficiency is unique among the urea cycle deficiencies as patients do not present with hyperammonemia and encephalopathy but rather develop progressive spasticity of the lower limbs. Biochem-... 

Brock, A-, Chapman, S., Ulman, E and Wu, C. (1994). Dietary manganese deficiency decreases rat hepatic arginase activity /. Nirfr 124, 340-344. 

Lombeck I, Wendel U, Versieck J, van Ballenberghe L, Bremer HJ, Duran R, Wadman S. Increased manganese content and reduced arginase activity in erythrocytes of a patient with prolidase deficiency (iminodipeptiduria), Eur J Pediatr 1986 144 571-3. 

A number of inherited diseases are associated with the urea cycle. The mutations result in changes in either Vm or Km as defective proteins are produced. These include disruptions of N- acety 1 gl utam ate synthase, carbamoyl phosphate synthetase, ornithine transcarbamoylase (the most prevalent of the urea cycle deficiencies), argininosuccinate synthetase, argininosuccinate lyase, and arginase. In these diseases, when applicable, treatments are low-protein diets, to put less strain on urea cycle flux and, when appropriate, addition of amino acids as required, such as ornithine and/or arginine. 

Robbins, K.R. Baker, D.H. (1981). Kidney arginase activity in chicks fed diets containing deficient or excessive concentrations of lysine, arginine, histidine or total nitrogen. Poult. Sci., 60, 829-34. 

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