Amino acids ornithine transcarbamylase

The carbamoyl group of carbamoyl phosphate is transferred to the amino acid ornithine to form citrulline under the influence of the mitochondrial enzyme ornithine transcarbamylase (ornithine carbamoyltransferase). Ornithine and citrulline are a-amino acids which do not occur in proteins (page 36), The ornithine transcarbamylase reaction is also effectively irreversible. 

While the a-amino group of ornithine could also react with acetyl -P, this possibility was eliminated in a number of ways. Chromatography in the automatic recording amino acid analyzer by the procedure of Spackman, Stein, and Moore (41) yields excellent separation of 6-acetylornithine and a-acetylornithine. Only traces of a -acetylornithine have been detected with ornithine transcarbamylase and acetyl-P the product is always better than 95% 6-acetylornithine. The separation of a- and 6-acetylornithine by paper chromatography is not practically feasible, although both acetyl derivatives are very readily separated from ornithine (15). 6-Acetylornithine is a natural product first isolated from a Siberian plant 26 years ago (28) and now known to be present in many plants (39). 

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. 

Diagnosis is based upon hyperammonaemia, which is detectable either spontaneously or after the oral intake of proteins - or, most obviously, following intravenous infusion of amino acids. The respective amino acids are increased in the serum prior to the disturbed metabolic reaction. Argininosuccinate is only detectable in the urine. A striking feature in these patients is their thin, brittle hair. With defective ornithine transcarbamylase, there is an increase in orotic acid, uridine and uric acid in the urine, while the respective citrulline concentration is decreased. The determination of OTC activity in liver tissue verifies the diagnosis and facilitates a genomic analysis. (172) The allopurinol test can be applied for the identification of heterozygosity (or the mild form of OTC deficiency). The liver shows steatosis, portal inflammation and portal fibrosis. 

Citrulline is an endogenous amino acid involved in the urea cycle. Clinically, it can be used as an arginine substitute in the treatment of inborn errors of urea synthesis, including carbamyl phosphate synthetase and ornithine transcarbamylase. It is also a diuretic. 

The metabolic team was consulted and obtained STAT biochemical labs including plasma acylcamitine profile, plasma amino acids, urine organic acids, and urine orotic acid. Labs showed elevated orotic acid as well as a plasma amino-acid pattern consistent with ornithine transcarbamylase (OTC) deficiency. The newborn screen was normal. The infant was placed on a protein-restricted diet, supplemented with arginine, and started on nitrogen-scavenging medications. 

Ornithine tianscarbeunylase (OTC) deficiency intellectual disability Ornithine transcarbamylase Hyperaimnonemia, respiratoiy alkalosis Lethargy, vomiting, apnea, coma and death if untreated intellectual disability Protein restriction essential amino acid and arginine supplementation (in conjrmction with nitrogen scavenging medications) None... 

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