Pathways

Ornithine aminotransferase deficiency (OAT deficiency, ornithine keto acid aminotransferase deficiency, OKT deficiency, ornithine-delta-aminotransferase deficiency, gyrate atrophy of the choroid and retina) is an autosomal recessive disorder of ornithine metabolism caused by a defective ornithine aminotransferase (OAT). OAT catalyzes the conversion of ornithine into proline which is a conditionally essential amino acid. This disease is characterized by a very large accumulation of ornithine in the blood. Symptoms of the disease include tunnel vision, night blindness, myopia, and progressive vision loss.

Ornithine aminotransferase deficiency (OAT deficiency, ornithine keto acid aminotransferase deficiency, OKT deficiency, ornithine-delta-aminotransferase deficiency, gyrate atrophy of the choroid and retina) is an autosomal recessive disorder of ornithine metabolism caused by a defective ornithine aminotransferase (OAT). OAT catalyzes the conversion of ornithine into proline which is a conditionally essential amino acid. This disease is characterized by a very large accumulation of ornithine in the blood. Symptoms of the disease include tunnel vision, night blindness, myopia, and progressive vision loss.

In the ornithine biosynthesis pathway of E. coli, L-glutamate is acetylated to N-acetylglutamate by the enzyme N-acetylglutamate synthase, encoded by the argA gene. The acetyl donor for this reaction is acetyl-CoA. N-acetylglutamic acid is then phosphorylated via an ATP driven acetylglutamate kinase which yields a N-acetyl-L-glutamyl 5-phosphate. The product undergoes a NADPH dependent reduction resulting in N-acetyl-L-glutamate 5-semialdehyde which then reacts with L-glutamic acid through a acetylornithine aminotransferase / N-succinyldiaminopimelate aminotransferase to produce a N-acetylornithine. Deacetylated through an acetylornithine deacetylase, N-acetylornithine finally yields an ornithine. Ornithine interacts with hydrogen ion through an ornithine decarboxylase resulting in a carbon dioxide release and a putrescine. Putrescine can be metabolized by reaction with either l-glutamic acid or oxoglutaric acid. If putrescine reacts with L-glutamic acid, it reacts through an ATP mediated gamma-glutamylputrescine producing a hydrogen ion, ADP, phosphate and gamma-glutamyl-L-putrescine. This compound is reduced by interacting with oxygen, water and a gamma-glutamylputrescine oxidoreductase resulting in ammonium, hydrogen peroxide and 4-gamma-glutamylamino butanal. The previous product is then dehydrogenated through a NADP mediated reaction lead by gamma-glutamyl-gamma-aminobutaryaldehyde dehydrogenase resulting in hydrogen ion, NADPH and 4-glutamylamino butanoate. In turn, the latter compound reacts with water through a gamma-glutamyl-gamma-aminobutyrate hydrolase resulting in L-glutamic acid and Gamma aminobutyric acid. On the other hand, if putrescine reacts with oxoglutaric acid through a putrescine aminotransferase, it results in L-glutamic acid, and a 4-aminobutyraldehyde. 4-aminobutyraldehyde reacts with water through a NAD dependent gamma aminobutyraldehyde dehydrogenase resulting in hydrogen ion, NADH and gamma-aminobutyric acid. Gamma Aaminobutyric acid reacts with oxoglutaric acid through 4-aminobutyrate aminotransferase resulting in L-glutamic acid and succinic acid semialdehyde. Succinic acid semialdehyde in turn can react with with either NADP or NAD to result in the production of succinic acid through succinate-semialdehyde dehydrogenase or aldehyde dehydrogenase-like protein yneI respectively. Succinic acid can then be integrated in the TCA cycle.

In the ornithine biosynthesis pathway of E. coli, L-glutamate is acetylated to N-acetylglutamate by the enzyme N-acetylglutamate synthase, encoded by the argA gene. The acetyl donor for this reaction is acetyl-CoA. N-acetylglutamic acid is then phosphorylated via an ATP driven acetylglutamate kinase which yields a N-acetyl-L-glutamyl 5-phosphate. The product undergoes a NADPH dependent reduction resulting in N-acetyl-L-glutamate 5-semialdehyde which then reacts with L-glutamic acid through a acetylornithine aminotransferase / N-succinyldiaminopimelate aminotransferase to produce a N-acetylornithine. Deacetylated through an acetylornithine deacetylase, N-acetylornithine finally yields an ornithine. Ornithine interacts with hydrogen ion through an ornithine decarboxylase resulting in a carbon dioxide release and a putrescine. Putrescine can be metabolized by reaction with either l-glutamic acid or oxoglutaric acid. If putrescine reacts with L-glutamic acid, it reacts through an ATP mediated gamma-glutamylputrescine producing a hydrogen ion, ADP, phosphate and gamma-glutamyl-L-putrescine. This compound is reduced by interacting with oxygen, water and a gamma-glutamylputrescine oxidoreductase resulting in ammonium, hydrogen peroxide and 4-gamma-glutamylamino butanal. The previous product is then dehydrogenated through a NADP mediated reaction lead by gamma-glutamyl-gamma-aminobutaryaldehyde dehydrogenase resulting in hydrogen ion, NADPH and 4-glutamylamino butanoate. In turn, the latter compound reacts with water through a gamma-glutamyl-gamma-aminobutyrate hydrolase resulting in L-glutamic acid and Gamma aminobutyric acid. On the other hand, if putrescine reacts with oxoglutaric acid through a putrescine aminotransferase, it results in L-glutamic acid, and a 4-aminobutyraldehyde. 4-aminobutyraldehyde reacts with water through a NAD dependent gamma aminobutyraldehyde dehydrogenase resulting in hydrogen ion, NADH and gamma-aminobutyric acid. Gamma Aaminobutyric acid reacts with oxoglutaric acid through 4-aminobutyrate aminotransferase resulting in L-glutamic acid and succinic acid semialdehyde. Succinic acid semialdehyde in turn can react with with either NADP or NAD to result in the production of succinic acid through succinate-semialdehyde dehydrogenase or aldehyde dehydrogenase-like protein yneI respectively. Succinic acid can then be integrated in the TCA cycle.

Ornithine transcarbamylase deficiency (OTC deficiency), is a rare inborn error of metabolism (IEM) and X-linked disorder of the urea cycle caused by a deficiency of ornithine transcarbamylase. Ornithine transcarbamylase is responsible for processing nitrogen produced by the urea cycle. This disorder is characterized by a large accumulation of ammonia in the bloodstream. Symptoms of the disorder include lethargy, seizures, or coma. Treatment with hemodialysis is very effective in patients with high ammonia blood levels. It is estimated that ornithine transcarbamylase deficiency affects 1 in 14,000 to 1 in 77,000 individuals. These estimates are very different because adults with the late-onset form of ornithine transcarbamylase deficiency are less likely to come to medical attention.

Ornithine transcarbamylase deficiency (OTC deficiency), is a rare inborn error of metabolism (IEM) and X-linked disorder of the urea cycle caused by a deficiency of ornithine transcarbamylase. Ornithine transcarbamylase is responsible for processing nitrogen produced by the urea cycle. This disorder is characterized by a large accumulation of ammonia in the bloodstream. Symptoms of the disorder include lethargy, seizures, or coma. Treatment with hemodialysis is very effective in patients with high ammonia blood levels. It is estimated that ornithine transcarbamylase deficiency affects 1 in 14,000 to 1 in 77,000 individuals. These estimates are very different because adults with the late-onset form of ornithine transcarbamylase deficiency are less likely to come to medical attention.

Ornithine transcarbamylase deficiency (OTC deficiency), is a rare inborn error of metabolism (IEM) and X-linked disorder of the urea cycle caused by a deficiency of ornithine transcarbamylase. Ornithine transcarbamylase is responsible for processing nitrogen produced by the urea cycle. This disorder is characterized by a large accumulation of ammonia in the bloodstream. Symptoms of the disorder include lethargy, seizures, or coma. Treatment with hemodialysis is very effective in patients with high ammonia blood levels. It is estimated that ornithine transcarbamylase deficiency affects 1 in 14,000 to 1 in 77,000 individuals. These estimates are very different because adults with the late-onset form of ornithine transcarbamylase deficiency are less likely to come to medical attention.

Ornithine transcarbamylase deficiency (OTC deficiency), is a rare inborn error of metabolism (IEM) and X-linked disorder of the urea cycle caused by a deficiency of ornithine transcarbamylase. Ornithine transcarbamylase is responsible for processing nitrogen produced by the urea cycle. This disorder is characterized by a large accumulation of ammonia in the bloodstream. Symptoms of the disorder include lethargy, seizures, or coma. Treatment with hemodialysis is very effective in patients with high ammonia blood levels. It is estimated that ornithine transcarbamylase deficiency affects 1 in 14,000 to 1 in 77,000 individuals. These estimates are very different because adults with the late-onset form of ornithine transcarbamylase deficiency are less likely to come to medical attention.