N-alpha-Acetyl-L-arginine, also known as N-alpha-acetylarginine is an uremic toxin which is synthesized by acetylation of arginine. The accumulation of N-a-Acetyl-L-arginine in serum happens in hyperargininemic patients. It is caused by a deficit of arginase in the liver. N-acyl-alpha amino acids are compounds containing an alpha amino acid which bears an acyl group at its terminal nitrogen atom. N-Acetylarginine can also be classified as an alpha amino acid or a derivatized alpha amino acid. Many N-acetylamino acids, including N-acetylarginine are classified as uremic toxins if present in high abundance in the serum or plasma. Uremic toxins are a diverse group of endogenously produced molecules that, if not properly cleared or eliminated by the kidneys, can cause kidney damage, cardiovascular disease and neurological deficits. N-alpha-Acetyl-L-arginine serum levels (and other guanidino compounds) were elevated of all the hyperargininemic patients are higher than the normal range. Untreated hyperargininemic patients have the highest guanidino compound levels in cerebrospinal fluid. N-alpha-Acetyl-L-arginine is also increased in the urine of hyperargininemic patients. N-alpha-Acetyl-L-arginine is one of the guanidino compounds found elevated in the serum of hemodialyzed renal insufficient (uremic) pediatric patients. N-a-Acetyl-L-arginine is synthesized from arginine which is most often synthesized through the uric acid cycle or through the consumption of arginine in protein rich foods. Glutamine is consumed through food and taken into the blood through the intestines. It is transported to the liver where it is transported in via an amino acid transport. Glutamine is then transported into the mitochondria by the transporter glutamate antiporter SLC25A12, mitochondrial. In the mitochondria it is catalyzed by Glutaminase liver isoform, mitochondrial into glutamic acid. Glutamic acid is carboxylated into 1-Pyrroline-5-carboxylic acid by the enzyme Delta-1-pyrroline-5-carboxylate synthase. 1-Pyrroline-5-carboxylic acid with glutaric acid synthesize Oxoglutaric acid and ornithine with the enzyme Ornithine aminotransferase, mitochondrial. Ornithine and Carbamoyl phosphate are catalyzed by the enzyme ornithine carbamoyltransferase, mitochondrial to synthesize citrulline. Citrulline is transported out of the mitochondria into the cytosol by a mitochondrial transporter. Arginnosuccinate is synthesized from citrulline and aspartic acid by the enzyme argininosuccinate synthase. That is catalyzed by argininosuccinate lyase to produce arginine and fumaric acid. Arginine accumulates because it cannot be catalyzed into Urea and Ornithine. The accumulated arginine is acetylated into N-alpha-Acetyl-L-arginine which is transported into the blood. In the blood it works as a uremic toxin to cause kidney damage, cardiovascular disease and neurological deficits.

Metabolism and Physiological Effects of N-alpha-Acetyl-L-arginine References