ASA is a rare genetic urea cycle disorder characterised by deficiency or lack of the enzyme argininosuccinate lyase
(ASL), which is central to two metabolic pathways: the liver-based urea cycle, which detoxifies ammonia and the citrulline-nitric oxide cycle, which synthesises nitric oxide from L-arginine.
Molecular analysis of human argininosuccinate lyase
: mutant characterization and alternative splicing of the coding region.
Fumarate accumulation in cancer cells may also reverse the activity of the urea cycle enzyme argininosuccinate lyase, leading to the production of argininosuccinate from fumarate and arginine.
The effect of increased fumarate and reversal of argininosuccinate lyase reaction, therefore, potentially allows aspartate to be diverted from the urea cycle to purine and pyrimidine biosynthesis, favoring tumor growth.
M2 EQUITYBITES-September 21, 2017-PhaseRx wins US FDA's orphan drug designation for PRX-ASL for argininosuccinate lyase deficiency
Biopharmaceutical company PhaseRx Inc (NASDAQ:PZRX) reported on Wednesday the receipt of orphan drug designation from the US Food and Drug Administration (FDA) for second drug development candidate PRX-ASL for the treatment of argininosuccinate lyase deficiency (ASLD).
M2 PHARMA-September 21, 2017-FDA Grants Orphan Drug Designation to PhaseRx for PRX-ASL for Treatment of Argininosuccinate Lyase
In addition, similar elevation of transferrin (TF), peroxiredoxin 1 (PRDX1) and 3 (PRDX3), and progesterone receptor membrane component 1 (PGRMC1) and downregulation of urea cycle enzymes such as arginase 1 (ARG1), carbamoyl-phosphate synthase 1 (CPS1), argininosuccinate lyase
(ASL), ornithine carbamoyltransferase (OTC), and argininosuccinate synthase 1 (ASS1) in the surrounding liver tissue of both the [Ogg1.sup.-/-] and [Ogg1.sup.+/+] PB groups were found.
Increased citrulline indicates a deficiency in either argininosuccinate synthase or argininosuccinate lyase
(1).Anincreased plasma argininosuccinate concentration could differentiate these deficiencies, but that did not appear in the amino acid profile.
Similarly, citrin deficiency often presents with an increased citrulline concentration, but it must be distinguished from disease caused by mutations in ASST (argininosuccinate synthetase) and ASL (argininosuccinate lyase
Argininosuccinic aciduria (ASAuria; OMIM 207900) is an autosomal recessive inborn error of the urea cycle caused by deficiency of the enzyme argininosuccinate lyase
(ASL; EC 188.8.131.52) (1).