Aminoacylase 1 (ACY1) is a cytosolic, homodimeric zinc-binding metalloenzyme with a wide range of tissue expression. It hydrolyses acylated L-amino acids (except L-aspartate) into L-amino acids and an acyl group. It can also hydrolyse N-acetylcysteine-S-conjugates. Defects in ACY1 can cause aminoacylase-1 deficiency (ACY1D; MIM:609924) resulting in encephalopathy, delay in psychomotor development, seizures and increased urinary excretion of several N-acetylated amino acids (Sass et al. 2006, Sass et al. 2007).
Cytosolic aminocyclases 1 and 3 (ACY1,3) can hydrolyse N-acylated amino acids and N-acylcysteine-S-conjugates (Lindner et al. 2003). They are functional as dimers and utilise zinc as a cofactor. Defects in ACY1 can cause aminoacylase 1 deficiency (ACY1D; MIM:609924), leading to acute encephalopathy, seizures, impaired psychomotor development and increased urinary excretion of several N-acetylated amino acids. The missense mutation R353C is associated with recessive loss-of-function phenotype and is the most common cause of enzyme deficiency (Sass et al. 2006, Sass et al. 2007).
The effects of paracetamol (APAP) poisoning can be reversed by administration of N-acetyl-L-cysteine (NAC) within 15hrs of APAP intake. This treatment is effective in preventing liver damage, hepatic failure, renal damage, and death (Prescott et al. 1977, Prescott 1981). NAC provides L-cysteine (L-Cys) for the formation of the tripeptide glutathione, which can conjugate the reactive APAP metabolite N-acetyl-p-benzoquinine imine (NAPQI), thereby reducing damage. NAC is thought to be deacetylated to L-Cys by aminocylase 1 (ACY1), a dimeric enzyme highly expressed in the kidneys (Stocker et al. 2012, review Pedre et al. 2021).
Cytosolic aminocyclases 1 and 3 (ACY1,3) can hydrolyse N-acylated amino acids and N-acylcysteine-S-conjugates (Lindner et al. 2003). They are functional as dimers and utilise zinc as a cofactor.