AADAC (Arylacetamide Deacetylase)

Using Aadac knockout (KO) mice, we demonstrated that CCl4, APAP, and amodiaquine induced more severe liver damage in the absence of Aadac, with elevated ferrous (Fe2+) levels, lipid peroxidation, and oxidative stress...Furthermore, human AADAC overexpression in Huh-7 cells similarly reduced intracellular Fe2+ levels and conferred protection against CCl4-induced cytotoxicity in a ceruloplasmin-dependent manner. These findings reveal a novel, non-catalytic role for AADAC in iron homeostasis and ferroptosis suppression, suggesting its clinical significance in DILI susceptibility and therapy.

Within the nervous system, AADAC may influence neurotransmitter regulation and drug metabolism. Currently, research on AADAC agonists is limited, and the development of inhibitors presents challenges, underscoring the necessity for further investigation in this area.

The increase in plasma alanine aminotransferase levels in Aadac KO mice was substantially suppressed by pretreatment with the ferroptosis inhibitors deferoxamine or ferrostatin-1, suggesting that Aadac deficiency increases susceptibility to ferroptosis...The hepatoprotective role of Aadac in ferroptosis was also observed in mice with acetaminophen-induced liver injury. This study demonstrates a novel function of AADAC in protecting against ferroptosis induced by hepatotoxicants, carbon tetrachloride and acetaminophen.

In contrast, miR-222-3p inhibition decreased lipid accumulation, which was reversed by AADAC knockdown. In conclusion, we found that hepatic AADAC was downregulated by miR-222-3p, resulting in decreased drug hydrolysis and increased lipid accumulation.

These enzymes often catalyze the conversion of prodrugs, including the COVID-19 drugs remdesivir and molnupiravir, to their pharmacologically active forms. Thus, CES and AADAC not only determine drug efficacy and toxicity but are also involved in pathophysiology. This review summarizes recent findings on the roles of CES and AADAC in drug metabolism, physiology, and pathology.

hsa_circ_0043,603 acts as a sponge for miR-1178-3p, leading to the regulation of AADAC expression and inhibition of ESCC development. These results suggest the potential of hsa_circ_0043,603 as a therapeutic and diagnostic target for ESCC.

Meanwhile, ADRA2A and AADAC could contribute to EAC pathogenesis and progression. MYO1A, ACE2, COL1A1, LGALS4, ADRA2A, AADAC, RAB27A, and P2RY14 could be potential novel diagnostic and prognostic biomarkers in BE-EAC.

AADAC protects metastatic CRC cells from ferroptosis by inhibiting lipid peroxidation in an SLC7A11-dependent manner, thus effectively promoting their metastatic colonization and growth in the liver. Together, our findings suggest that AADAC can act as a prognostic indicator and potential therapeutic target for CRLM.

AADAC can be used as a biomarker to predict the prognosis of Borrmann type III AGC and has the potential to become a new therapeutic target for GC.

Human arylacetamide deacetylase (AADAC) hydrolyzes various drugs containing an acetyl group, such as ketoconazole and rifampicin...In human hepatoma Huh-7 cells, AADAC mRNA and protein levels were significantly increased by treatment with fenofibric acid and WY-14643, PPARα ligands...These results suggested that AADAC has a role in suppressing cellular lipid accumulation. In conclusion, this study demonstrated the regulation of human AADAC by PPAR α and its significance in lipid accumulation.

The three studied parameters showed high significant sensitivity and specificity in the prediction of the presence of GC. PLEKHS1, AADAC, and CDKN3 gene expressions were suggested to be used as diagnostic and predictive biomarkers of GC, additionally, AADAC may be used as a prognostic marker in these patients for further future confirming studies.

The study demonstrated that AADAC could somehow suppress the malignant progression of ovarian cancer, especially at the cellular level. In addition, synergic tumor-inhibitory effects between AADAC and the anti-cancer drugs were identified. All the above results proposed a novel idea and candidate biomarker for ovarian cancer therapy.