更新于：2024-05-01
AADAC
arylacetamide deacetylase
更新于：2024-05-01
基本信息
别名 AADAC、arylacetamide deacetylase、CES5A1 + [1] |
简介 Displays cellular triglyceride lipase activity in liver, increases the levels of intracellular fatty acids derived from the hydrolysis of newly formed triglyceride stores and plays a role in very low-density lipoprotein assembly. Displays serine esterase activity in liver. Deacetylates a variety of arylacetamide substrates, including xenobiotic compounds and procarcinogens, converting them to the primary arylamide compounds and increasing their toxicity. |
关联
100 项与 AADAC 相关的临床结果
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100 项与 AADAC 相关的转化医学
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2024-02-05Infectious diseases (London, England)
Variability in plasma rifampicin concentrations and role of SLCO1B1, ABCB1, AADAC2 and CES2 genotypes in Ethiopian patients with tuberculosis.
Article
作者: Tesemma Sileshi ; Eyasu Makonnen ; Nigus Fikrie Telele ; Victoria Barclay ; Alimuddin Zumla ; Eleni Aklillu
BACKGROUND:
Rifampicin, a key drug against tuberculosis (TB), displays wide between-patient pharmacokinetics variability and concentration-dependent antimicrobial effect. We investigated variability in plasma rifampicin concentrations and the role of SLCO1B1, ABCB1, arylacetamide deacetylase (AADAC) and carboxylesterase 2 (CES-2) genotypes in Ethiopian patients with TB.
METHODS:
We enrolled adult patients with newly diagnosed TB (n = 119) who had received 2 weeks of rifampicin-based anti-TB therapy. Venous blood samples were obtained at three time points post-dose. Genotypes for SLCO1B1 (c.388A > G, c.521T > C), ABCB1 (c.3435C > T, c.4036A > G), AADACc.841G > A and CES-2 (c.269-965A > G) were determined. Rifampicin plasma concentration was quantified using LC-MS/MS. Predictors of rifampicin Cmax and AUC0-7 h were analysed.
RESULTS:
The median rifampicin Cmax and AUC0-7 were 6.76 µg/mL (IQR 5.37-8.48) and 17.05 µg·h/mL (IQR 13.87-22.26), respectively. Only 30.3% of patients achieved the therapeutic efficacy threshold (Cmax>8 µg/mL). The allele frequency for SLCO1B1*1B (c.388A > G), SLCO1B1*5 (c.521T > C), ABCB1 c.3435C > T, ABCB1c.4036A > G, AADAC c.841G > A and CES-2 c.269-965A > G were 2.2%, 20.2%, 24.4%, 14.6%, 86.1% and 30.6%, respectively. Sex, rifampicin dose and ABCB1c.4036A > G, genotypes were significant predictors of rifampicin Cmax and AUC0-7. AADACc.841G > A genotypes were significant predictors of rifampicin Cmax. There was no significant influence of SLCO1B1 (c.388A > G, c.521T > C), ABCB1c.3435C > T and CES-2 c.269-965A > G on rifampicin plasma exposure variability.
CONCLUSIONS:
Subtherapeutic rifampicin plasma concentrations occurred in two-thirds of Ethiopian TB patients. Rifampicin exposure varied with sex, dose and genotypes. AADACc.841G/G and ABCB1c.4036A/A genotypes and male patients are at higher risk of lower rifampicin plasma exposure. The impact on TB treatment outcomes and whether high-dose rifampicin is required to improve therapeutic efficacy requires further investigation.
2023-12-27The American surgeon
No Drain, No Problem: Serum-Based Marker Prediction of Clinically Relevant Postoperative Pancreatic Fistula.
Review
作者: Jessica C Heard ; Glen H Smith ; Alex Tolman ; Jashwanth S Karumuri ; Houssam G Osman ; Rohan D Jeyarajah
BACKGROUND:
Postoperative day (POD) 1 drain amylase concentration (DAC) is considered the most accurate predictor for the development of a clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreaticoduodenectomy (PD). Recent studies have associated drain placement with negative postoperative outcomes. This study aims to evaluate multiple biochemical markers and their associations with CR-POPF development in order to identify a reliable, non-drain dependent alternative to DAC.
METHODS:
This is a review of 53 consecutive PD patients between 2021 and 2022. Albumin, C-reactive protein (CRP), C-reactive protein-to-albumin ratio (CAR), DAC, white blood cell count, and procalcitonin values were compared by CR-POPF status. The discriminatory abilities of CAR, CRP, and DAC for CR-POPF were compared using receiver operating characteristic (ROC) curves.
RESULTS:
Six of 51 included patients developed a CR-POPF. Receiver operating characteristic curve analysis produced an area under the curve of .977 for POD 1 DAC (cut-off 5131.0 IU/L, sensitivity 100%, specificity 95.5%), .858 for POD 1 CRP (cut-off 52.5 mg/L, sensitivity 100%, specificity 72.7%), and 1.000 for POD 3 CAR (cut-off 99.2, sensitivity and specificity 100%). POD 3 CAR produced a positive and negative predictive value of 100%.
CONCLUSION:
The CAR and CRP provide early and accurate identification of patients with post-PD CR-POPFs. These markers offer a method of safe CR-POPF detection, when the gold standard DAC is unavailable, ultimately allowing for early intervention and patient rescue.
2023-11-03Protein science : a publication of the Protein Society
Synthesis and degradation of the cyclic dinucleotide messenger c-di-AMP in the hyperthermophilic archaeon Pyrococcus yayanosii.
Article
作者: Zheng Jin ; Dong Song ; Wei-Wei Wang ; Lei Feng ; Zheng-Xin Li ; Hai-Feng Chen ; Xiang Xiao ; Xi-Peng Liu
Cyclic di-adenosine monophosphate (c-di-AMP) is a newly identified prokaryotic cyclic dinucleotide second messenger well elucidated in bacteria, while less studied in archaea. Here, we describe the enzymes involved in c-di-AMP metabolism in hyperthermophilic archaeon Pyrococcus yayanosii. Our results demonstrate that c-di-AMP is synthesized from two molecules of ATP by diadenylate cyclase (DAC) and degraded into pApA and then to AMP by a DHH family phosphodiesterase (PDE). DAC can be activated by a wider variety of ions, using two conserved residues, D188 and E244, to coordinate divalent metal ions, which is different from bacterial CdaA and DisA. PDE possesses a broad substrate spectrum like bacterial DHH family PDEs, but shows a stricter base selection between A and G in cyclic dinucleotides hydrolysis. PDE shows differences in substrate binding patch from bacterial counterparts. C-di-AMP was confirmed to exist in Thermococcus kodakarensis cells, and the deletion of the dac or pde gene supports that the synthesis and degradation of c-di-AMP is catalysed by DAC and PDE, respectively. Our results provide further understanding of the metabolism of c-di-AMP in archaea. This article is protected by copyright. All rights reserved.
2024-03-05
·精准药物
上市批准放射疗法
2024-02-11
抗体药物偶联物多肽偶联药物
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