更新于：2024-11-01

asparaginase

更新于：2024-11-01

基本信息

别名

1-alkyl-2-acetylglycerophosphocholine esterase、60 kDa lysophospholipase、60-kDa-lysophospholipase

+ [11]

简介

Exhibits lysophospholipase, transacylase, PAF acetylhydrolase and asparaginase activities (By similarity). Can catalyze three types of transacylation reactions: (1) acyl transfer from 1-acyl-sn-glycero-3-phosphocholine (1-acyl-GPC) to the sn-1(3) positions of glycerol and 2-acylglycerol (sn-1 to -1(3) transfer), (2) acyl transfer from 1-acyl-GPC to the sn-2 positions of 1-acyl-GPC, 1-acyl-sn-glycero-3-phosphoethanolamine (1-acyl-GPE), and other lysophospholipids (sn-1 to -2 transfer) and (3) acyl transfer from 2-acyl-GPC to the sn-1 position of 2-acyl-GPC and 2-acyl-GPE (sn-2 to -1 transfer) (By similarity). Mediates the synthesis of 1-arachidonoyl species of phospholipids by transferring the arachidonoyl residue from 2-arachidonoyl lysophospholipid to the sn-1 position of 2-acyl lysophospholipid (By similarity).

关联

项与 asparaginase 相关的药物

L-asparaginase (Claris Lifesciences Ltd.)

L-天冬酰胺酶 (Claris Lifesciences Ltd.)

靶点

asparaginase

作用机制

asparaginase刺激剂

在研机构

Claris Lifesciences Ltd.

原研机构

Claris Lifesciences Ltd.

在研适应症

急性淋巴细胞白血病

非在研适应症-

最高研发阶段批准上市

首次获批国家/地区-

首次获批日期1800-01-20

An-107

靶点

asparaginase

作用机制

asparaginase inhibitors

在研机构

Emory University [+1]

原研机构

Emory University [+1]

在研适应症

急性淋巴细胞白血病

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 asparaginase 相关的临床结果

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100 项与 asparaginase 相关的转化医学

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0 项与 asparaginase 相关的专利（医药）

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677

项与 asparaginase 相关的文献（医药）

2024-12-31·Gut Microbes

Protection against fibrosis by a bacterial consortium in metabolic dysfunction-associated steatohepatitis and the role of amino acid metabolism

Article

作者: Beretta, Laura ; Fisher-Hoch, Susan P. ; Futreal, P. Andrew ; Jenq, Robert R. ; Jamal, Mohamed A. ; Hawk, Ernest T. ; Tan, Lin ; McCormick, Joseph B. ; Kwan, Suet-Ying ; Lorenzi, Philip L. ; Gonzales, Kristyn A. ; Stevenson, Heather L.

The gut microbiota drives progression to liver fibrosis, the main determinant of mortality in metabolic dysfunction-associated steatohepatitis (MASH). In this study, we aimed to identify bacterial species associated with protection against liver fibrosis in a high-risk population, and test their potential to protect against liver fibrosis in vivo. Based on stool shotgun metagenomic sequencing of 340 subjects from a population cohort disproportionally affected by MASH, we identified bacterial species from the Bacteroidales and Clostridiales orders associated with reduced risk of liver fibrosis. A bacterial consortium was subsequently tested in a mouse model of MASH, which demonstrated protective effects against liver fibrosis. Six of the eight inoculated bacteria were detected in mouse stool and liver. Intrahepatic presence of bacteria was further confirmed by bacterial culture of mouse liver tissue. Changes in liver histological parameters, gut functional profiles, and amino acid profiles were additionally assessed. Comparison between fibrosis-associated human metagenome and bacteria-induced metagenome changes in mice identified microbial functions likely to mediate the protective effect against liver fibrosis. Amino acid profiling confirmed an increase in cysteine synthase activity, associated with reduced fibrosis. Other microbiota-induced changes in amino acids associated with reduced fibrosis included increased gut asparaginase activity and decreased hepatic tryptophan-to-kynurenine conversion. This human-to-mouse study identified bacterial species and their effects on amino acid metabolism as innovative strategies to protect against liver fibrosis in MASH.

2024-11-01·International Journal of Biological Macromolecules

Expression, characterization and cytotoxicity of recombinant l-asparaginase II from Salmonella paratyphi cloned in Escherichia coli

Article

作者: Alokail, Majed S. ; Bhat, Sheraz Ahmad ; Abdullah, Ejlal Mohamed ; Karthikeyan, Subramani ; Aziz, Ibrahim M. ; Alokail, Majed S ; Ataya, Farid Shokry ; Rupavarshini, Manoharan ; Aziz, Ibrahim M ; Khan, Mohd Shahnawaz

L-asparaginase is a remarkable antineoplastic enzyme used in medicine for the treatment of acute lymphoblastic leukemia (ALL) as well as in food industries. In this work, the L-asparaginase-II gene from Salmonella paratyphi was codon-optimized, cloned, and expressed in E. coli as a His-tag fusion protein. Then, using a two-step chromatographic procedure it was purified to homogeneity as confirmed by SDS-PAGE, which also showed its monomeric molecular weight to be 37 kDa. This recombinant L-asparaginase II from Salmonella paratyphi (recSalA) was optimally active at pH 7.0 and 40 °C temperature. It was highly specific for L-asparagine as a substrate, while its glutaminase activity was low. The specific activity was found to be 197 U/mg and the kinetics elements K_m, V_max, and k_cat were determined to be 21 mM, 28 μM/min, and 39.6 S^-1, respectively. Thermal stability was assessed using a spectrofluorometer and showed T_m value of 45 °C. The in-vitro effects of recombinant asparaginase on three different human cancerous cell lines (MCF7, A549 and Hep-2) by MTT assay showed remarkable anti-proliferative activity. Moreover, recSalA exhibited significant morphological changes in cancer cells and IC₅₀ values ranged from 28 to 45.5 μg/ml for tested cell lines. To investigate the binding mechanism of SalA, both substrates L-asparagine and l-glutamine were docked with the protein and the binding energy was calculated to be -4.2 kcal mol^-1 and - 4.4 kcal mol^-1, respectively. In summary, recSalA has significant efficacy as an anticancer agent with potential implications in oncology while its in-vivo validation needs further investigation.

2024-10-01·Ecotoxicology and Environmental Safety

The mitigating effects and mechanisms of Bacillus cereus on chronic cadmium poisoning in Litopenaeus vannamei based on histopathological, transcriptomic, and metabolomic analyses

Article

作者: Dong, Jiaxin ; Wang, Xuejie ; Qian, Zhaoying ; Gao, Shan ; Sun, Chengbo ; Hou, Danqing ; Yu, Jianbo

Shrimp are non-negligible victims of cadmium (Cd) contamination, and there is still a lack of strategies for mitigating Cd toxicity in shrimp. Bacillus cereus, with its significant heavy metal (HM) tolerance and chelating effects, is a representative beneficial bacterium to be investigated for mitigating the toxicity of Cd exposure. This study revealed the effects and potential mechanisms of B. cereus in mitigating chronic Cd toxicity in shrimp by analyzing growth performance, hepatopancreatic Cd accumulation, pathology, as well as comprehensive hepatopancreatic transcriptomics and metabolomics in Litopenaeus vannamei. The results showed that shrimp's growth inhibition, hepatopancreatic Cd accumulation and physiological structure damage in B. cereus+chronic Cd group were effectively alleviated compared with the chronic Cd treatment group. The pathways related to amino acid metabolism, glycolipid metabolism, immune response, and antioxidant stress were significantly activated in the B. cereus+chronic Cd group, including glycolysis, pentose phosphate pathway, oxidative phosphorylation, biosynthesis of amino acids, and biosynthesis of unsaturated fatty acids pathways. The key differentially expressed genes (e.g., macrophage migration inhibitory factor, glycine cleavage system H protein, glycine dehydrogenase, phosphoglucomutase-2, asparaginase, ATP synthase subunit, cytochrome c, and 4-hydroxyphenylpyruvate dioxygenase) and metabolites (e.g., L-leucine, D-ribose, gluconic acid, 6-Phosphogluconic acid, sedoheptulose 7-phosphate, 1-Kestose, glyceric acid, arachidic acid, prostaglandins, 12-Keto-tetrahydro-leukotriene B4, and gamma-glutamylcysteine) associated with the above pathways were significantly altered. This study demonstrated that B. cereus is an effective mitigator for the treatment of chronic Cd poisoning in shrimp. B. cereus may play a role in alleviating the toxicity of Cd by enhancing the antioxidant performance, immune defense ability, metabolic stability, and energy demand regulation of shrimp. The study provides reference materials for the study of B. cereus in alleviating Cd toxicity of shrimp and broadens the application of probiotics in treating HM toxicity.