Elastase is an enzyme that digests and degrades a number of proteins including elastin, an elastic substance in the lungs and some other organs that supports their structural framework. Elastase is specifically inhibited by alpha-1 antitrypsin.
An overview of enolase
Enolase is a kind of intracellular enzyme that catalyzes the dehydration of 2-phospho-D-glycerate to phosphoenolpyruvate, a process that converts glucose into pyruvate, producing high-energy compounds such as ATP and NADH. In the anabolic direction during gluconeogenesis, they catalyze the reverse reaction of hydration of phosphoenolpyruvate to 2-phospho-D-glycerate. The glycolytic pathway and related enzymes are one of the most conserved and important metabolic networks in living organisms. As a result, enolase is among the most ubiquitously and widely expressed proteins in many species.
Major types of enolase
There are three isozymes of enolase: alpha-enolase (ENO1), beta-enolase (ENO3), gamma-enolase (NSE). Alpha-enolase is localized in all foetal and in the majority of adult mammal tissues. Beta-enolase is muscle-specific, and gamma-enolase is neuron-specific. NSE is a marker for neurons and peripheral neuroendocrine cells that exist as either γγ or αγ dimeric isozymes. While the γγ form of NSE is mainly expressed in neurons, the αγ form is expressed in microglia, oligodendrocytes, and astrocytes. In mammals, the three isoenzymes are encoded by independent loci. All enolase isoforms have a molecular range between 82 and 100 kDa and share high homology and kinetic properties.
Inhibition of enolase
Several α-enolase inhibitors with various potencies designed on the basis of substrate or intermediate analogs have been reported so far, such as the D-tartronate semialdehyde phosphate (TSP) with a Ki value in the micromolar range, 3-aminoenolpyruvate phosphate (AEP) with a Ki value in the submicromolar range, and the most potent one, phosphonoacetohydroxamate (PhAH), with a Ki value in the picomolar range. Very recently, an antibiotic, SF-2312 was identified through a similarity search to the structure of PhAH as a potent α-enolase inhibitor.
Enolase and diseases
ENO1 is a multifunctional glycolytic enzyme that is involved in cellular stress, bacterial and fungal infections, autoantigen activities, the occurrence and metastasis of cancer, parasitic infections, and the growth, development and reproduction of organisms. NSE has been implicated in ischemia, hypoxia, and diverse metabolic, proliferative, inflammatory, autoimmune, and neurodegenerative diseases.
Fig 1. Enolase in neuroprotection and neurodegeneration. (Azizul Haque et al.2018)
Tjasa Vizin, Janko Kos. Gamma-enolase: a well-known tumour marker, with a less-known role in cancer. Radiology and Oncology, 2015, 49(3):217-226.
Hong Ji, Jianfa Wang, Jingru Guo, Yue Li, Shuai Lian, Wenjin Guo, Huanmin Yang, Fanzhi Kong, Li Zhen, Li Guo, Yanzhi Liu. Progress in the biological function of alpha-enolase. Animal Nutrition, 2016, 2(1):12-17.
Azizul Haque, Rachel Polcyn, Denise Matzelle, Naren L. Banik. New Insights into the Role of Neuron-Specific Enolase in Neuro-Inflammation, Neurodegeneration, and Neuroprotection. Brain Sciences, 2018, 8(2):33.
Jrhau lung, Kuan-liang chen, chien-hui hung, chih-cheng chen, Ming-szu hung, Yu-ching lin, ching-Yuan Wu, Kuan-Der lee, neng-Yao shih, Ying huang Tsai. In silico-based identification of human α-enolase inhibitors to block cancer cell growth metabolically. Drug Design, Development and Therapy, 2017, 11: 3281-3290.