For most enolases fluoride acts as an inhibitor
For most enolases, fluoride acts as an inhibitor, while Mg2+ is the most important metal activator. In yeast systems, metal cations and fluoride bind to enolase at the active center of the enzyme, forming a complex. The complex blocks the binding of substrates to the enzyme in yeast systems, thereby exerting an inhibitory effect. Studies have also found that Mg2+ is an activator of Leuconostoc mesenteroides 512FMCM. In addition, Mn2+ and Zn2+ exhibit the same effect (Lee et al., 2006). Manganous ions shows a strong activating effect on the enolases of Candida albicans and yeast. However, the activating effect of Mn2+ on carp muscle enolase is rather weak. Compared with Mn2+, Zn2+ exerts a much stronger activating effect on carp enolase but a weaker effect on yeast enolases and C. albicans enolases. The above discoveries indicate that distinct activators and inhibitors exist for different animal enolases.
Alpha-enolase is abundantly expressed in most cells. Alpha-enolase is abundant in the Milnacipran HCl and is also present at the cell surface and in nuclei (Pancholi and Fischetti, 1998). Because of the conservative nature of glycolytic enzymes (including ENO1) across millions of years, this class of enzymes is generally considered rather “dull”. Glycolytic enzymes have even been labeled “void of sophisticated regulatory functions” because only minor changes in the concentrations of the enzymes occur in the presence of external stimuli and the enzymes only play a catalytic role in certain reactions. However, unlike the glyceraldehyde 3-phosphate dehydrogenase (GAPDH) gene, ENO1 is not a housekeeping gene. The expression of ENO1 changes with the occurrence of pathological changes in organisms and over the course of cell growth. Current studies show that, in addition to their glycolytic activities, the glycolytic enzymes play important roles in several biological and pathophysiological processes. Specifically, studies demonstrate that ENO1 is closely related to cancer, systemic fungal disease, odontopathy and autoimmune diseases.
Biological functions of ENO1
Acknowledgement The work was supported by the Natural Science Foundation of China (31302052) and the Natural Science Foundation of Heilongjiang Province of China (ZD201116). The authors would like to thank the anonymous reviewers for their valuable comments and suggestions.
Introduction Caries, which is a multifactorial disease, is principally caused by Streptococcus mutans. Fluoride materials are commonly used to control the disease, since fluoride inhibits demineralization and promotes remineralization of the tooth surface by forming fluorohydroxyapatite . Fluoride also inhibits bacterial acid production in vitro and plaque acid production in vitro. S. mutans ferments various carbohydrates, which decreases the environmental pH and leads to the formation of hydrogen fluoride (HF). HF can cross the cell membrane and easily enter the bacterium because of its higher pH inside the cell than outside. It is thought that inhibition of two enzymes is responsible for the antibacterial activity of fluoride: enolase, which is involved in glycolytic metabolism, and ATPase, which is associated with ion transportation and maintenance of ionic gradients . Addition of fluoride to a cell suspension of S. mutans results in intracellular accumulation of 3- and 2-phosphoglycerate (enolase substrates) and a decrease in phosphoenolpyruvate (PEP; enolase product) in the Embden–Meyerhof–Parnas pathway, which leads to a decrease in glucose uptake. Inhibition of ATPase results in intracellular acidification with suppression of the H+ efflux. In Japan, methods for systemic fluoride application such as water fluoridation have not been applied. Fluoride is usually provided by fluoride-containing toothpaste, gels, and mouth rinses. Children often have tooth decay despite routine use of these fluoride-containing products. Although it is possible that the levels of fluoride used are not sufficient, another possibility is that fluoride-resistant S. mutans may be contributing to the occurrence of dental caries in these children. Although the occurrence of fluoride-resistant S. mutans in the population is unclear, it has been shown experimentally that fluoride-resistant S. mutans strains can be generated , . Therefore, we investigated the fluoride sensitivity of different S. mutans strains, with a focus on enolase activity.