Enolase

Related Reading

Enolase is a key glycolytic enzyme and belongs to a new type of surface protein. It does not have a classic surface transport mechanism, but is transported on the cell surface through an unknown mechanism. Enolase is a multifunctional protein whose ability to act as a plasminogen receptor on the surface of various hematopoietic, epithelial and endothelial cells suggests that it may play an important role in the fibrinolytic system in and around blood vessels. Only recently has it been recognized its role in systemic and aggressive autoimmune diseases. In addition to this feature, it also has the function of heat shock protein and the ability to bind the cytoskeleton and chromatin structure, indicating that enolase may play a vital role in transcription and various pathophysiological processes.

Figure 1. Structure of Enolase

Introductions

Glycolytic enzymes (including α-enolase) are considered "dull" enzymes because they have been conserved for millions of years. They are labeled as enzymes that do not have complex regulatory properties, and as the steady-state concentration fluctuates in response to other regulatory pressures, they only flip the substrate in either direction. Despite this boring attitude, these enzymes may be the most well-characterized proteins, and their detailed structural analysis provides a solid foundation for understanding certain basic aspects of biochemistry (especially the evolution of glycolysis and the life process itself). The latest findings indicate that these enzymes have a variety of functions in addition to innate glycolysis functions, and have important roles in several biological and pathophysiological processes. In turn, this requires us to treat them as old proteins with new faces.

Figure 2. Enolase, N-terminal domain.

Characteristics and distribution

Enolase is one of the most abundant cytoplasmic proteins expressed in many organisms. Recently, it was also found on the surface of cells. In vertebrates, the enzyme exists in the form of three isoenzymes: α-enolase exists in many tissues including the liver, while b-enolase exists almost exclusively in muscle tissue, while genolase is existed in neurons and neuroendocrine tissues. All enolase enzymes are composed of two identical subunits with a molecular weight between 82,000-100,000 Da. In mammals and humans, there are three independent genetic loci a, b and g, which encode three isoenzymes. Several earlier studies have determined from their chromatographic and immunological studies that neuron/brain-specific enolase can exist in the form of heterodimers, such as aa, ab, bb, ag, and gg. So far, no bg heterodimer isoenzyme has been found, although it has been experimentally isolated from its single homodimer counterpart.

Metal ion and enolase activity

The metal ion requirements of enzymes were first observed by Warburg and Christian and Utter and Werkman, respectively. However, only the former group first purified and crystallized enolase from yeast and performed kinetic studies. Since then, several groups have studied the importance and mechanism of enolase metal ion activation. Using equilibrium dialysis and electron spin resonance measurement techniques, a total of six divalent metal ions (magnesium, manganese, zinc, cadmium, cobalt and nickel) were determined. It was found to activate enolase. Among them, although magnesium is a naturally occurring metal activator, the binding of enolase to magnesium is much weaker than that of zinc.

Clinical signififance

In recent medical experiments, the concentration of enolase was sampled to try to diagnose certain diseases and their severity. For example, compared with other test enzymes (aldolase, pyruvate kinase, creatine kinase, and lactate dehydrogenase), a higher concentration of enolase in the cerebrospinal fluid is more associated with low-grade astrocytoma. The same study showed that patients with the highest cerebrospinal fluid enolase levels developed tumors the fastest. In recent patients with myocardial infarction or cerebrovascular accident, enolase levels have also been increased. It is inferred that the levels of CSF neuron-specific enolase, serum NSE and creatine kinase (type BB) are indicative in the prognostic evaluation of patients with cardiac arrest. Other studies have focused on the prognostic value of NSE for victims of cerebrovascular accidents.