Neuron-specific enolase

Does anybody know the role of neuron-specific enolase (NSE), apart from tumors? Does elevated NSE play a role in ME? Does anybody here have elevated NSE?

 

Enolase is an enzyme involved in glycolysis and gluconeogenesis.

It catalyses the formation of phosphoenolpyruvate (PEP) from 2-phospho-D-glycerate and vice versa - ie, this is a reversible reaction.

In glycolysis, PEP is then converted to pyruvate which feeds into the Kreb's cycle.

In glyconeogenesis, pyruvate is converted to oxaloacetate which in turn is converted to PEP followed by glycolysis in reverse. So enolase plays a critical role in use of glucose for energy.

There are several isoforms and NSE or enolase2 (ENO2) is only found in mature neurons and cells of neuronal origin. The enzyme plays its normal role in glucose metabolism these cells.

Because there are negligible amounts of NSE in other tissues, elevated concentrations of NSE in serum or, more commonly, CSF, are used diagnostically to assist in the differential diagnosis of a variety of neuron-destructive and neurodegenerative disorders (NSE is often elevated in diseases which result in relative rapid neuronal destruction) and for some tumours (NSE is also frequently overexpressed by neural crest-derived tumors).

 

Thank you, @alicec. I think I understand. I reminded myself of alkaline phosphatase which rises, too, if certain tissues are damaged.

So I guess that there's also the possibility of low NSE. What would that mean?

If no rapid neuronal destruction can be observed, would that mean that elevated NSE levels are falsely elevated (due to, e.g., some error in blood transport, lab test...)?

Is there some research about NSE in ME? (I darkly remember there was something with enolases...maybe I am wrong though.)

What would high NSE levels mean for the Kreb's cycle? And would low NSE levels mean there are impairments with energy (glucose) metabolism? Or would that also be the case with elevated NSE?

By the way, why does tissue/nerve damage lead to higher levels of certain enzymes?

 

I don't know much about the test.

As far as I understand it, elevation associated with tissue damage is due to breakdown of cells. Normally the enzyme is inside cells and the level in blood just reflects normal tissue turnover. Increased cellular breakdown leads to elevated amounts in blood. There doesn't appear to be a lower limit - results are reported as greater than - so no value is too low.

Elevated levels in some cancers reflect overproduction of the enzyme by neuronal-derived cell types.

I really don't know if this increased production has any consequence for glucose metabolism. There are many control points in the process so these may override the influence of this particular enzyme.

Various things seem to lead to false positives - see this article from Mayo Clinic.

 

Interesting, @alicec, thank you!

Concerning low levels of enolase, I found spontaneously this:
https://en.m.wikipedia.org/wiki/Enolase_deficiency

Sounds familiar...

In case of hemolysis, according to Mayo, the NSE value can be (falsely) elevated. Which could mean that one wouldn't see low levels at all? (Which I can't imagine.) And low levels are supposed to be rare.

I guess you cannot compare enolase with neuron specific enolase.

 

That is different from low serum levels. They are talking about very rare genetic defects which result in low activity of the enolase enzyme. Interestingly, they don't describe any known cases of defects in ENO2 (NSE).

 

Ah, thanks for the correction!

How can you measure low enzyme activity?

 

There would be some kind of enzymatic assay where an excess of substrate and all other reactants are added to a sample, along with a reagent which reacts with the product in some way which can be detected fluorometrically of spectrophotometrically.

The change in this reagent is then proportional to the enolase activity in the sample.

This would be a standard research assay but whether it is performed in path labs is something I don't know. Note the assay would not be performed on serum but rather on cell lysates.

ETA

Measurement of serum enolase would be done by some kind of immunoassay - ie quantitating the binding of a known amount of an anti-enolase antibody to determine how much enolase protein is present in a sample.

 

Thank you, @alicec!