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Interference by endogenous amines in the determination of monoamine oxidase activity of human platelet samples
Abstract:
Lower monoamine oxidase (MAO) levels are reported in the blood platelets from chronic schizophrenics than in normal controls. Attempts to replicate these findings in other laboratories have been unsuccessful thus contradicting the suggestion that low MAO activity is a genetically determined biological factor in schizophrenia. We now present evidence to show that the endogenous amines present in platelets (serotonin) react non-enzymatically with the highly reactive aldehyde produced by MAO and thereby reduce the extractable radioactivity in the radiometric assays for MAO. Various biogenic amines such as serotonin, dopamine and m-tyramine were tested for their interference by adding them in nanomolar concentrations to incubation mixtures containing platelet samples or partially purified rat liver MAO and (14C-)p-tyramine or phenethylamine as substrates. The amines were added before, during and after incubation. In all three cases the apparent inhibition by each amine was the same, the percent inhibition depending on the structure of the amine.
Insights
Schizophrenia research found that platelet monoamine oxidase (MAO) levels are not lower in patients. Endogenous amines interfere with MAO assays, causing inaccurate results.
Area of Science:
- Biochemistry
- Neuroscience
- Psychiatry
Background:
- Previous studies suggested lower monoamine oxidase (MAO) levels in chronic schizophrenics' blood platelets.
- Replication attempts failed, contradicting the hypothesis of low MAO activity as a genetic factor in schizophrenia.
Purpose of the Study:
- To investigate the discrepancy in reported MAO levels in schizophrenia.
- To identify factors affecting MAO activity measurements in platelet samples.
Main Methods:
- Investigated the non-enzymatic reaction between endogenous platelet amines (e.g., serotonin) and MAO-produced aldehydes.
- Assessed interference by adding biogenic amines (serotonin, dopamine, m-tyramine) to MAO assays with platelet or rat liver MAO.
- Used radiolabeled substrates (e.g., (14C-)p-tyramine) and varied amine addition timing (pre-, during, post-incubation).
Main Results:
- Endogenous amines, particularly serotonin, react non-enzymatically with MAO-generated aldehydes.
- This reaction reduces extractable radioactivity, leading to falsely low apparent MAO activity.
- Observed consistent apparent inhibition regardless of amine addition timing, dependent on amine structure.
Conclusions:
- The previously reported lower MAO levels in schizophrenia platelets are likely an artifact.
- Non-enzymatic reactions interfere with radiometric MAO assays, impacting findings in psychiatric research.
- Re-evaluation of MAO activity measurements in schizophrenia is necessary, considering amine interference.