[Brain monoamine oxidase in schizophrenia]

Area of Science:

• Biochemistry
• Neuroscience
• Enzymology

Background:

• Monoamine oxidase (MAO) is crucial for neurotransmitter metabolism.
• MAO dysfunction has been implicated in neurological disorders, including schizophrenia.
• Understanding MAO's structure and function is key to investigating its role in disease.

Purpose of the Study:

• To investigate the content of sulfhydryl (SH)-groups and substrate specificity of purified monoamine oxidase (MAO) from human brain.
• To compare MAO properties between individuals with schizophrenia and mentally normal individuals.
• To explore potential structural alterations in MAO associated with schizophrenia.

Main Methods:

• Purification of monoamine oxidase (MAO) from human brain tissue.
• Quantification of SH-groups per unit of protein.
• Assay of enzyme activity using MAO substrates (serotonin, beta-phenylethylamine) and a diamine oxidase substrate (histamine).
• Experimental reduction of partially oxidized SH-groups in MAO preparations.

Main Results:

• MAO from both schizophrenic and normal human brains exists in a partially oxidized state, containing approximately 2 SH-groups per 10(5) daltons.
• MAO deaminates its typical substrates (serotonin, beta-phenylethylamine) and also histamine.
• Reducing partially oxidized SH-groups in schizophrenic MAO to normal levels (15 SH-groups per 10(5) daltons) potentiated histamine deaminase activity, unlike in normal MAO where it is eliminated.
• This potentiation suggests a structural alteration in MAO in schizophrenia.

Conclusions:

• Human brain MAO is partially oxidized in both schizophrenic and normal individuals.
• MAO in schizophrenia exhibits altered substrate specificity, particularly concerning histamine deamination.
• The findings suggest a specific structural modification of MAO in schizophrenia that affects its enzymatic activity and substrate interaction.