Monoamine Oxidases MAOs EC 1434

The Parkinson's-Reversing Breakthrough

Medication for Parkinson Disease

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Cellular location: Outer membrane of mitochondria. Organ distribution: Expressed in most tissues. Prosthetic group: FAD Overall reaction:

The aldehyde formed is usually oxidized further to an acid or reduced to an alcohol by other enzymes (see Table 2.11).

Isoforms: MAO-A and MAO-B possess 70% sequence identity.

Substrates: Biogenic amines; 5-Hydroxytryptamine (5-HT) (also known as serotonin) and norepinephrine (catechol-containing) are substrates of MAO-A, and 2-phenylethylamine and benzyl amine (noncatechol-containing) are substrates of MAO-B.

Inhibitors: MAO-A is inhibited by clorgyline, and MAO-B is inhibited by (R)-deprenyl (selegiline). Pargyline inhibits both (Fig. 2.4).

Inhibitors

Substrates

Clorgyline

Clorgyline

Pargyline

5-Hydroxytryptamine (5-HT)

Phenethylamine

D-Deprenyl

Figure 2.4. Substrates and inhibitors of MAO-A and MAO-B. MAO monoamine oxidase.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was inadvertently synthesized instead of the intended MPPP (a synthetic opioid) by rogue chemists. MPTP turns out to be a neuro-toxin that causes permanent brain damage and Parkinsonism. The mechanism of toxicity is conversion to MPP+ by MAO-B in glial cells in the brain. This metabolite kills dopamine-producing neurons in the substania nigra and, hence, induces the effects of Parkinson's disease.

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