Monoamine oxidase inhibitory modulators in rat heart cytosol: evidence for induction by thyroid hormone.

Inhibitory modulators of monoamine oxidase (MAO) were found in rat heart 105,000 X g supernatant. The modulators inhibited MAO activity present in the outer mitochondrial membrane. The inhibition was noncompetitive when using membrane-associated MAO as enzyme source. The modulators did not, however, inhibit the enzyme activity in the soluble fraction prepared from outer mitochondrial membranes. MAO inhibitory modulator concentration in rat heart cytosol was increased by the administration of T4 to rats. Three different inhibitory molecules were identified by gel filtration studies. These results suggest that thyroid hormone regulates membrane-associated MAO activity via the production of MAO inhibitory modulators, that the modulators probably bind to specific sites on the outer mitochondrial membrane, and that this binding of modulators to the membranes may result in a structural change in the mitochondrial membrane and a decrease in MAO enzyme activity.