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Thyroid hormone-inducible monoamine oxidase inhibitor in rat liver cytosol
T Obata1, M Tamura, Y Yamanaka
1Department of Pharmacology, Medical College of Oita, Japan.
Abstract:
An endogenous inhibitor of monoamine oxidase (MAO) was separated by gel-filtration from 105,000 g supernate of T4-treated rat liver cytosol. The inhibition by this inhibitor was concentration-dependent and more potent for A-form MAO than for B-form MAO. The mode of inhibition was competitive either with 5-hydroxytryptamine or beta-phenylethylamine. The molecular weight of this inhibitor was estimated to be 600-700 by gel filtration. The pI value was determined to be 3.0 by isoelectric focusing. This inhibitor was proved to be heat-stable and resistant to protease treatment. MAO inhibition activity was much lower in the cytosol of thyroidectomized, non-T4-treated rats than T4-treated rats, suggesting that this inhibitor is induced by thyroid hormone T4. MAO activity in rat liver might be regulated by the level of this inhibitor.
Insights
Thyroid hormone T4 induces an endogenous inhibitor of monoamine oxidase (MAO) in rat liver. This heat-stable inhibitor preferentially blocks MAO-A activity, suggesting a regulatory role in liver MAO function.
Area of Science:
- Biochemistry
- Endocrinology
- Enzymology
Background:
- Monoamine oxidase (MAO) enzymes are crucial for neurotransmitter metabolism.
- Thyroid hormones influence various metabolic processes, but their role in regulating MAO activity is not fully understood.
- Endogenous inhibitors can play a significant role in controlling enzyme function.
Purpose of the Study:
- To identify and characterize an endogenous inhibitor of MAO in rat liver.
- To investigate the influence of thyroid hormone (T4) on the levels and activity of this inhibitor.
- To determine the kinetic properties and physicochemical characteristics of the MAO inhibitor.
Main Methods:
- Gel filtration chromatography to isolate the inhibitor from rat liver cytosol.
- Enzyme kinetic assays to determine inhibition type and potency against MAO-A and MAO-B.
- Isoelectric focusing and heat/protease stability tests to characterize the inhibitor.
- Comparison of inhibitor levels in T4-treated versus thyroidectomized rats.
Main Results:
- An endogenous MAO inhibitor was isolated from T4-treated rat liver cytosol.
- The inhibitor exhibited competitive inhibition, preferentially targeting MAO-A.
- Estimated molecular weight of 600-700 Da and a pI of 3.0.
- The inhibitor was heat-stable and protease-resistant.
- Inhibitor levels were significantly lower in rats lacking T4, indicating T4 induction.
Conclusions:
- Thyroid hormone T4 induces the production of an endogenous MAO inhibitor in rat liver.
- This inhibitor, likely regulating MAO-A activity, is heat-stable and has a low pI.
- MAO activity in rat liver may be modulated by the concentration of this T4-induced inhibitor.