Mechanism of action of thyroid hormones on erythrocyte 2,3-diphosphoglyceric acid synthesis.

Normal erythrocytes, when incubated with thyroid hormone, were found to have increased levels of 2,3-diphosphoglyceric acid. In addition, a partially purified enzyme preparation, when incubated with either a 1,3-diphosphoglyceric acid generating system or 1,3-diphosphoglyceric acid directly, showed increased levels of 2,3-diphosphoglyceric acid when exposed to thyroid hormone. The hormonal effect was biphasic and was witnessed after 5 min of incubation. Substitution on the 3 and 5 positions of the basic thyronine molecule was essential for hormonal effect. It appears that thyroid hormone acts by directly stimulating the diphosphoglycerate mutase enzyme. The hormonal effect on 2,3-DPG synthesis may offer a biochemical explanation for the shift in the oxyhemoglobin dissociation curve observed in thyroid disorders.