NADPH-dependent reductases in dog thyroid: Comparison of a third enzyme “glyceral hyde reductase” to dog thyroid aldehyde reductase

Abstract

The increased incidence of thyroiditis reported to occur in diabetes has also been observed in long-term galactose-fed dogs where it is reduced by the administration of aldose reductase inhibitors. Since this suggests that thyroidal changes are limned to the abnormal accuuulation of sugar aleobols (polyols), present studies were conducted to confirm the presence of aldose and aldehyde reductases in dog thyroid through isolation and characterization. Aldose and aldehyde reductases were isolated from dog thyroid by a series of chromatographic steps which included gel filtration on Sephadex G100, af alty chromatography on Matrex Gel Orange A and chromatofocusiog on Mono P. A third, labile NADPH-reductase was partially purified by gel filtration on Sephadex G100, affinity chromatography on Matrex Green A and bydroxylapatite chromatography on 1310-GEL HT. The kinetic properties of aldose and aldehyde reductases and their susceptibility to inhibition by allose reductase inhibitors are similar to those of dog kidney aldose and aldehyde reductases. However, the levels of aldose reductase present in thyroid are extremely low compared to the levels of aldehyde reductase. A third NADPH-depaldent reductase, tentatively identified as glyceraldebyde reductase, is also present in dog thyroid. This novel enzyme utilizes NADPH to reduce DL-glyceraldebyde and is clearly distinct from the other aldo-koto reductases in molecular weight, substrate amity, inhibition by aldose reductase inhibitors and immumological properties. In summary aldose reductase, aldehyde reductase and a third novel glyceraldebyde reductase, all of which can utilize glyceraldebyde as substrate, have been identified and characterized in dog thyroid. Only aldose and aldéhyde reductases, which can catalyze the production of polyols and were inhibited by aldose reductase inhibitors, appear to be linked to thyroiditis.