Activation of liver tryptophan oxygenase by hydrocortisone, hematin and tryptophan in streptozotocin-diabetic rats |
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Authors: | E M Sadler M Weiner G G Buterbaugh |
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Institution: | Department of Pharmacology and Toxicology, University of Maryland School of Pharmacy, Baltimore, Maryland 21201, USA |
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Abstract: | This study compared changes in liver tryptophan oxygenase (TPO) activity in response to hydrocortisone, hematin and tryptophan administration to non-diabetic and diabetic (streptozotocin) rats. Hydrocortisone caused similar increases in apoenzyme (inactive), holoenzyme (heme-saturated) and total (holoenzyme + apoenzyme) TPO activities in non-diabetic and diabetic rats. The ability of hematin to increase total TPO activity was significantly less in diabetic rats. The largest differences between diabetic and non-diabetic rats were found with tryptophan which increased total TPO and holoenzyme activities 300% and 650% respectively in non-diabetic rats. However, tryptophan increased both apoenzyme (unchanged in non-diabetic rats) and holoenzyme activities by 300% in diabetic rats. These results indicate that in the diabetic state, the TPO-heme conjugation process is impaired, especially substrate mediated TPO-heme saturation. |
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Keywords: | To whom reprint requests should be addressed |
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