Diabetes-associated nitration of tyrosine and inactivation of succinyl-CoA:3-oxoacid CoA-transferase.
High levels of reactive species of nitrogen and oxygen in diabetes may cause modifications of proteins. Recently, an increase in protein tyrosine nitration was found in several diabetic tissues. To understand whether protein tyrosine nitration is the cause or the result of the associated diabetic complications, it is essential to identify specific proteins vulnerable to nitration with in vivo models of diabetes. In the present study, we have demonstrated that succinyl-CoA:3-oxoacid CoA-transferase (SCOT; EC 2.8.3.5) is susceptible to tyrosine nitration in hearts from streptozotocin-treated rats. After 4 and 8 wk of streptozotocin administration and diabetes progression, SCOT from rat hearts had a 24% and 39% decrease in catalytic activity, respectively. The decrease in SCOT catalytic activity is accompanied by an accumulation of nitrotyrosine in SCOT protein. SCOT is a mitochondrial matrix protein responsible for ketone body utilization. Ketone bodies provide an alternative source of energy during periods of glucose deficiency. Because diabetes results in profound derangements in myocardial substrate utilization, we suggest that SCOT tyrosine nitration is a contributing factor to this impairment in the diabetic heart.
Turko
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IV
Department of Integrative Biology and Pharmacology, University of Texas Houston Medical School, Houston, Texas 77030, USA.
Marcondes
S
S
Murad
F
F
D000818:Animals; D002384:Catalysis; D015256:Coenzyme A-Transferases / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004734:Energy Metabolism / Q000502:physiology*; D004789:Enzyme Activation / Q000502:physiology; D007668:Kidney / Q000378:metabolism; D015227:Lipid Peroxidation / Q000502:physiology; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D026361:Reactive Nitrogen Species / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism*
D026361:Reactive Nitrogen Species; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D015256:Coenzyme A-Transferases; C021460:3-ketoacid CoA-transferase