Coenzyme Q1 redox metabolism during passage through the rat pulmonary circulation and the effect of hyperoxia.

Abstract

The objective was to evaluate the pulmonary disposition of the ubiquinone homolog coenzyme Q(1) (CoQ(1)) on passage through lungs of normoxic (exposed to room air) and hyperoxic (exposed to 85% O(2) for 48 h) rats. CoQ(1) or its hydroquinone (CoQ(1)H(2)) was infused into the arterial inflow of isolated, perfused lungs, and the venous efflux rates of CoQ(1)H(2) and CoQ(1) were measured. CoQ(1)H(2) appeared in the venous effluent when CoQ(1) was infused, and CoQ(1) appeared when CoQ(1)H(2) was infused. In normoxic lungs, CoQ(1)H(2) efflux rates when CoQ(1) was infused decreased by 58 and 33% in the presence of rotenone (mitochondrial complex I inhibitor) and dicumarol [NAD(P)H-quinone oxidoreductase 1 (NQO1) inhibitor], respectively. Inhibitor studies also revealed that lung CoQ(1)H(2) oxidation was via mitochondrial complex III. In hyperoxic lungs, CoQ(1)H(2) efflux rates when CoQ(1) was infused decreased by 23% compared with normoxic lungs. Based on inhibitor effects and a kinetic model, the effect of hyperoxia could be attributed predominantly to 47% decrease in the capacity of complex I-mediated CoQ(1) reduction, with no change in the other redox processes. Complex I activity in lung homogenates was also lower for hyperoxic than for normoxic lungs. These studies reveal that lung complexes I and III and NQO1 play a dominant role in determining the vascular concentration and redox status of CoQ(1) during passage through the pulmonary circulation, and that exposure to hyperoxia decreases the overall capacity of the lung to reduce CoQ(1) to CoQ(1)H(2) due to a depression in complex I activity.

• Authors: Said H Audi, Marilyn P Merker, Gary S Krenz, Taniya Ahuja, David L Roerig, Robert D Bongard
• Journal: Journal of applied physiology (Bethesda, Md. : 1985) (J Appl Physiol (1985)) Vol. 105 Issue 4 Pg. 1114-26 (Oct 2008) ISSN: 8750-7587 [Print] United States
• PMID: 18703762 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Enzyme Inhibitors
• Ubiquinone
• Oxidoreductases
• NAD(P)H Dehydrogenase (Quinone)
• NQO1 protein, rat
• Electron Transport Complex I
• Electron Transport Complex III
• Ubiquinone Q1

Topics

• Animals
• Disease Models, Animal
• Electron Transport Complex I (metabolism)
• Electron Transport Complex III (metabolism)
• Enzyme Inhibitors (pharmacology)
• Hyperoxia (enzymology, physiopathology)
• Kinetics
• Lung (blood supply, drug effects, enzymology)
• Mitochondria (enzymology)
• Models, Cardiovascular
• NAD(P)H Dehydrogenase (Quinone) (metabolism)
• Oxidation-Reduction
• Oxidoreductases (antagonists & inhibitors, metabolism)
• Pulmonary Circulation
• Rats
• Rats, Sprague-Dawley
• Ubiquinone (blood)