Urea cycle regulation: I. Coupling of ornithine metabolism to mitochondrial oxidative phosphorylation.
Ornithine metabolism is coupled to oxidative phosphorylation in isolated rat liver mitochondria. The pathway involving ornithine: alpha-ketoglutarate transaminase (OKT), glutamic semialdehyde dehydrogenase (GSDH), and glutamate dehydrogenase (GDH) with cycling of alpha-ketoglutarate-glutamate at the OKT reaction appears to be involved. Ornithine may be utilized by this pathway to sustain ATP levels during mitochondrial energy-deficiency states with resultant decreased urea-cycle flux and increased ammonia production. This pathophysiologic mechanism suggests that hyperammonemia is a consequence of an energy-deficiency state. Therapy directed toward alleviating the energy-deficiency state may be more beneficial than efforts to reduce ammonia levels.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000641:Ammonia / Q000097:blood; D000818:Animals; D002952:Citric Acid Cycle; D002956:Citrulline / Q000378:metabolism; D005969:Glutamate Dehydrogenase / Q000378:metabolism; D007656:Ketoglutaric Acids / Q000378:metabolism; D008930:Mitochondria, Liver / Q000378:metabolism*; D009952:Ornithine / Q000378:metabolism*; D009953:Ornithine-Oxo-Acid Transaminase / Q000378:metabolism; D010085:Oxidative Phosphorylation; D051381:Rats; D012202:Reye Syndrome / Q000378:metabolism; D014508:Urea / Q000096:biosynthesis*
D007656:Ketoglutaric Acids; D002956:Citrulline; D000641:Ammonia; D000255:Adenosine Triphosphate; D014508:Urea; D009952:Ornithine; D005969:Glutamate Dehydrogenase; D009953:Ornithine-Oxo-Acid Transaminase