Hepatic mitochondrial energy production in rats with chronic iron overload.
BACKGROUND
Iron overload results in impaired hepatic mitochondrial oxidative metabolism. The current experiments evaluated the effects of iron overload on enzyme activities in the mitochondrial electron transport chain, on hepatic adenine nucleotide levels, and on hepatocellular oxygen consumption.


METHODS
Hepatic iron overload was produced in rats using dietary carbonyl iron. Hepatic adenine nucleotides were assessed after freeze-clamping, mitochondrial enzyme activities and oxygen consumption were measured in isolated mitochondria, and oxygen consumption in isolated hepatocytes was determined.


RESULTS
At a mean hepatic iron concentration of 4630 micrograms/g, there were no changes in reduced nicotinamide adenine dinucleotide (NADH)-cytochrome c reductase activity (complex I-III), but there was a 35% reduction in succinate-cytochrome c reductase activity (complex II-III), and a 70% decrease in cytochrome c oxidase activity (complex IV). With mild iron loading (2060 micrograms/g), there was a 28% decrease in hepatic adenosine 5'-triphosphate (ATP) levels with no change in adenosine 5'-diphosphate (ADP) or adenosine 5'-monophosphate (AMP) levels, whereas, at a higher hepatic iron concentration (3170 micrograms/g), there was a 40% reduction in ATP levels, a 22% decrease in ADP levels, with no change in AMP levels. There was a 48% reduction in oxygen consumption in isolated iron-loaded hepatocytes.


CONCLUSIONS
Chronic iron overload decreases hepatic mitochondrial cytochrome c oxidase activity, hepatocellular oxygen consumption, and hepatic ATP levels.
Bacon
B R
BR
Department of Internal Medicine, St. Louis University Health Sciences Center, Missouri.
O'Neill
R
R
Britton
R S
RS
D000244:Adenosine Diphosphate / Q000032:analysis / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000032:analysis / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000032:analysis / Q000378:metabolism; D000818:Animals; D001835:Body Weight; D002118:Calcium / Q000032:analysis; D004032:Diet; D004305:Dose-Response Relationship, Drug; D003576:Electron Transport Complex IV / Q000032:analysis; D004734:Energy Metabolism / Q000502:physiology*; D007501:Iron / Q000008:administration & dosage / Q000494:pharmacology*; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008930:Mitochondria, Liver / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000249:Adenosine Monophosphate; D008315:Malondialdehyde; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D007501:Iron; D003576:Electron Transport Complex IV; D002118:Calcium