Iron deficiency anemia: mitochondrial alpha-glycerophosphate dehydrogenase in guinea pig skeletal muscle.
Severe iron deficiency anemia in rats causes a decrease in the activities of iron-containing enzymes in skeletal muscle mitochondria, and subsequent diminished respiratory activity has been linked to lowered work capacity. It was suggested that loss of mitochondrial alpha-glycerophosphate dehydrogenase activity plays a particularly important role in this process and, by inference, in the clinical manifestations of iron deficiency anemia. This view may be ill founded, inasmuch as other pathways with potentially greater activity are capable of transporting reducing equivalents from the cytosol into the mitochondria in mammalian skeletal muscle. In our experiments, iron deficiency anemia of a severity on the order of that in humans was produced in guinea pigs. Mitochondria from skeletal muscles of test animals exhibited respiration rates diminished by 24% to 36% compared with control mitochondria in the presence of several substrates. However, differences in respiration were not observed with alpha-glycerophosphate as substrate, nor were there differences in alpha-glycerophosphate dehydrogenase enzyme activity between mitochondria from iron-deficient and control animals. Although cytochrome oxidase activity and muscle mitochondrial protein content were the same in both groups of guinea pigs, cytochrome and flavoprotein concentrations were lower in mitochondria from iron-deficient animals and there was a preferential loss of cytochrome c + c1. Iron deficiency anemia in guinea pigs thus results in impaired oxygen metabolism in skeletal muscle mitochondria that is associated with a general decrease in the concentrations of iron-containing electron transport chain components as well as with an alteration in chain stoichiometry.(ABSTRACT TRUNCATED AT 250 WORDS)
Macdonald
V W
VW
Charache
S
S
Hathaway
P J
PJ
D000747:Anemia, Hypochromic / Q000201:enzymology*; D000818:Animals; D003574:Cytochrome c Group / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D005260:Female; D005420:Flavoproteins / Q000378:metabolism; D005993:Glycerolphosphate Dehydrogenase / Q000378:metabolism*; D006168:Guinea Pigs; D006454:Hemoglobins / Q000032:analysis; D008931:Mitochondria, Muscle / Q000201:enzymology*; D010101:Oxygen Consumption
D003574:Cytochrome c Group; D005420:Flavoproteins; D006454:Hemoglobins; D005993:Glycerolphosphate Dehydrogenase; D003576:Electron Transport Complex IV