Nutrition and Physical Activity Iron Deficiency: Improved Exercise Performance Within 15 Hours of Iron Treatment in Rats1 WAYNE T. WILLIS, KISHOR GOHIL, * GEORGE A. BROOKS* AND PETER R. DALLMAN University of California, San Francisco Medical Center, Department of Pediatrics, School of Medicine, San Francisco, CA 94143 and *university of California, Berkeley, Exercise Physiology Laboratory, Department of Physical Education, Berkeley, CA 94720 ABSTRACT We tested the hypothesis that a very rapid improvement in exercise performance of iron-de ficient rats after treatment with iron might reveal a rate-limiting role of ionic iron as an enzyme cofactor in energy metabolism. Rats were given iron-deficient or control diets after weaning at 21 d of age and in- traperitoneal iron dextran (50 mg/kg) at 45 d of age. Time to fatigue during an easy walking exercise (en durance) was measured 15 and 18 h after iron dextran or saline injection. Endurance increased more than threefold compared to the saline-treated, iron-deficient animals without a significant change in hemoglobin concentration. This prompt improvement suggests that lack of cofactor iron might play a metabolically important role in impairing exercise performance in the severely iron-deficient rat. J. Nutr. 120:909-916, 1990. INDEXING KEY WORDS: •exercise •energy metabolism •irondeficiency •rat Iron deficiency impairs work capacity in humans and rats (1). This impairments results partly from a decrease in the concentration of hemoglobin (Hb) that restricts the capacity of the blood for carrying oxygen from the lungs to the tissues. The role of anemia in iron-deficient rats has previously been studied by correcting only the anemia by means of exchange transfusion (2, 3). The degree to which work capacity improves after transfu sion indicates the specific role of Hb, and any deficit that remains can be assumed to be due to other iron-related factors. Among these other factors, the mitochondria! iron enzymes of the electron transport chain have re ceived the most attention (2-7). Iron is an integral part of the cytochromes and iron-sulfur proteins that are required for the oxidative phosphorylation of ADP to ATP. The role of these iron compounds in work perfor mance was indicated by impaired muscle contraction in the isolated, perfused hind limb of iron-deficient rats (5). In addition, the relatively slow improvement in work performance under various conditions of treadmill ex ercise after administration of iron to iron-deficient rats corresponded to the rate of increase in muscle oxidative enzyme activity and thereby suggested a distinct role for the iron-containing mitochondrial electron transport enzymes (2, 5, 8). Iron that is not an integral part of a protein but that is required as an enzyme cofactor also is involved in energy metabolism, but the possible contribution of such a role to the impaired work capacity of iron defi ciency is difficult to ascertain directly. Recent experi ments from our laboratories suggested that ionic iron might result in an improved tricarboxylic acid (TCA) cycle flux in skeletal muscle within only 16 h of treating iron-deficient rats with iron dextran (9). We concluded that this result might be associated with a prompt increase in the activity of aconitase hydratase, the only enzyme of the TCA cycle that requires ionic iron as a cofactor (10). Other recent experiments from our laboratories showed that the rate of gluconeogenesis in isolated hepatocytes was decreased in rats with severe iron defi ciency (11). One possible explanation for this observa tion is a decrease in activity of phosphoenolpyruvate carboxykinase (PEPCK), which catalyzes the first and rate-limiting step in gluconeogenesis. This enzyme is unusual in its requirement for a specific ferroactivator protein as well as for Fe2t (12,13). The activity of PEPCK normally doubles within 2 h in response to exercise (14). Although iron deficiency has not been found to signifi cantly decrease either the activity of PEPCK in vitro (11) or the concentration of ferroactivator protein (15), there might be inadequate intracellular ionic iron for the 'Supported by National Institutes of Health grant DK-13897 and American Heart Association grant 860879. 0022-3166/90 $3.00 ©1990American Institute of Nutrition. Received 19 September 1989.Accepted 13 February 1990. 909 by guest on April 18, 2012 jn.nutrition.org Downloaded from