Abnormal muscle fructose bisphosphatase activity in malnourished cancer patients.

Abstract

Malnourished patients without cancer have abnormal glucose metabolism, low activities of the key enzymes of glycolysis in muscle, and abnormal muscle fiber-type distribution. Malnutrition in cancer is also associated with altered glucose metabolism, and therefore muscle enzyme activities and fiber types were measured in 17 malnourished patients with gastrointestinal cancer (weight loss, 18.1% +/- 7.9 SD). These patients were matched with 17 depleted noncancer patients (weight loss, 22.8% +/- 10.25 SD) and 17 normal controls. Results of in vitro measurement of the maximal activity of phosphofructokinase (PFK), hexokinase (HK), and oxogluterate dehydrogenase (OGD) were similar in both undernourished groups and lower than that of normal controls. Both groups also had reduced Type II fiber size and number. The activity of fructose bisphosphatase (FBP) was significantly higher in cancer patients (0.62 mu ml min-1 g +/- 0.26 SD) than in noncancer patients (0.39 +/- 0.15), but similar to that in controls (0.65 +/- 0.29). As FBP is involved in substrate cycling, inappropriately high activity reflects an inability to adapt to malnutrition that could lead to high rates of cycling and wasteful energy expenditure at times of maximal activation of the cycle.