Biochemical Aberrations in Otosclerosis: Activity and Control of Phosphofructokinase from Human Ossicles

Abstract

Phosphofructokinase activity was determined in extracts from ossicles of otosclerotic and non-otosclerotic individuals. The assay was varied to determine the influence of adenosine triphosphate and citrate on bone phosphofructokinase activity, especially in otosclerotic stapedes. Phosphofructokinase from ossicles is not inhibited by levels of adenosine triphosphate which normally inhibit the enzyme from skeletal muscle, heart, liver and brain tissue. The phosphofructokinase activity in stapedes is greater than the other ossicles, but the activity from otosclerotic stapedes is similar to the activity from non-otosclerotic controls. However, otosclerotic stapedes phosphofructokinase responds differently and with less sensitivity to increasing citrate concentrations than non-otosclerotic controls. Glucose-6-phosphate, replacing fructose-6-phosphate in the phosphofructokinase reaction mixture, yields rates similar to fructose-6-phosphate, indicating hexose isomerase is functioning to the same capacity in otosclerotic and non-otosclerotic tissues. Further, the use of glucose-6-phosphate with no difference in reaction rates suggests that sufficient substrate is available for a fully active phosphofructokinase in otosclerosis. The results obtained were used to relate phosphofructokinase abnormalities to enzyme differences previously observed in otosclerosis.