The Fructose 1,6-Diphosphatase-Phosphofructokinase Substrate Cycle

Rat liver phosphofructokinase: kinetic activity under near-physiological conditions

“…Their results indicate that PFK turnover increases from 0.13 (4%) to 0.84 /imol/(min g) (25%) as extracellular glucose is raised from 5.5 to 27.4 mM. Even under highly glucoenogenic conditions, such as with dihydroxyacetone as the substrate, Clark et al (1974) found PFK turnover of 0.16 mmol/(min g) or 5% of the available PFK activity.…”

“…Rates of glycolysis give a lower limit to the functional activity of PFK in the cell. However, actual PFK turnover in the cell most likely exceeds the rate of glycolysis since significant "substrate cycling" is thought to occur between the PFK and FBPase reactions in the liver (Clark et al, 1974). Also, the measurement of lactate and pyruvate production generally underestimates the rate of glycolysis because of their continued metabolism.…”

“…It appears, therefore, that in isolated perfused liver or liver cells, PFK turnover varies in a range from a minimum of 4% to a maximum of at least 25% of the total PFK activity available. This activity is achieved with F6P levels ranging from 0.01 mmol/g in the cells of Clark et al (1974) to as high as 0.1 mmol/g found in fed livers (Bergmeyer, 1974). Clearly, the affinity of PFK for F6P in the cell is significantly greater than that permitted by the average cellular concentration of MgATP (3 mM) on the assayable enzyme activity as indicated in Figure 4A.…”

Role of enzyme interactions in the regulation of gluconeogenesis: phosphorylation of fructose 1,6-bisphosphatase and phosphofructokinase by kidney protein kinase

“…Thus, in tissues such as kidney and liver, where both enzymes are present in the cytosol, the activities may be regulated in such a manner that only fructose 1,6-bisphosphatase is active during gluconeogenesis. A number of independent studies have now shown that there is little or no "futile cycling" and very low rates of glycolysis during active gluconeogenesis in these tissues (Soling et al, 1973;Clark et al, 1974;Hue & Hers, 1974a,b).…”