cDNA sequence and kinetic properties of human lung fructose(1,6)bisphosphatase

A cDNA encoding fructose(1,6)bisphosphatase was isolated from total human l ung RNA. The cDNA contained an open reading frame encoding 337 amino acids. The determined nucleotide sequence of the lung cDNA was significantly diff erent from muscle cDNA and slightly differed from human liver cDNA in a sin gle mutation (Gly-336 for Ala-336) and a T for C substitution in position 6 48. The human lung fructose(1,6)bisphosphatase [Fru(1,6)Pase] was isolated and its kinetic parameters were compared with liver and muscle isoenzymes. Values of k(cat) for the lung Fru(1,6)Pase were lower than for the Liver an d muscle enzyme. Like the liver isoenzyme, lung Fru(1,6)Pase is significant ly less inhibited by AMP than the muscle enzyme. The values of I-0.5 were 9 .5, 9.8, and 0.3 mu M for the liver, lung, and muscle enzyme, respectively. The lung enzyme was slightly more sensitive to fructose(2,6)bisphosphate [ Fru(2,6)P-2] inhibition than the Liver enzyme. K-i was 75 mu M for the lung and 96 mu M for the liver enzyme. The synergistic effect of AMP and Fru(2, 6)P-2 on the lung and liver Fru(1,6)Pase was also observed. In the presence of AMP the corresponding values of K-i for Fru(2,6)P-2 were 16 mu M for th e lung and 10 mu M for the liver enzyme. (C) 1999 Academic Press.