Phosphofructokinases (PFK; EC 2.7.1.11) are tetrameric enzymes that have a key role in the regulation of glycolysis; as such, they are subject to allosteric activation and inhibition by various metabolites. Eukaryotic PFKs are about twice the size of prokaryotic enzymes and are regulated by a wider repertoire of effectors: for example, the subunit molecular weights of rabbit muscle (RM) PFK and Bacillus stearothermophilus (Bs) PFK are 82,000 and 36,000, respectively. Both enzymes are activated by ADP (or AMP), but RM-PFK is also activated by fructose bisphosphates (FBP) and inhibited by ATP and citrate. This, together with other evidence, has led to speculation that mammalian PFKs have evolved by duplication of a prokaryotic gene, although previous peptide analysis failed to reveal internal homology in RM-PFK. Here we demonstrate clear homology among the N- and C-halves of RM-PFK and Bs-PFK, thus establishing an evolutionary relationship by series gene duplication and divergence. Furthermore, detailed knowledge of the Bs-PFK structure provides the basis for inferences concerning the structural organization of RM-PFK and the evolution of new effector sites in the enzyme tetramer.

Amino Acid Sequence↗

PubMedDate not supplied

Cyclic 3',5'-adenosine monophosphate phosphodiesterase in the thymus of normal and leukemic mice.

Changes in the cyclic AMP phosphodiesterase of the thymus were observed during leukemogenesis in the AKR mouse. Upon maturation, activity at 1.0 muM and 100 muM cyclic AMP concentrations decreased in both the AKR mouse and normal Swiss mice. The thymus of the leukemic mouse had sharply higher phosphodiesterase activity. Much of the phosphodiesterase activity of normal and leukemic mice was associated with particulate fractions, and, as indicated by marker enzymes for particulate components, the high affinity phosphodiesterase was enriched in a fraction containing plasma membranes.

3',5'-Cyclic-AMP Phosphodiesterases↗