6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase: suiting structure to need, in a family of tissue-specific enzymes.
The present review addresses recent advances in research into a family of bifunctional enzymes that are responsible for the twofold task of synthesizing and hydrolyzing fructose-2,6-bisphosphate (Fru-2,6-P2), which in turn regulates the rate of glycolysis in most cells. The structure of the synthetic kinase, conjoined at its carboxyl-terminus to the phosphatase, is very highly conserved throughout evolution and differentiation, with isotypic expression arising from highly variable amino-terminal and carboxyl-terminal regulatory domains. These domains, which frequently contain protein-kinase-catalyzed phosphorylation motifs, are responsible for the widely divergent kinetics observed in various tissues and species, and for the hormonal modulation that alters intracellular levels of Fru-2,6-P2. The present review discusses recent advances in relating structure to function, and the identification of new pathways of transcriptional regulation of this important family of regulatory enzymes.
El-Maghrabi
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MR
Department of Physiology and Biophysics, State University of New York at Stony Brook, Stony Brook, New York 11794-8661, USA. raafat@physiology.pnb.synysb.edu
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D000305:Adrenal Cortex Hormones / Q000502:physiology; D000595:Amino Acid Sequence; D001665:Binding Sites; D001921:Brain / Q000201:enzymology; D005635:Fructosediphosphates / Q000378:metabolism*; D005934:Glucagon / Q000502:physiology; D006019:Glycolysis; D006801:Humans; D007328:Insulin / Q000502:physiology; D007527:Isoenzymes / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008297:Male; D008969:Molecular Sequence Data; D009132:Muscles / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology; D009928:Organ Specificity; D025481:Phosphofructokinase-2 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D013329:Structure-Activity Relationship; D013737:Testis / Q000201:enzymology
D000305:Adrenal Cortex Hormones; D005635:Fructosediphosphates; D007328:Insulin; D007527:Isoenzymes; C027652:fructose 2,6-diphosphate; D005934:Glucagon; D025481:Phosphofructokinase-2