title: Three pyruvate kinase variants with increased affinity for PEP.
abstract: Three variants of pyruvate kinase are described which have marked reduction of activity associated with severe non-spherocytic haemolytic anaemia. Each variant shows a reduced K0.5 PEP (the value of the intercept of the abscissa on the Hill plot) and reduced Hill coefficient; FDP activation and ATP inhibition are less than normal and utilization of GDP is increased. The variants are slightly less inhibited by 2,3DPG than controls but require more FDP to relieve this inhibition. Cases 1 and 2 have decreased thermostability but case 3 is normal. The mutant enzymes are further distinguished by their affinity for FDP. Their kinetic and physicochemical properties are compared with other known cases with high affinity for PEP and discussed in terms of a R in equilibrium to T model model for allosteric enzymes.
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000328:Adult; D000746:Anemia, Hemolytic, Congenital Nonspherocytic / Q000097:blood / Q000201:enzymology*; D002648:Child; D004163:Diphosphoglyceric Acids / Q000494:pharmacology; D004789:Enzyme Activation; D005260:Female; D005635:Fructosediphosphates / Q000378:metabolism; D014644:Genetic Variation; D006801:Humans; D010375:Pedigree; D010728:Phosphoenolpyruvate / Q000378:metabolism; D011770:Pyruvate Kinase / Q000037:antagonists & inhibitors / Q000097:blood / Q000172:deficiency / Q000235:genetics*
chemical_list: D004163:Diphosphoglyceric Acids; D005635:Fructosediphosphates; D010728:Phosphoenolpyruvate; D000255:Adenosine Triphosphate; D011770:Pyruvate Kinase