Cold-sensitive cytosolic 3,5,3'-triiodo-L-thyronine-binding protein and pyruvate kinase from human erythrocytes share similar regulatory properties of hormone binding by glycolytic intermediates.
Similar cold-sensitive properties, values of dissociation constants (Kd = 1 x 10(-10) M), and regulatory effectors were found for the cold-sensitive cytosolic 3,5,3'-triiodo-L-thyronine (L-T3)-binding protein (CTBP) and pyruvate kinase from human erythrocyte. Various metabolites of the blood cell were assayed for their effects on CTBP activity after heat and cold preincubation treatments. Among these compounds, five- and six-carbon phosphorylated sugars were effective in protecting the CTBP activity against cold inactivation, whereas only ATP and dATP blocked activation by heat treatments. The effects of fructose 1,6-bisphosphate, fructose 2,6-bisphosphate, and ATP were obtained at physiological concentrations. Three-carbon phosphorylated intermediates of glycolysis, ADP, AMP, cAMP, and GTP had no effect on cold and heat treatments. The monomer-tetramer interconversion of the enzyme was also regulated by fructose 1,6-bisphosphate and ATP. The association is under the control of fructose 1,6-bisphosphate, whereas the dissociation is under ATP control. This regulation may have physiological relevance since the hormone binds to the tetrameric form of the enzyme at a site other than the active site.
Fanjul
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Departamento de Bioquímica de la Nutrición, Universidad Nacional de Tucumán, Argentina.
Farías
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RN
D000255:Adenosine Triphosphate / Q000494:pharmacology; D002241:Carbohydrates / Q000494:pharmacology; D002352:Carrier Proteins / Q000097:blood* / Q000187:drug effects; D003080:Cold Temperature; D003600:Cytosol / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism*; D005635:Fructosediphosphates / Q000494:pharmacology; D006019:Glycolysis; D006801:Humans; D007700:Kinetics; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000097:blood* / Q000187:drug effects; D011770:Pyruvate Kinase / Q000097:blood*; D012265:Ribonucleotides / Q000494:pharmacology; D013963:Thyroid Hormones; D014284:Triiodothyronine / Q000097:blood*; D000097810:Thyroid Hormone-Binding Proteins
D000255:Adenosine Triphosphate; D002241:Carbohydrates; D002352:Carrier Proteins; D005635:Fructosediphosphates; D046911:Macromolecular Substances; D008565:Membrane Proteins; D011770:Pyruvate Kinase; D012265:Ribonucleotides; D013963:Thyroid Hormones; D014284:Triiodothyronine; D000097810:Thyroid Hormone-Binding Proteins; C029063:fructose-1,6-diphosphate