Kinases phosphofructokinase

Mechanism for Gluconeogenesis. Since the glycolysis involves three energetically irreversible steps at the pyruvate kinase, phosphofructokinase, and hexokinase levels, the production of glucose from simple noncarbohydrate materials, for example, pyruvate or lactate, by a reversal of glycolysis ( from bottom upwards ) is impossible. Therefore, indirect reaction routes are to be sought for. 

Kinases, see Adenylate kinase, Hexokinase, Phosphoglycerate kinase, Phosphofructokinase, or Pyruvate kinase Lactate dehydrogenase (Adams et al., 1970)... 

Hexokinase Pyruvate kinase Adenylate kinase Phosphoglycerate kinase Phosphofructokinase Protease inhibitors Pancreatic trypsin inhibitor Soybean trypsin inhibitor Streptomyces subtilisin inhibitor Nucleases... 

ATP Triphosphate Chain Conformation. Much of the work in the area of ATP triphosphate chain conformation has been performed by Cleland and co-workers (14--16). Their studies on metal(III)ATP interactions with kinases have led to the classification of kinases according to the stereochemistry of the polyphosphate chain as it binds to the active site. For the kinases they studied (hexokinase, glycerokinase, creatine kinase, phosphofructokinase, 3-phosphoglycerate kinase, acetate kinase, arginine kinase, adenylate kinase and pyruvate kinase) it was found that B, y-bidentate chromi M(III)-ATP (CrATP) and not a,6,y-tridentate CrATP is a... 

Other isolated enzymes which it has already proved possible to successfully spin label include carbonic anhydrase, creatine kinase, phosphofructokinase, lactate dehydrogenase, liver alcohol dehydrogenase, lysozyme and ribonuclease, as well as the coenzymes NAD and vitamin B12. 

Gluconeogenesis occurs under conditions in which pyruvate dehydrogenase, pyruvate kinase, phosphofructokinase 1, glucokinase, and hexoki-nase are relatively inactive. The low activity of these enzymes prevents futile cycles from occurring and ensures that, overall, pyruvate is converted to glucose. 

Liver Insulin increases the storage of glucose as glycogen in the liver. This involves the insertion of additional GLUT 2 glucose transport molecules in cell walls, increased synthesis of the enzymes pyruvate kinase, phosphofructokinase. and glucokina.se, and the suppression of several other enzymes. Insulin also decreases protein catabolism. 

EXAMPLE 13.10 Both the conversion of fructose 6-phosphate to fructose 1,6-bisphosphate and the reverse-bypass of this reaction in gluconeogenesis are sensitive to the regulatory metabolite fructose 2,6-bisphosphate. This is not an intermediate in either glycolysis or gluconeogenesis but is formed by a separate ATP-dependent kinase, phosphofructokinase-2. 

Figure 5.3 Major control points of glycolysis and the TCA cycle. Enzymes I, hexokinase II, phosphofructokinase III, pyruvate kinase IV, pyruvate dehydrogenase V, citrate synthase VI, aconitase VII, isocitrate dehydrogenase VIII, a-oxoglutarate dehydrogenase.

A decreased glycolytic rate has been proposed as a cause of muscle fatigue and related to pH inhibition of glycolytic enzymes. Decreasing pH inhibits both phosphorylase kinase and phosphofructokinase (PFK) activities. PFK is rate determining for glycolytic flux and therefore must be precisely matched to the rate of ATP expenditure. The essential characteristic of PFK control is allosteric inhibition by ATP. This inhibition is increased by H and PCr (Storey and Hochachka, 1974 ... 

Three nonequilibrium reactions catalyzed by hexoki-nase, phosphofructokinase, and pyruvate kinase prevent simple reversal of glycolysis for glucose synthesis (Chapter 17). They are circumvented as follows ... 

Fructose 2,6-bisphosphate is formed by phosphorylation of fructose 6-phosphate by phosphofructoki-nase-2. The same enzyme protein is also responsible for its breakdown, since it has fructose-2,6-hisphos-phatase activity. This hifrmctional enzyme is under the allosteric control of fructose 6-phosphate, which stimulates the kinase and inhibits the phosphatase. Hence, when glucose is abundant, the concentration of fructose 2,6-bisphosphate increases, stimulating glycolysis by activating phosphofructokinase-1 and inhibiting... 

Figure 19-3. Control of glycolysis and gluconeoge-nesis in the liver by fructose 2,6-bisphosphate and the bifunctional enzyme PFK-2/F-2,6-Pase (6-phospho-fructo-2-kinase/fructose-2,6-bisphosphatase). (PFK-1, phosphofructokinase-1 [6-phosphofructo-1 -kinase] ...

Fig. 2. Representative mutations causing erythroenzymopathies. PK, pymvate kinase G6PD, glu-cose-6-phosphate dehydrogenase PFK, phosphofructokinase.

Where are the control points Reactions catalysed by. Hexokinase/Glucokinase Phosphofructokinase Pyruvate kinase... 

PFK = phosphofructokinase PK = pyruvate kinase G-6-P = glucose-6-phosphate F-6-P = fructose-6-phosphate F-1,6bisP = fructose-1,6 bis phosphate... 

Genetically-determined deficiency of G6PD is the most common cause of haemolysis arising from enzyme defects. Mutated glycolytic enzymes such as hexokinase, phosphofructokinase, aldolase and pyruvate kinase can also bring about haemolysis but the occurrence of these defects are much rarer than for G6PD deficiency (see Case N otes at the end of this chapter). 

Figure 2.6 The process of glycolysis illustrating the three non-eguilibrium reactions. The reactions are catalysed by hexokinase, phosphofructokinase and pyruvate kinase which are indicated by the heavy unidirectional arrows. The reactions in which ATP is utilised and those in which it is produced are indicated (see Appendix 2.7).

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