Fructose kinase

Reactions 1 to 7 take place in the liver and form the major route by which dietary fructose is metabolized other, minor, reactions take place in other tissues. Reaction 1 is catalysed by fructose kinase (EC 2.7.1.4) and reaction 2 by fructose-1-phosphate aldolase. 

Pyruvate kinase possesses allosteric sites for numerous effectors. It is activated by AMP and fructose-1,6-bisphosphate and inhibited by ATP, acetyl-CoA, and alanine. (Note that alanine is the a-amino acid counterpart of the a-keto acid, pyruvate.) Furthermore, liver pyruvate kinase is regulated by covalent modification. Flormones such as glucagon activate a cAMP-dependent protein kinase, which transfers a phosphoryl group from ATP to the enzyme. The phos-phorylated form of pyruvate kinase is more strongly inhibited by ATP and alanine and has a higher for PEP, so that, in the presence of physiological levels of PEP, the enzyme is inactive. Then PEP is used as a substrate for glucose synthesis in the pathway (to be described in Chapter 23), instead... 

As discussed in Section 22.7, illumination of chloroplasts leads to light-driven pumping of protons into the thylakoid lumen, which causes pH changes in both the stroma and the thylakoid lumen (Figure 22.27). The stromal pH rises, typically to pH 8. Because rubisco and rubisco activase are more active at pH 8, COg fixation is activated as stromal pH rises. Fructose-1,6-bisphosphatase, ribulose-5-phosphate kinase, and glyceraldehyde-3-phosphate dehydrogenase all have alkaline pH optima. Thus, their activities increase as a result of the light-induced pH increase in the stroma. 

Transfer of the phosphoryl group to ADP in step 10 then generates ATP and gives enolpyruvate, which undergoes tautomerization to pyruvate. The reaction is catalyzed by pyruvate kinase and requires that a molecule of fructose 1,6-bis-phosphate also be present, as well as 2 equivalents of Mg2+. One Mg2+ ion coordinates to ADP, and the other increases the acidity of a water molecule necessary for protonation of the enolate ion. 

Pilkis SJ et al 6-Phosphofructo-2-kinase/fructose-2,6-bisphospha-tase A metabolic signaling enzyme. Annu Rev Biochem 1995 64 799. 

Pyruvate kinase T T Insulin, fructose Glucagon (cAMP) Fructose 1,6-bisphosphate, insulin ATP, alanine, glucagon (cAMP), epinephrine... 

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] ...

Pyruvate kinase (PK) is one of the three postulated rate-controlling enzymes of glycolysis. The high-energy phosphate of phosphoenolpyruvate is transferred to ADP by this enzyme, which requires for its activity both monovalent and divalent cations. Enolpyruvate formed in this reaction is converted spontaneously to the keto form of pyruvate with the synthesis of one ATP molecule. PK has four isozymes in mammals M, M2, L, and R. The M2 type, which is considered to be the prototype, is the only form detected in early fetal tissues and is expressed in many adult tissues. This form is progressively replaced by the M( type in the skeletal muscle, heart, and brain by the L type in the liver and by the R type in red blood cells during development or differentiation (M26). The M, and M2 isozymes display Michaelis-Menten kinetics with respect to phosphoenolpyruvate. The Mj isozyme is not affected by fructose-1,6-diphosphate (F-1,6-DP) and the M2 is al-losterically activated by this compound. Type L and R exhibit cooperatively in... 

How does phosphorylation affect the activity of phosphofructo-2-kinase (PFK-2), the enzyme that synthesizes fructose 2,6-bisphosphate, a regulator of glycolysis There are two possible answers it either activates it or inactivates it. The simplest approach to the question is just to flip a coin. You should stand a 50 50 chance of getting it right. The next simplest way is to figure it out. 

Fructose 2,6-bisphosphate stimulates glycolysis by allosterically activating phosphofructo-1-kinase (PFK-1). First, decide what should... 

There s also a fructose 2,6-bisphosphatase that hydrolyzes fructose 2,6-bisphosphate see if you can figure out what happens to the phosphatase activity in liver and muscle when the enzyme is phosphorylated. As a check to your answer, you might recall the PFK-2 and fructose 2,6-bisphosphatase are one and the same protein. Phosphorylation-dephosphorylation actually shifts the activity of this single protein between the kinase and the phosphatase. So the answer you get should be opposite to the one we got earlier. 

In contrast to kinases, phosphatases catalyse the removal of phosphoryl groups, again, either from phosphorylated metabolites such as glucose-6-phosphate or fructose-1,6-bisphosphate... 

Feed-forward control is more likely to be focused on a reaction occurring at or near the end of a pathway. Compounds produced early in the pathway act to enhance the activity of the control enzyme and so prevent a back log of accumulated intermediates just before the control point. An example of feed-forward control is the action of glucose-6-phosphate, fructose-1,6-bisphosphate (F-l,6bisP) and phosphoenol pyruvate (PEP), all of which activate the enzyme pyruvate kinase in glycolysis in the liver. 

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... 

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