Hexokinase-catalyzed reactions

Hexokinase catalyzes the phosphorylation of glucose from ATP, yielding glncose-6-P and ADR Using the values of Table 3.3, calculate the standard-state free energy change and equilibrium constant for the hexokinase reaction. 

When (1) and (2) are coupled in a reaction catalyzed by hexokinase, phosphorylation of glucose readily proceeds in a highly exergonic reaction that under physiologic conditions is irreversible. Many activation reactions follow this pattern. 

Allow for consumption of ATP by reactions catalyzed by hexokinase and phosphofructokinase... 

The third indirect route involves the formation of free glucose from glucose 6phosphate by circumventing the hexokinase reaction. This route is catalyzed by... 

As bacterial transglucosidase is instrumental in the transfer of a D-glucose residue from one acceptor to another, so does yeast hexokinase 3 catalyze a transphosphorylation. The highly specific donator of a labile phosphate group is adenosine triphosphate (XX), the fermentable hexoses D-glucose, D-mannose and D-fructose functioning as acceptors. Hexokinase catalyzes the reaction... 

Haldane relationships can also be useful in characterizing isozymes or the same enzyme isolated from a different source. Reactions catalyzed by isozymes must have identical equilibrium constants, but the magnitudes of their kinetic parameters are usually different (e.g., the case of yeast and mammalian brain hexokinase ). Note that the Haldane relationship for the ordered Bi Bi mechanism is = Hmax,f p i iq/(f max.r ia b)- This same... 

Figure 2. (A) Effect of simultaneously raising the absolute concentrations of ATP and ADP on the indicated equilibrium exchange reactions catalyzed by yeast hexokinase. (B) Effect of simultaneously raising the absolute concentrations of glucose and glucose 6-phosphate on the indicated equilibrium exchange reactions of yeast hexokinase.

We have seen how [S] affects the rate of a simple enzymatic reaction (S—>P) with only one substrate molecule. In most enzymatic reactions, however, two (and sometimes more) different substrate molecules bind to the enzyme and participate in the reaction. For example, in the reaction catalyzed by hexokinase, ATP and glucose are the substrate molecules, and ADP and glucose 6-phosphate are the products ... 

This reaction, which is irreversible under intracellular conditions, is catalyzed by hexokinase. Recall that kinases are enzymes that catalyze the transfer of the terminal phosphoryl group from ATP to an acceptor nucleophile (see Fig. 13-10). Kinases are a subclass of transferases (see Table 6-3). The acceptor in the case of hexokinase is a hexose, normally D-glucose, although hexokinase also catalyzes the phosphorylation of other common hexoses, such as D-fructose and D-mannose. 

After the protection of its DNA from damage, perhaps nothing is more important to a cell than maintaining a constant supply and concentration of ATP. Many ATP-using enzymes have Km values between 0.1 and 1 mM, and the ATP concentration in a typical cell is about 5 mM. If [ATP] were to drop significantly, the rates of hundreds of reactions that involve ATP would decrease, and the cell would probably not survive. Furthermore, because ATP is converted to ADP or AMP when spent to accomplish cellular work, the [ATP]/[ADP] ratio profoundly affects all reactions that employ these cofactors. The same is true for other important cofactors, such as NADH/NAD"1" and NADPH/NADP+. For example, consider the reaction catalyzed by hexokinase ... 

The four forms of hexokinase found in mammalian tissues are but one example of a common biological situation the same reaction catalyzed by two or more different molecular forms of an enzyme. These multiple forms, called isozymes or isoenzymes, may occur in the same species, in the same tissue, or even in the same cell. The different forms of the enzyme generally differ in kinetic or regulatory properties, in the cofactor they use (NADH or NADPH for dehydrogenase isozymes, for example), or in their subcellular distribution (soluble or membrane-bound). Isozymes may have similar, but not identical, amino acid sequences, and in many cases they clearly share a common evolutionary origin. 

The reaction catalyzed by hexokinase. Attack on the terminal phosphorus atom of ATP is probably facilitated by proton removal by a negatively charged group in the catalytic site of the enzyme ( B in the figure). It is also facilitated by the fact that the terminal phosphate of ATP is an excellent leaving group. 

The reaction catalyzed by phosphofructokinase. The mechanism of this reaction is very similar to the hexokinase reaction shown in figure 12.16. B is a proton acceptor at the active site. 

Fig. 6.—Hypothetical Model for the Biosynthesis of Cellulose.184 [Numbers refer to reactions catalyzed by the following enzymes 1, invertase (EC 3.2.1.26) 2, sucrose synthetase 3, hexokinase (EC 2.7.1.1) 4, phosphoglucomutase (EC 2.7.5.1) 5, UDP-glucose pyrophosphorylase and 6, 7, and 8, hypothetical reactions in the pathway to cellulose.]...

Three examples of coupled reactions will be considered here more coupled reactions are discussed in the literature (7). The first is the transferase reaction catalyzed by hexokinase ... 

Phosphoryl transfer is a fundamental reaction in biochemistry and is one that was discussed in mechanistic and structural detail earlier (Section 9.4). Kinases are enzymes that catalyze the transfer of a phosphoryl group from ATP to an acceptor. Hexokinase, then, catalyzes the transfer of a phosphoryl group from ATP to a variety of six-carbon sugars (hexoses), such as glucose and mannose. Hexokinase, like adenylate kinase (Section 9.4.2) and all other kinases,... 

As discussed above, an enzymatic reaction is usually found to be more rapid in one direction than the other so that the reaction is virtually irreversible.If the product of the reaction in one direction is removed as it is formed (Le., because it is the substrate of a second enzyme present in the reaction mixture), the equilibrium of the first enzymatic process is displaced so that the reaction may continue to completion in that direction. Reaction sequences in which the product of one enzyme-catalyzed reaction becomes the substrate of another enzyme, often through many stages, are characteristic of metabolic processes. Analytically, several enzymatic reactions also may be Unked together to provide a means of measuring the activity of the first enzyme or the concentration of the initial substrate in the chain. For example, the activity of creatine kinase is usually measured by a series of linked reactions, and glucose can be determined by consecutive reactions catalyzed by hexokinase and glucose-6-phosphate dehydrogenase. 

The conversion of fructose-1-phosphate into glycolytic intermediates bypasses two regulatory steps (the reactions catalyzed by hexokinase and PFK-1) thus fructose is metabolized more quickly than glucose. 

The enzyme hexokinase, which catalyzes the phosphorylation of glucose, is allosterically inhibited by the product of the reaction it catalyzes, glucose-6-phosphate. A buildup of this product indicates that the reactions of glycolysis are not proceeding at a rapid rate, presumably because the energy demands of the cell are being met. 

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