Hexokinase glucose affinity

The principal enzyme catalyzing this reaction, hexokinase, is found in all cells and has a high affinity (low for glucose. 

The substrate specificities of both mammalian and yeast hexo-kinases have been extensively studied (76,77). Nevertheless, work in this area continues both in the search for isoenzyme specific inhibitors and in increasingly detailed investigations of the catalytic mechanism. Recently potential transition state analogs PI-(adenosine-5 )-P3-glucose-6 triphosphate (Ap -glucose) and P1-(adenosine-5 )-P4-glucose-6 triphosphate (Ap.-giucose) were tested as inhibitors of four hexokinase isoenzymes. However, they were found to exhibit less affinity for the enzyme than either of the natural substrates alone (78). 

For fructose to enter the pathways of intermediary metabolism, it must first be phosphorylated (Figure 12.2). This can be accomplished by either hexokinase or fructokinase (also called ketohexo-kinase). Hexokinase phosphorylates glucose in all cells of the body (see p. 96), and several additional hexoses can serve as substrates for this enzyme. However, it has a low affinity (that is, a high Km, see p. 59) for fructose. Therefore, unless the intracellular concentration of fructose becomes unusually high, the normal presence of saturating concentrations of glucose means that little fructose is converted... 

Exley et al. [61] found aluminum in practically all reagents used in a study of the inhibition of hexokinase activity by this element. The way to overcome the problem was cleaning the solutions using an aminophosphonate chelation resin. The procedure reduced the contamination of ATP and NADP to approximately 5% and 10% of their initial values, respectively, but the resin was ineffective in removing aluminum from magnesium acetate or the enzyme glucose 6-phosphate dehydrogenase. Probably the conditions were not favorable for the resin to pick up the aluminum ions from these solutions. It is important to remember that, if there is an affinity between aluminum and the species in solution, a competition between this species and the resin will take place. 

Hexokinase catalyzes the phosphorylation of glucose and fructose by ATP. However the Km for glucose is 0.13 mmol L-1, whereas that for fructose is 1.3 mmol L-1. Assume is the same for both glucose and fructose and the enzyme displays hyperbolic kinetics [Eq. (9.5)]. (a) Calculate the normalized initial velocity of the reaction (i.e., V(/Umax) for each substrate when [S]0 = 0.13, 1.3, and 13.0 mmol L-1. (b) For which substrate does hexokinase have the greater affinity ... 

Glucokinase (GK) has a much lower affinity for glucose than hexokinase therefore it is not fully active at the physiological ranges of blood glucose. Additionally, GK is not inhibited by its product G-6-P, whereas hexokinase is. 

The monosaccharide carriers of Saccharomyces cerevisiae, and also of Kluyveromyces (Saccharomyces) fragilis, appear from polarimetric measurements to have a higher affinity for the a-D anomers of D-glucose, D-mannose, and D-xylose than for the corresponding /3 anomers.178 Intracellularly, a-D-glucopyranose is a slightly better substrate of hexokinase than the /3 anomer.179... 

AR and hexokinase coexist in the eye (and other tissues) and, in principle, compete for the same substrate, D-glucose. Since hexokinase has a much greater affinity for glucose, it will be rapidly converted to the 6-phosphate at physiologically available intracellular levels (such as in the nondiabetic), little or no sorbitol is produced. However, at the excessive sugar levels of the diabetic the ability of the hexokinase present to phos-... 

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