Muscle hexokinase

Hepatic hexokinase Muscle glycogen synthetase Muscle phosphorylase Muscle hexokinase Muscle debranching enzyme... 

In the kidney and in muscle tissues, fructose is readily phosphorylated by hexokinase, which, as pointed out above, can utilize several different hexose substrates. The free energy of hydrolysis of ATP drives the reaction forward ... 

L6. Lehto, M., Huang, X., Davis, E. M Le Beau, M. M., Laurila, K. F., Eriksson, K. F., Bell, G. I., and Groop, L., Human hexokinase II gene Exon-intron organization, mutation screening in N1DDM, and its relationship to muscle hexokinase activity. Diabetologia 38, 1466-1474 (1995). 

Hormones have a profound effect on carbohydrate metabolism. Great interest has been aroused by reports of hormonal control of hexokinase activity by specific proteins in animal tissues.99- 100 Hexokinase action is the rate-limiting step in the uptake of D-glucose by muscle. Hexokinase is inhibited in diabetic muscle, but the inhibition can be partially reversed by insulin. A protein fraction from the anterior pituitary gland will inhibit the hexokinase of extracts of brain and muscle, and the effect of this... 

Many examples of product inhibition are to found. Some dehydrogenases are inhibited by NADH (a co-product of the reaction), e.g. PDH and isocitrate dehydrogenase (ICD), which are involved with the glycolysis and the TCA cycle are two such examples. Hexokinase isoenzymes in muscle (but not liver) and citrate synthase are inhibited by their products, glucose-6-phosphate and citrate respectively offering a very immediate fine tuning of reaction rate to match cellular requirements and possibly allowing their substrates to be used in alternative pathways. 

A good example of allosteric inhibition is given by hexokinase (HK) isoenzymes of muscle. The product of the HK reaction, glucose-6-P allosterically inhibits the enzyme, so matching the phosphorylation of glucose to its overall metabolism, helps to regulate... 

Specific activation or inhibition Transport of glucose can be increased or decreased by specihc compounds insulin increases the transport whereas phloridzin, a plant glycoside, inhibits glucose transport by muscle. Insulin increases glucokinase activity in liver, whereas a plant sugar, mannoheptulose, inhibits glucokinase activity. Hexokinase is inhibited by its product, glucose 6-phosphate. 

In the muscle, hexokinase acts on fructose to form fmctose 6-phosphate, which then enters glycolysis. 

King RF, Macfie J, Hill G (1981) Activities of hexokinase, phosphofructokinase, fructose bisphosphatase and 2-oxoglutarate dehydrogenase in muscle of normal subjects and very ill surgical patients. Clin Sci 60 451-456... 

Yet another way to alter the effective activity of an enzyme is to change the accessibility of its substrate. The hexokinase of muscle cannot act on glucose until the sugar enters the myocyte from the blood, and the rate at which it enters depends on the activity of glucose transporters in the plasma membrane. Within cells, membrane-bounded compartments segregate certain enzymes and enzyme systems, and the transport of substrate into these compartments may be the limiting factor in enzyme action. 

Hexokinase Isozymes of Muscle and Liver Are Affected Differently by Their Product, Glucose 6-Phosphate... 

Insulin stimulates the synthesis of hexokinases II and IV, PFK-1, pyruvate kinase, and several enzymes involved in lipid synthesis. Insulin stimulates glycogen synthesis in muscle and liver. 

Figure 9-7 (A) Effect of glucose and glucose 6-phosphate concentrations on reaction rate of yeast hexokinase at equilibrium. Reaction mixtures contain 1-2.2 mM ATP, and 25.6 mM ADP at pH 6.5. From Fromm et al.51 (B) Effect of lactate and pyruvate concentrations on equilibrium reaction rates of rabbit muscle lactate dehydrogenase. Reaction mixtures contained 1.7 mM NAD+, and 30 - 46 pM NADH in Tris-nitrate buffer, pH 7.9, 25°C. From Silverstein and Boyer.53...

Fructose can be metabolized by two routes. In adipose tissue and muscle, hexokinase can phosphorylate fructose to fructose 6-phosphate that then enters glycolysis. In liver, most of the enzyme present is glucokinase not hexokinase and this does not phosphorylate fructose. In this tissue, fructose is metabolized instead by the fructose 1-phosphate pathway. 

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