Glucokinase in liver

Glycogenesis begins with the phosphorylation of glucose by glucokinase in liver and by hexokinase in muscle and other tissues (Chapter 13) ... 

Glucokinase (induced by insulin in liver), hexokinase (peripheral tissues) PFK-1 (rate-limiting)... 

Figure 3.23 A sequence of processes explaining the role of glucokinase in the liver and fi-cells in regulation of the blood glucose concentration. The increase in the plasma insulin increases glucose uptake by muscle and decreases fatty acid mobilisation from adipose tissue which lowers the plasma fatty acid level which also increases glucose uptake (Chapter 12).

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. 

The glucose concentration is the major factor regulating glycogen synthesis in liver. Glucose activates glucokinase directly as a substrate and indirectly via an increase in the concentration of fructose 6-phosphate. It also activates glycogen synthase but it inhibits glycogen phosphorylase (see text). 

The pathway for gluconeogenesis is shown in Figures 6.23 and 6.24. Some of the reactions are catalysed by the glycolytic enzymes i.e. they are the near-equilibrium. The non-equilibrium reactions of glycolysis are those catalysed by hexokinase (or glucokinase, in the liver), phosphofructokinase and pyruvate kinase and, in order to reverse these steps, separate and distinct non-equilibrium reactions are required in the gluconeogenic pathway. These reactions are ... 

Different responses of isozymes to allosteric modulators. This difference is useful in fine-tuning metabolic rates. Hexokinase IV (glucokinase) of liver and the hexokinase isozymes of other tissues differ in their sensitivity to inhibition by glucose 6-phosphate. 

In the liver cell, the enzymes are spatially separated Glucokinase in the cytosol and glucose-6-phosphatase in the endoplasmic reticulum. Does this separation influence the futile cycle ... 

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. 

Not only is glycolysis in all cells controlled by these three enzymes, but if the cell is in a high-energy state, or if glucose is plentiful, or both, the excess glucose is not degraded by other tissues but is selectively captured via glucokinase in the liver, where it is stored (Sec. 11.5). 

Hariharan, N., Farrelly, D Hagan, D., Hillyer, D., Arbeeny, C-, Sabrah, T, Trcloar, A., Brown, K Kalinowski, S., and Mookhtiar, K, (1997). Expression of human hepatic glucokinase in transgenic mice liver results in decreased glucose levels and reduced body weight. Diabetes 46, 11-16. 

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