Gluconeogenesis Hexokinase

Mechanism for Gluconeogenesis. Since the glycolysis involves three energetically irreversible steps at the pyruvate kinase, phosphofructokinase, and hexokinase levels, the production of glucose from simple noncarbohydrate materials, for example, pyruvate or lactate, by a reversal of glycolysis ( from bottom upwards ) is impossible. Therefore, indirect reaction routes are to be sought for. 

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 ... 

Seven of the reactions of glycolysis are reversible and are used for gluconeogenesis in the liver and kidneys. Three reactions are physiologically irreversible and must be circum vented. These reactions are catalyzed by the glycolytic enzymes pyruvate kinase, phos phofructokinase, and hexokinase. 

These considerations do not take into account the major glycolytic controls exerted by the hexokinase-phosphofructokinase system (230) but they do show that G-3PDH could act as a regulatory enzyme in response to the NAD+ NADH and ATP ADP X Pi ratios in the cell. These ratios in conjunction with appropriate substrate (i.e., G-3P, DPGA, and Pi) concentrations prime the enzyme for glycolysis or gluconeogenesis in accord with the particular environment and needs of the cell. 

Four enzymes are unique to the process of gluconeogenesis and are required to circumvent the unidirectional steps of glycolysis (Fig. 13.1). Two of these are pyruvate carboxylase, which converts pyruvate to oxaloacetate, and PEP carboxykinase, which converts oxaloacetate to phosphoenolpyruvate. These enzymes are required to effectively reverse the action of pyruvate kinase. The other two are fructose-1,6-bisphosphatase and glucose-6-phosphatase, which effectively reverse the actions of PFK and hexokinase or glucokinase. 

There are three reactions that are counter-productive relative to gluconeogenesis. These are pyruvate kinase, PFK I, and glucokinase (or hexokinase). 

The third bypass is the final reaction of gluconeogenesis, the dephosphorylation of glucose 6-phosphate to yield glucose (Fig. 14-16). Reversal of the hexokinase reaction (p. 526) would require phosphoryl group trans-... 

Mannose is a monosaccharides. Containing six carbons and an aldehyde group, it is classified as an aldose and a hexose. Mannose is a constituent of glycoproteins and a few polysaccharides. Mannose is phosphorylated by hexokinase to mannose-6-phosphate, which is readily isomerized to fructose-6-phosphate for entry into glycolysis or gluconeogenesis (Figure 13.12). 

Hexokinase is not involved in the process of gluconeogenesis. Instead, the enzyme glucose-6-... 

---