Glucose Production by the Liver and Kidneys


The biosynthesis of glucose from pyruvate, lactate, or other precursors is known as gluconeogenesis. It is not a direct reversal of glycolysis, since several steps of glycolysis are irreversible. Gluconeogenesis occurs mainly in the liver and less so in the kidney. These tissues contain all the necessary enzymes for gluconeogenesis and, furthermore, for the enzymatic activity of glycerol kinase, which allows glycerol to enter the gluconeogenic pathway at the level of glyceraldehyde 3-phosphate (Figure 2).

It is vital that the organism synthesizes glucose for those tissues that are unable to synthesize glucose. In humans, liver glycogen stores can sustain the body for 18 h without the ingestion of dietary carbohydrates. After this period, the liver must produce glucose for transport to other organs. The liver is the main gluconeogenic contributor (90%), while the kidney contributes gluconeogenically produced glu-

Glucose t

Glucose 6-phosphate

Fructose 6-phosphate t

Fructose 1,6-bisphosphate r h acetone^ + Glyceraldethyde

, , . 3-phosphate phosphate

1,3-Bisphospho glycerate

3-Phospho glycerate

Glycerol 3-phosphate

2-Phospho glycerate


Phosphoenol pyruvate t

Oxaloacetate t

Malate t

Pyruvate !


Figure 2 Outline of gluconeogenesis.

cose to a lesser extent (10%).


Glycogen is a branched polymer of glucose, which contains as many as 100 000 glucose units. The breakdown of glycogen for the production of glucose is known as glycogenolysis. Glycogen breakdown is initiated at the nonreducing ends of its branches. It consists of phosphorolysis of single glucose units by the cooperating enzymatic action of glycogen phos-phorylase and the debranching enzyme. The product of phosphorolysis, glucose 1-phosphate, needs the additional action of phosphoglucomutase to convert it to glucose 6-phosphate. The liver contains the enzyme glucose 6-phosphatase for the hydrolysis of glucose 6-phosphate to free glucose, which can then be exported to the target tissues. However, the muscle and brain do not contain this enzyme, and the glucose 6-phosphate they produce enters the glycolytic pathway for energy production. Glycogen is a very efficient storage from of glucose, having an overall efficiency of storage of approximately 97%.

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