2.0 Fructose and galactose metabolism

Fructose and galactose are metabolized in the liver to produce

glucose,

lactate,

and

fatty acids

Unlike glucose, fructose and galactose do not have a dedicated catabolic pathway.

Instead, cells convert fructose and galactose into glycolytic metabolites and then incorporate them into glycolysis for pyruvate and ATP synthesis.

The catabolism of both fructose and galactose produces

the same number of ATP molecules as glucose.

Fructose is absorbed from the small intestine

and metabolized in the liver, primarily to glycogen.

However, fructose metabolism can also lead to the formation of triglycerides

Fructose metabolism can follow either one of two pathways:

The major pathway of fructose metabolism occurs in the liver, where fructose molecules follow the fructose 1-phosphate pathway initiated by the enzyme fructokinase,

transforming fructose into dihydroxyacetone phosphate and glyceraldehyde 3-phosphate, at which point it merges with the glucose metabolic pathway. 

The utilization of fructose by fructokinase followed by the enzyme aldolase

bypasses the glucokinase and PFK-1 driven steps of glucose metabolism, which are dependent on the hormone insulin

This explains why fructose disappears from blood more rapidly than glucose in diabetic subjects. 

Within the skeletal muscle fructose can transform into fructose 6-phosphate through the enzyme hexokinase,

which can then be directly cycled into the glycolytic pathway.

However, hexokinase has a very low affinity to fructose compared to glucose,

so it is not a significant pathway for fructose metabolism unless elevated levels are expressed in plasma, such as during exercise.

Hereditary defects of fructose metabolism

Essential fructosuria:

Fructose 1,6 biphosphatase deficiency:

Hereditary fructose intolerance:

Essential fructosuria:

Occurring due to a deficiency of fructokinase. A non-serious condition resulting in the loss of  excess accumulated fructose in the urine.

Fructose 1,6 biphosphatase deficiency:

 Resulting in an accumulation of fructose 1,6 biphosphate, this results in the inhibition of glycogenolysis thorough suppression of the activity of phosphorylase. Subjects present with fasting hypoglycaemia.

Hereditary fructose intolerance:

Occurring due to a deficiency of aldolase B, resulting in an accumulation of fructose-1-phosphate (F-1-P). High levels of F-1-P leads to damage of liver and kidney tissues and the inhibition of glycogen phosphorylase, resulting in the inhibition of glycogenolysis and fasting hypoglycaemia.

Galactose, an isomer of glucose, is the sugar in milk,

and infants have an enzyme that metabolizes lactose to galactose and glucose.

In the liver, galactose is converted to G-6-P through the galactose-glucose interconversion pathway

In the liver, galactose is converted to G-6-P through the galactose-glucose interconversion pathway

1. Galactose is phosphorylated by galactokinase to yield galactose-1-phosphate

2. Galactose-1-phosphate is epidimerised to glucose-1-phosphate by the transfer of UDP from uridine diphosphoglucose  by galactose-1-phosphate uridyl transferase.

3. The generated UDP-galactose from step 2 can be epimerized to UDP-glucose by UDP-galactose-4 epimerase

4. Glucose-1-phosphate is then converted to G-6-P via phosphoglucomutase

Galactosemias result in elevated blood galactose

due to an inability of the body to metabolize galactose driven by hereditary defects in galactokinase, uridyltransferase or 4-epimerase.

This can result in:

1. Cataracts (opacity of eye lens): Galactose is reduced in the eye by aldose reductase to form galactitol which accumulates within the lens causing cataracts

2. Liver failure

3. Intellectual disability 

4. Galactosuria - the excretion of galactose in the urine

further reading