Biological Chemistry - Berezov, T. T., Korovkin, B. F. 1998

Carbohydrate Metabolism
Glycolysis
Incorporation of Other Carbohydrates into the Glycolytic Pathway

Fructose. It has been established that free fructose found in many fruits, as well as formed from sucrose in the Small Intestine, can be absorbed by Tissues and phosphorylated to fructose-6-phosphate by hexokinase in the presence of ATP:

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This reaction is inhibited by glucose. The resulting fructose-6-phosphate is either converted into glucose through the stages of glucose-6-phosphate formation and subsequent Cleavage of phosphoric acid (Fig. 10.4), or undergoes further transformations. Fructose-6-phosphate is converted into fructose-1,6-bisphosphate by 6-Phosphofructokinase and ATP:

Subsequently, fructose-1,6-bisphosphate can undergo further transformations via the Glycolysis pathway. This is the main pathway for the incorporation of fructose into the METABOLISM of Muscle tissue, Kidneys, and adipose tissue.

In the Liver, however, a different pathway exists. The liver contains the enzyme fructokinase, which catalyzes the phosphorylation of fructose not at the 6th, but at the 1st carbon atom:

This reaction is not blocked by glucose. The resulting fructose-1-phosphate is then cleaved by ketose-1-phosphate aldolase into dihydroxyacetone phosphate and D-glyceraldehyde:

The resulting D-glyceraldehyde is phosphorylated to glyceraldehyde-3-phosphate by the corresponding kinase (triokinase). Dihydroxyacetone phosphate is also converted into this same glycolytic intermediate.

There is an inherited disorder of Fructose Metabolism known as essential fructosuria, which is associated with a congenital deficiency of fructokinase, meaning the body fails to produce fructose-1-phosphate. As a result, fructose metabolism can proceed only via phosphorylation to fructose-6-phosphate; however, this reaction is inhibited by glucose, causing fructose to accumulate in the Blood. The "renal threshold" for fructose is very low, which is why fructosuria is detected even at a blood fructose concentration of 0.73 mmol/L.

Fig. 10.4. Fructose metabolism.

1 - hexokinase; 2 - 6-phosphofructokinase; 3 - fructose bisphosphate aldolase; 4 - ketohexokinase; 5 - ketose-1-phosphate aldolase; 6 - triokinase; 7 - glucose phosphate isomerase; 8 - glucose-6-phosphatase; 9 - Triosephosphate isomerase.

Fig. 10.5. Galactose Metabolism.

Galactose. The primary source of galactose is dietary lactose, which is hydrolyzed into galactose and glucose in the digestive tract (Fig. 10.5).

Galactose metabolism begins with its conversion into galactose-1-phosphate. This reaction is catalyzed by galactokinase in the presence of ATP:

In the next reaction, in the presence of UDP-glucose, the enzyme hexose-1-phosphate uridylyltransferase catalyzes The conversion of galactose-1-phosphate into glucose-1-phosphate, simultaneously yielding uridine diphosphate galactose (UDP-galactose):

The resulting glucose-1-phosphate is subsequently either converted into glucose-6-phosphate and undergoes already familiar transformations, or forms free glucose under the action of phosphatase, while UDP-galactose undergoes a rather unique epimerization:

Then, UDP-glucose pyrophosphorylase catalyzes the cleavage of UDP-glucose to form glucose-1-phosphate:

For further transformations of glucose-1-phosphate, see above.

One of the pathological conditions resulting from impaired Carbohydrate Metabolism is galactosemia, a recessively inherited disorder. In this condition, the total blood monosaccharide level increases primarily due to elevated galactose, reaching 11.1–16.6 mmol/L. Blood glucose concentration does not change significantly. In addition to galactose, galactose-1-phosphate also accumulates in the blood. Galactosemia leads to intellectual disability and lenticular cataracts. The onset of this disease in newborns is associated with a deficiency of the enzyme hexose-1-phosphate uridylyltransferase. With age, a weakening of this specific carbohydrate metabolism disorder is observed.