A: About a baby with Fructose Intolerance (C-02)


Original question 

 

Short answer: (f)

 

Sucrose or table sugar is a disaccharide formed by glucose and fructose. When digested in the small intestine by the action of sucrose, glucose and fructose are released. For the patient, the effect is the same as consuming fructose.

(Usually the baby is asymptomatic during the first weeks of life, until he/she consumes fructose (in fruit juices) or milk sweetened with sucrose)

 

Extended answer:

 

Sucrose is formed by glucose linked by an alpha-1, beta-2 O-glycoside linkage to fructose.  Sucrose is hydrolyzed by the action of Sucrase, a disaccharidase of the epithelial brush border, to free glucose and fructose. These monosaccharides are absorbed in the small intestine and travel to the portal system up to the liver.

 

In the liver, glucose is phosphorylated to Glucose 6(P) by Glucokinase (present in the liver) or the Hexokinase (present in the liver and in most of the tissues). (See Kinases enzymes).

 

Fructose also needs to be phosphorylated to be metabolized. This phosphorylation can happens in a reaction catalyzed by Fructokinase, (yielding fructose 1 phosphate), or in a reaction catalyzed by Hexokinase (the specificity over substrate of Hexokinase is relative, so it can catalyzes the phosphorylation of different hexoses).

 

Fructose 6 (P) + ADP <—————-Fructose  + ATP ————-> Fructose 1 (P) + ADP

                                            Hexokinase                                   Fructokinase

 

The Fructose 6 (P) formed by the action of Hexokinase, can be degraded through the glycolysis pathway

 

Fructose 6 (P) + ATP ———————->fructose 1,6 bis (P) + ADP

                                      Phosphofructokinase

 

 

Fructose 1,6 bis (P) <—- ——–> 3 (P) glyceraldehyde + (P) dihydroxyacetone)

                                          Aldolases

 

…until completion.

 

 

The Fructose 1 (P) formed by the action of Fructokinase, will be split by the Aldolase B, aka fructose 1 (P) aldolase, to two trioses,  (just one of them is a phosphorylated triose):

 

Fructose 1 (P) ——————> Glyceraldehyde + (P) dihydroxiacetone

         

 

Errors in Fructose Metabolism:

 

These errors appears usually as a result of the deficit of the enzymes Fructokinase or Aldolase B

 

Fructokinase: Fructose +ATP  ———–> Fructose 1 (P) + ADP

 

Aldolase B: Fructose 1 (P)——> Glyceraldehyde + (P) dihydroxyacetone

 

If the deficitary enzyme is Fructokinase, the patient will present Benign Fructosuria, a disease that usually does not have consequences for the patient and sometimes is discovered by accident when fructose is detected in urine 

 

If the deficitary enzyme is Aldolase B, the disease that appears is Hereditary Fructose Intolerance, an autosomal  recessive disease with a frequency of 1:20 000 newborns.

The lack of this enzyme can produce deleterious consequences, apparently as a result of the trapping of (P) in form of fructose 1 (P) inside the cell, since fructose 1 (P) can not be hydrolyzed to fructose, or isomerized to fructose 6 (P) or glucose 1 (P), or be phosphorylated to Fructose 1,6 bisphosphate.

 

The increase of Fructose 1 (P) in the cell inhibits the action of fructokinase, causing fructosemia.  More dangerous, the decrease of availability of  phosphate inside the cell – since it is trapped as Fructose 1 (P) – causes a decrease in the formation of ATP.  It produces a decline in gluconeogenesis and consequently the patient presents hypoglycemia. It has been described that an important factor in decreasing gluconeogenesis is that aldolase B has also a similar effect to other Aldolases in the catalysis of the interconversion between phosphotrioses and fructose 1, 6 bisphosphate.

The lack of energy in the hepatocytes affects the synthesis of plasma proteins including coagulation factors and the patient can present hemorrhages.

 

Since the production of ATP is impaired, Adenine accumulates and its conversion to Uric acid increases (recall that in the catabolism of purines adenine and Guanine become Uric Acid), and the patient presents Hyperuricemia.

 

So, this patient can present sever hypoglycemia, vomiting, failure to thrive, jaundice, coagulopathy, hepatomegaly, sever metabolic acidosis and the ultimate consequence in a non treated patient is hepatic failure and death.

 

The long term treatment consists basically in the elimination of Fructose and Sucrose from the diet. Since many fruits are rich in fructose, and sucrose and High Fructose Corn Syrup (HFCS) are used for sweeter in the commercial production of many foods, the patient should follow the indications of an experienced nutritionist.

 

For more information about Hereditary Fructose Intolerance:

 

Roths, K.S.: Fructose 1 (P) Aldolase Deficiency (Fructose Intolerance)

  

  

 A good summary about Fructose metabolism can be found at:

The Medical Biochemistry page:  Metabolism of Major Non-glucose Sugars

 

One thought on “A: About a baby with Fructose Intolerance (C-02)

  1. Pingback: About a baby with Fructose Intolerance (C-02) « The Biochemistry Questions Site

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