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A 7-month-old baby girl, the second child born to unrelated parents was brought to Pediatrics outdoor department. History revealed that she did not respond well to breast-feeding and was changed entirely to a formula based on cow’s milk at 4 weeks. Between 7 and 12 weeks of age, she was admitted to the hospital twice with a history of screaming after feeding, but was discharged after observation without a specific diagnosis. Elimination of cow’s milk from her diet did not relieve her symptoms; her mother reported that the screaming bouts were worse after the child drank juice and that she frequently had gas and a distended abdomen. The child was diagnosed having ‘Hereditary fructose intolerance’. The mother of the child was instructed to eliminate fructose containing foods from the child’s diet and was strictly instructed to feed milk without table sugar. The table sugar (sucrose), a disaccharide, contains glucose and fructose linked as:

A. O-α-D-glucopyranosyl-(1->6)-α -D- fructofuranoside

B. O-β-D-glucopyranosyl-(1->6)-α -D- fructofuranoside

C. O-α-D-glucopyranosyl-(1->2)-β -D-fructofuranoside

D. O-α-D-glucopyranosyl-(1->2)-α -D-fructofuranoside

E. None of the above.

The correct answer is C- O-α D-glucopyranosyl-(1->2)-β -D-fructofuranoside. The onset of symptoms after ingestion of juice (fructose or fructose containing diet) is a sign of hereditary fructose Intolerance’.

Hereditary fructose intolerance is caused by deficiency of Aldolase B, the enzyme required for the metabolism of fructose. These patients are healthy and asymptomatic until fructose or sucrose (table sugar) is ingested (usually from fruit, sweetened cereal, or sucrose-containing formula). Elimination of dietary fructose is both a compulsory and therapeutic step.

In patients who are ill, elimination may also serve as a diagnostic test because all symptoms should completely resolve. With this treatment, as the patient matures, symptoms become milder, even after fructose ingestion, and the long-term prognosis is good.

Table sugar (sucrose) is a source of fructose and in Sucrose, the anomeric carbon atoms of a glucose unit and a fructose unit are joined; the configuration of this glycosidic linkage is α-for glucose and β-for fructose (figure).


Structure of sucrose

Figure- Structure of sucrose

Sucrose can be cleaved into its component monosaccharides by the enzyme sucrase.

An overview of properties of sucrose

  • Sucrose has no free reactive group because the anomeric carbons of both monosaccharides units are involved in the glycosidic bond. Therefore, sucrose neither shows reducing nor mutarotation characters.
  • Sucrose is called invert sugar because the optical activity of sucrose (dextrorotatory) is inverted after hydrolysis (by an acid or an enzyme (invertase or sucrase) into an equimolar mixture of its two components glucose (+52.5) and fructose (-92.5) and the optical activity of the mixture becomes levorotatory.  




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Case Details

A 54 –year- old woman who was bed bound in a nursing home began to develop swelling of her left leg. She was evaluated with venous Doppler ultrasound and was found to have a deep vein thrombosis. She was immediately started on heparin to prevent the clot from further enlarging.

What is the chemical nature of Heparin?

How will it help in preventing the clot formation?

Case discussion


Heparin also called α Heparin, is a highly sulfated GAG(Glycosaminoglycans). It is an anticoagulant widely used in clinical practice. It is present in liver, lungs, spleen and monocytes. Commercial preparations are from animal lung tissues. It contains repeating units of sulfated Glucosamine and either of the two uronic acids-D-Glucuronic acid and L-Iduronic acid. In fully formed Heparin molecules 90% or more of uronic acid residues are L-Iduronic acid. It is strongly acidic due to sulphuric acid groups and readily forms salts.

Clinical role of Heparin

In vitro Heparin is used as an anticoagulant while taking blood samples, 2 mg/10 ml of blood is used. It is considered the most satisfactory anti coagulant as it does not produce a change in red cell volume or interfere with subsequent determinations.

In vivo Heparin is used in suspected thromboembolic conditions to prevent intravascular coagulation. Heparin is used for anticoagulation for the following conditions:

  • Acute coronary syndrome,
  • Atrial fibrillation
  • Deep-vein thrombosis and pulmonary embolism.
  • Cardiopulmonary bypass for heart surgery.

Mechanism of action

Role of heparin as an anti-coagulant

It produces its major anticoagulant effect by inactivating thrombin and activated factor X (factor Xa) through an antithrombin (AT) dependent mechanism. Heparin binds to AT through a high-affinity pentasaccharide. (See figure-1)


Figure-1-showing the binding of heparin to antithrombin. To potentiate thrombin inhibition, heparin must simultaneously bind to antithrombin and thrombin.


Binding of Heparin to lysine residues in antithrombin produces conformational changes which promote the binding of the latter to serine protease “thrombin” which is inhibited, thus fibrinogen is not converted to fibrin and the coagulation is inhibited.(See figure -2)

Figure-2-showing the mechanism of action of Heparin. Heparin has a multitude of effects on the clotting cascade; however, the primary sites of action are the inhibition of factor II, also called thrombin, and factor X.
Role of Heparin as a coenzyme

Heparin acts in the body to potentiate the activity of the enzyme “Lipoprotein lipase”. Heparin binds specifically to the enzyme present in capillary walls causing its release in to the circulation. Hence it is also called “releasing factor”.

Administration of Heparin

Heparin is given parenterally, as it is degraded when taken by mouth. It can be injected intravenously or subcutaneously. Intramuscular injections are avoided because of the potential for forming hematomas.

Because of its short biologic half-life of approximately one hour, heparin must be given frequently or as a continuous infusion. However, the use of low-molecular-weight heparin (LMWH) has allowed once-daily dosing, thus not requiring a continuous infusion of the drug. If long-term anticoagulation is required, heparin is often used only to commence anticoagulation therapy until the oral anticoagulant Warfarin takes effect.

Adverse effects

The most common side effect is bleeding .The risk of bleeding increases with higher dosage.

A serious side-effect of heparin is heparin-induced thrombocytopenia (HIT). HIT is caused by an immunological reaction that makes platelets a target of immunological response, resulting in the degradation of platelets. This is what causes thrombocytopenia. This condition is usually reversed on discontinuation, and can generally be avoided with the use of synthetic heparins. There is also a benign form of thrombocytopenia associated with early heparin use, which resolves without stopping heparin.

There are two nonhemorrhagic side-effects of heparin treatment. The first is elevation of serum Aminotransferases levels, which has been reported in as many as 80% of patients receiving heparin. This abnormality is not associated with liver dysfunction, and it disappears after the drug is discontinued. The other complication is hyperkalemia, which occurs in 5 to10% of patients receiving heparin, and is the result of heparin-induced aldosterone suppression. The hyperkalemia can appear within a few days after the onset of heparin therapy.

Osteoporosis  – has also been reported with long-term Heparin therapy, since Heparin causes bone loss both by decreasing bone formation and by enhancing bone resorption.

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