What is the major function of haptoglobin (a protein that binds hemoglobin)?

The Major Function of Haptoglobin

The major function of haptoglobin is to bind hemoglobin and prevent the loss of iron, making option C the correct answer.

Haptoglobin's Primary Role

Haptoglobin is a plasma glycoprotein that serves as the primary hemoglobin-binding protein in the circulation. When intravascular hemolysis occurs, hemoglobin is released into the bloodstream. Free hemoglobin is potentially harmful for two main reasons:

1. It can cause kidney damage through filtration in the glomeruli
2. It contains iron that could be lost from the body

Haptoglobin prevents these negative outcomes by:

• Binding free hemoglobin with high affinity
• Creating haptoglobin-hemoglobin complexes that are too large to be filtered by the kidneys
• Directing these complexes to be cleared by the reticuloendothelial system, particularly by macrophages in the liver
• Preserving the iron within hemoglobin for recycling and preventing its loss

Mechanism of Action

The haptoglobin-hemoglobin complex is recognized by the CD163 receptor on macrophages, which then internalize the complex. Inside the macrophage:

• The complex is degraded in lysosomes
• The iron from heme is recovered
• The iron is either stored as ferritin or released back into circulation bound to transferrin
• This process prevents iron loss that would otherwise occur if free hemoglobin were filtered by the kidneys 1

Additional Functions of Haptoglobin

While binding hemoglobin and preventing iron loss is the primary function, haptoglobin also:

• Acts as an antioxidant by preventing hemoglobin-induced oxidative tissue damage 1, 2
• Functions as a positive acute phase protein that increases during inflammation
• Has immunomodulatory effects, including suppression of lymphocyte function 1
• May play a role in angiogenesis 3

Haptoglobin Polymorphism and Clinical Significance

Haptoglobin exists in three major phenotypes (Hp 1-1, Hp 2-1, and Hp 2-2), which differ in their ability to bind hemoglobin:

• Hp 1-1 is biologically the most effective at binding free hemoglobin
• Hp 2-2 is the least active
• Hp 2-1 has intermediate activity 1

These phenotypic differences have clinical implications, particularly in conditions involving hemolysis or oxidative stress. For example, the Hp 2-2 genotype has been associated with increased risk of vascular complications in patients with diabetes, likely due to decreased antioxidant capability and less efficient clearance of hemoglobin-haptoglobin complexes 2, 4.

Why Other Options Are Incorrect

A. Attaching to bilirubin - This is incorrect as haptoglobin does not bind to bilirubin. Bilirubin is bound primarily by albumin in circulation.

B. Maintaining proper oxygen levels - While hemoglobin carries oxygen, haptoglobin's role is not to maintain oxygen levels but rather to bind free hemoglobin.

D. Inhibiting breakdown of renal tubules - While haptoglobin indirectly protects the kidneys by preventing hemoglobinuria, this is a secondary effect of its primary function of binding hemoglobin and preserving iron.