Intrinsic Factor Explained: Role, Deficiency & Solutions

Intrinsic factor is a glycoprotein secreted by the gastric mucosa's parietal (human) or chief (rodent) cells. It is important in the absorption of vitamin B₁₂ (cobalamin) in the intestine in humans, and failure to produce or utilise intrinsic factor results in the condition pernicious anaemia.

The action of pepsin and acid in the stomach releases dietary vitamin B₁₂ from ingested proteins. It is quickly bound by one of two vitamin B₁₂-binding proteins found in the gastric juice present; at low pH, these binding proteins have a higher affinity for the vitamin than intrinsic factor. Pancreatic proteases digest the binding proteins in the small intestine, releasing vitamin B₁₂, which then binds to intrinsic factor. Finally, intrinsic factor receptors on the ileal mucosa bind the complex, allowing vitamin B₁₂ to be absorbed into portal blood.

Vitamin B₁₂ is required for the maturation of erythrocytes in all mammals, and a lack of this vitamin results in anaemia. Because efficient vitamin B₁₂ absorption in humans is dependent on intrinsic factor, diseases that reduce intrinsic factor secretion (e.g., atrophic gastritis), interfere with cleavage of the binding proteins (e.g., pancreatic exocrine insufficiency), or decrease binding and absorption of the intrinsic factor-vitamin B₁₂ complex (e.g., ileal disease or resection) can result in this type of anaemia. A lack of cobalt, a necessary component of vitamin B₁₂, can cause anaemia in cattle and sheep, among other symptoms of disease.

What is the Function of Castle Intrinsic Factor?

The other name for Intrinsic factor (IF) is a gastric intrinsic factor (GIF), which is a glycoprotein produced by the parietal cells of the stomach. It is essential for the absorption of vitamin B₁₂ later on in the ileum of the small intestine.

Intrinsic Factor Structure

The intrinsic factor found in gastric juice is extremely specific for genuine Cbl. Intrinsic factor has two binding sites: one for Cbl and one for the ileal cubilin receptor. The glycoprotein is composed of a 30 kDa N-terminal peptide fragment (alpha domain) and a 20 kDa C-terminal glycopeptide fragment (beta domain), which are joined by a protease-sensitive linker. The beta domain must form a hydrogen bond with the lower ligand (DMB) in Cbl. Conformational changes later cause the Cbl molecule to become sandwiched between the two domains.

Tests for Intrinsic Factor Insufficiency

Anti-intrinsic factor antibody is a type of anti-intrinsic factor antibody (Specific to pernicious anemia).

Antibody against parietal cells. If the antibodies are negative, the Schilling test is performed to aid in Cbl uptake. Done by injecting free Cbl intramuscularly and taking radiolabeled Cbl orally; if the intrinsic factor is sufficient and there is no problem with its function, the urine will show the radiolabeled Cbl; otherwise, it will not.

Intrinsic Factor Deficiency

Intrinsic factor deficiency prevents the body from using vitamin B₁₂ efficiently or at all, regardless of B₁₂ levels. Oral cobalamin supplementation will have little effect in this case. The only known and effective treatment for IF deficiency is intramuscular or intravenous hydroxocobalamin injection. This molecule enters the liver after bypassing the intestine and skipping the haptocorrin and intrinsic factor binding steps.

The intrinsic factor antibody can reduce or stop intrinsic factor production. The intrinsic factor antibody prevents intrinsic factor from binding to cobalamin or prevents cells from absorbing the IF-Cbl complex.

Information in our DNA on chromosome number 11 – more specifically, at chromosome location – controls gene expression for intrinsic factor synthesis. If both chromosome alleles of this GIF gene are damaged, less or no intrinsic factor is produced.

There are two types of intrinsic factor antibody tests that can be performed:

Type 1)  intrinsic factor blocking antibody

Type 2 ) intrinsic factor blocking antibody (also called precipitating antibody type 2)

B₁₂ is prevented from binding to IF in the ileum by a type one IF blocking antibody. This type of IF deficiency is responsible for the majority of cases of pernicious anaemia.

Treatment

In most countries, intramuscular vitamin B₁₂ injections are used to treat pernicious anaemia. Vitamin B₁₂ is absorbed orally without intrinsic factor, but at a much lower rate than when an intrinsic factor is present. Despite the low absorption rates, oral vitamin B₁₂ therapy is effective in alleviating the symptoms of pernicious anaemia. Although there is no evidence that sublingual vitamin B₁₂ administration is superior to oral administration, only Canada and Sweden routinely prescribe this route of administration.

Mechanism of Action of Intrinsic Factor

Intrinsic factor (IF), also known as a gastric intrinsic factor (GIF), is a glycoprotein produced by the stomach's parietal cells that are required for vitamin B₁₂ (cobalamin) absorption later in the small intestine. When vitamin B₁₂ is combined with the intrinsic factor, the intrinsic factor reduces protease degradation as well as increases vitamin B₁₂ absorption.

Intrinsic Factor in Stomach

Intrinsic factor is a glycoprotein secreted by the gastric mucosa's parietal (human) or chief (rodent) cells. It is important in the absorption of vitamin B₁₂ (cobalamin) in the intestine in humans, and failure to produce or utilise intrinsic factor results in the condition pernicious anaemia.