Vitamin B12 and Folate

1. Vitamin B12
2. Folate
3. Quiz

Vitamin B12 and Folate are two important molecules which are used in the synthesis of DNA. They are both found in the diet and have complex methods of absorption into the body. When these molecules are deficient, megaloblastic anaemia and neurological conditions can occur.

Vitamin B12

Vitamin B12, also known as cobalamin, is a nutrient required for DNA synthesis. It is essential for the formation of reticulocytes and is primarily found in animal origin foods, such as meat, fish, eggs, and cheese, but can also be obtained from fortified foods and supplements. Due to this, vegan diets are prone to deficiencies in B12, therefore vegans are required to take supplements or fortified foods to maintain the normal levels. Fortunately, there are reserves available in the liver that are able to sustain the body for 3 to 5 years, this means that the symptoms of the deficiency won’t present for a long time. Meat eaters have a very large excess in their diet.

Diagram: The absorption pathway of vitamin B12

SimpleMed original by Dr. Tom Bradley

Proteases in the saliva release B12 from protein in meat. To be absorbed, free B12 must bind to haptocorrin (also known as transcobalamin-I), a protein secreted from the salivary glands. This B12-haptocorrin complex passes through the bowel to the small intestine where proteases digest and uncouple it. Following this, the B12 then forms a new complex with a glycoprotein called intrinsic factor, which is secreted from parietal cells in the stomach. This B12-intrinsic factor complex is very important as it binds to receptors in the ileum and then can be internalised by enterocytes. Once inside and released from the intrinsic factor, a new complex with transcobalamin II is formed. This is then released into the bloodstream where it reaches target tissues with the corresponding transporters, notably the liver.

One of the two key reactions which B12 is required for is the methyl group transfer from tetrahydrofolate (see below) to homocysteine. This reaction forms methionine, a component in the synthesis of the DNA base thymidine.

B12 can become deficient in a number of ways:

• Insufficient intake - through a poor or vegan diet.
• Insufficient absorption - this could be due to a number of things:
  
  • Lack of intrinsic factor - this could be due to a gastrectomy (removal of the stomach) or an autoimmune disease resulting in destruction of parietal cells. The latter is known as pernicious anaemia (the most common cause of vitamin B12 deficiency in the UK).
  • Disease of the ileum - Crohn’s disease or an ileal resection reduces absorption of the B12-intrinsic factor complex.
• Insufficient transcobalamin - a congenital deficiency can prevent B12 from entering the target cells. This means there is a deficiency despite there being sufficient B12 present in the body.

Vitamin B12 deficiency is associated with neurological disease and can cause a serious condition called subacute combined degeneration of the cord. This can cause irreversible nervous damage and presents with progressive weakness and numbness in the extremities progressing inwards.