vit B12

Question 1

Mention the sources and RDA of Cobalamin

Answer 1

1. Naturally found in animal food products like liver, meat, fish, egg and dair product. Curd is also a good source because lactobacillus can synthesise B12.
2. Fortified cereals (Containing added vitamins and minerals)

RDA ⇒ 1-2 ug/day.

Question 2

Describe, with a diagram, the absorption, transport and storage of Cobalamin

Answer 2

Absorption:
1. B12 is ingested and the HCL in the stomach separates B12 from the food that its attached to
2. The free B12 then binds to a R-protein (Haptocorrin, secreted by the salivary glands) and the complex moves into the intestine.
3. In the intestine, the B12 is released from the R-protein by a pancreatic enzyme
4. B12 then binds to intrinsic factor and the complex is absorbed at the terminal ileum

Transport:
1. Transported in the blood by specific binding proteins (transcobalamin)

Storage:
1. Stored in the liver (2-5mg)

Question 3

List the coenzyme forms and functions of cobalamin

Answer 3

Biological active form (coenzyme forms) of B12 are methylcobalamin and deoxyadenosylcobalamin

Functions:
1. Remethylation of Homocysteine to methionine
- Methylcobalamin is the cofactor for methionine synthase.
- Uses N5-methyl THF as the methyl donor (Comes from folic acid, B11)

2. Isomerization of methylmalonyl CoA to Succinyl CoA
   - Deoxyadenosylcobalamin is a cofactor for methylmalonyl CoA mutase
   - makes succinyl CoA

Question 4

Explain the causes of Cobalamin, B12, deficiency disorders

Answer 4

1. Pernicious anemia
   → Results of autoimmune destruction of parietal cells. Therefore, cannot produce intrinsic factor
   → Lack of intrisic factor disallows the absorption of B12
   → B12 deficiency
2. Decrease in absorption
   → Absorptive surface is reduced by gastrectomy, resection of ileum, and malabsorption syndromes (celiac’s disease).
   → Think of this as a physical / mehcanical change to absorptive environment + celiac
3. Nutritional B12 deficiency:
   → Rare, but may occur among strict vegetarians

Question 5

Explain how B12 deficiency ledas to folic acid deficiency (Folate trap hypothesis)

Answer 5

1. B12 deficiency → blocks the conversion of N5-methyl THF to TF
2. Folate is trapped as N5-methyl THF → Folic acid deficiency

Question 6

Construct the link b/w B12 deficiency and its hematologic and neurologic manifestations

Answer 6

Hematologic manifestations:
1. B12 deficiency → Folate trap hypothesis → Folate deficiency → Megaloblastic anaemia
- Megaloblastic anemia is characterized by large RBC called megaloblasts in the bone marrow
- Hypersegmented neutrophils are also seen

Neurological manifestations:
- Often considered to be late manifestations of anemia.
- Can arise in patients with pernicious anemia
- Blocked producion of succinyl CoA, and therefore accumulation of methylmalonyl CoA. Accumulation of mmCoA → impaired fatty acid synthesis → demyelination → slows nerve impulse
- Excess methylmalonyl CoA is excreted in urin as methylmalonic acid
- Symptoms of dizziness, depression, pale skin, sore tongue etc.

Treatments:
1. Folic acid alone should not be given in megaloblastic anemia (can aggravate the neurological manifestations of b12 deficiency)
2. Folic acid and B12 must be given in combination