Vitamin B12 Metabolism & Clinical Implications

Question 1

Which are the 2 metabolically active Cobalamins in the body?

Answer 1

Methyl cobalamin & Adenosyl cobalamin

Question 2

Most stable cobalamin form in the body ?

Answer 2

Cyanocobalamin

Question 3

Main storage form of Vitamin B12 in humans ?

Answer 3

Adenosyl cobalamin

Question 4

Absorption of B12 in the terminal ileum is mainly mediated by ?

Answer 4

Intrinsic factor - a glycoprotein synthesized by gastric parietal cells.

Question 5

What is the metabolic significance of Vitamin B12?

Answer 5

• Cofactor in the methylation reaction of Homocysteine to Methionine ( in form of Methyl cobalamin).
  — Enzyme - Methionine synthase
• Cofactor in the conversion of L- Methyl malonyl CoA to Succinyl CoA ( in the form of Adenosyl cobalamin)
  — Enzyme - Methyl malonyl CoA mutase

Question 6

Outline the major causes of Vitamin B12 deficiency in humans.

Answer 6

1. Decreased intake e.g in complete vegetarianism.
2. Impaired B12 absorption
   * Gastric causes e.g pernicious anaemia, gastrectomy, caustic injury
   * Intestinal causes e.g ileal resection, diseases e.g sprue, blind-loop syndrome, D.latum infections
   * Pancreatic insufficiencies
3. Familial selective B12 absorption defects
4. Some medication e.g Colchicine, Neomycin, Omeprazole, ethanol

Question 7

Cardinal signs of Zollinger- Ellison Syndrome ?

Answer 7

• Severe peptic ulcer disease
• Gastro- esophageal reflux disease
• Chronic diarrhea
  — generally affects B12 absorption and may result in deficiencies.

Question 8

What are the major signs of Vitamin B12 deficiency in humans?

Answer 8

• Atrophic glossitis - shiny tongue
• Shuffling broad gait
• Anemia & related conditions - megaloblastic anaemia
• Vaginal atrophy
• Malabsorption
• Jaundice
• Personality changes
• Hyper homocysteinaemia
• Neurologic symptoms

Question 9

Outline the neurological symptoms associated with Vitamin B12 deficiency.

Answer 9

• Paresthesias
• Memory loss
• Numbness & weakness
• Loss of dexterity due to loss of vibration and position sense
• Symmetric neuropathy
• Severe weakness, spasticity, clonus , paraplegia & incontinence
• Subacute combined degeneration of the dorsal & lateral spinal columns - due to defective myelination

Question 10

Symptoms associated with Vitamin B12 overload?

Answer 10

• Liver diseases
• Myeloid blood malignancies
• Chronic renal failure
• Autoimmune or inflammatory diseases
• Gaucher’s disease
• Solid tumours