B vitamins & Folate

Question 1

How is vitamin B12 (Cobalamin) made and where can you find it?

Answer 1

Synthesised exclusively by microorganisms. Found in liver and kidneys.

Question 2

Why do we need vitamin B12?

Answer 2

• Maintain the normal function of the brain and nervous system.
• Involved in the formation of RBCs
• Involved in metabolism of all cells
• Key role in DNA synthesis and regulation.

Question 3

What does vit B12 use for absorption and transport and where is it made?

Answer 3

Intrinsic factors. Made in gastric parietal cells.

Question 4

Absorption process of vit B12 to the circulation.

Answer 4

• B12 binds to IF
• The B12/IF complex moves to the ileum
• They bind to a receptor called cubilin on the enterocyte
• B12 is absorbed and released into circulation.
• IF is destroyed
• Once inside, B12 binds to TC2 which acts as a plasma transporter.
• The complex is bound to a receptor and is endocytosed.
• One inside TC2 is degraded in the lysosome and vit B12 is released.

Question 5

What is the biochemical function of Vitamin B9?

Answer 5

It is a co-factor for the conversion of succinyl coA and glycine into ALA by ALA synthase.

Question 6

How is vit B9 absorbed?

Answer 6

Passive absorption in the jejunum and ileum.

Question 7

What is the RDA of vit B9?

Answer 7

1.5-2.0mg

Question 8

What is the metabolic function of vit B12?

Answer 8

• Co-factor in the conversion of methylmalonyl-coA to Succinyl-coA.
• Co-factor for the conversion of homocysteine to methionine.

Question 9

How much vit B12 do we need to absorb daily?

Answer 9

To maintain body stores: 1-3ug

To maintain health: 0.5ug

Question 10

Where is vit B12 stored and how is it lost?

Answer 10

Stored in the liver.

Lost via urine and faeces.

Question 11

Sources of folate.

Answer 11

• Leafy green vegetables
• Liver and liver products
• Fortified breakfast cereals

Question 12

Why do we need folate?

Answer 12

• Synthesis of purine/pyrimidine precursors of DNA.
• Important during periods of rapid division and growth: pregnancy/infancy.
• Production of healthy RBCs.
• Needed for development of the neural tube.

Question 13

How is Folic acid activated, absorbed and transported?

Answer 13

• Folic acid needs to be reduced to tetrahydrofolate (THF).
• Absorption takes place in duodenum and jejunum.
• Absorbed folates are converted into 5-MTHF monoglutamate before entering the portal blood system.
• Plasma folate circulates bound or unbound to plasma proteins.
• Vit B12 is needed to convert methyl THF to THF

Question 14

What are the causes of Vit B12 deficiency?

Answer 14

• Pernicious anaemia: impairs absorption of vit B12 as a consequence of a reduction in IF.
• Veganism: no vit B12 in plants.

Question 15

What are the causes of folate deficiency?

Answer 15

• Poor dietary habits: alcoholics
• Impaired absorption, metabolism or increased demand for the vitamin.
• Anticonvulsants and oral contraceptives.

Question 16

Consequences of folate and vit B12 deficiency.

Answer 16

• Closure of the neural tube around the 28th day of pregnancy.
• Neural tube defects: Anencephaly
• Neurological complications

Question 17

What are the clinical features of folate and vit B12 deficiency?

Answer 17

• Mild jaundice
• Neuropathy
• Tingling in feet and difficulty in gait
• Glossitis

Question 18

Haematological disorders due to folate and vit B12 deficiency?

Answer 18

Folate: megaloblastic anaemia

Vit B12: Pernicious anaemia (form of megaloblastic anaemia)

Question 19

What is megaboblastic anaemia and why does it occur?

Answer 19

• Inhibition of DNA production during erythropoiesis
• Erythroblasts in the bone marrow show maturation of the nucleus being delayed relative to the cytoplasm.
• So, we have Megablasts in the bone marrow and large RBCs in the blood because DNA synthesis and division is delayed.

Question 20

Haematological features of Megaloblastic anaemia.

Answer 20

• Macrocytosis
• Increased MCV >90fl
• Oval macrocytes
• Increased lobe number (>5) in neutrophils
• Low reticulocyte count
• WBC and platelet count reduced.
• Serum folate <3ug/L

Question 21

What is pernicious anaemia?

Answer 21

Megaloblastic anaemia caused by lack of IF.

Question 22

What happens in pernicious anaemia?

Answer 22

• Autoimmune attack on the gastric mucosa so the stomach wall becomes thin and secretion of acid and IF are reduced.
• Antibodies against gastric parietal cells are found in 85% of patients.
• Serum gastrin levels are raised.

Question 23

What are the tests and treatment for pernicious anaemia?

Answer 23

• Test for methylmalonyl coA
• Intramuscular injection of vit B12
• Vit B12 <200pg/mL

Question 24

How do you treat megaloblastic anaemia caused by folate deficiency?

Answer 24

• Oral dose of folic acid

- Vit B12 deficiency must be ruled out before treating with folate.