Vitamin B12 absorption

Question 1

Vitamins

Answer 1

Water soluble: B, C
Fat soluble: A, D E K

Question 2

Vitamin B12

Answer 2

Cobalamin
Meat, fish, diary
RDA 1-2.5 mg daily

Question 3

Types of absorption of Vitamin B12

Answer 3

Passive
-Buccal, duodenal, ileal mucosa
-Rapid, extremely inefficient
- <1% oral dose absorbed

Active transport
-Ileum
-Gastric intrinsic factor mediated
- 70% ingested amount absorbed

Question 4

Absorption of vitamin B12

Answer 4

Released from food and bound to haptocorrin (transcobalamin 1)

Haptocorrin produced by salivary gland

Intrinsic factor (glycoprotein) secreted by parietal cell

At duodenal haptocorrin degraded releasing V B12

V B12 captured by intrinsic factor

At terminal ileum endocytosed by cubam

Inside enterocyte degraded intrinsic factor releases V B12

ABC transporter releases V B12 into blood

V B12 binds to transcobalamin 2

Question 5

Transcobalamin 2

Answer 5

Important for cellular uptake

Question 6

Excess Vitamin B12

Answer 6

Sent to liver for storage

Question 7

Cellular role of Vitamin B12

Answer 7

Homocysteine > Methionine
5 methyl TH folate > TH folate
methymalonyl-CoA > Succinyl-CoA

Question 8

Intrinsic factor in absorption

Answer 8

Produced in parietal cell
Absence = pernicious anaemia

Question 9

Pernicious anaemia

Answer 9

Autoimmune atrophic gastritis
Destruction of gastric parietal cells
Directed against proton pump
Causes achlorhydria

Question 10

Vitamin B12 deficiency

Answer 10

Dietary
Loss of gastric parietal cells/intrinsic factor
Intestinal bacterial overgrowth
Ileal mucosa disorder
Plasma transport disorder

Question 11

Drug induced Vitamin B12 deficiency

Answer 11

PPI (acid)
H2 antagonists (acid)
Oral contraceptives (transcobalamin)
Hormone replacement therapy (transcobalamin)
Metformin (B12 absorption)
Chlorchicine (ileum mucosa inhibitors)

Question 12

Consequence of vitamin B12 deficiency

Answer 12

Neurological
-Paresthesia
-Sensory loss
-Gait ataxia
-Weakness in legs

CNS
Subacute combined degeneration
Digestive
-Hunter’s glossitis

Cardiovascular
-Angina
-Venous thromboembolic disease

Gynaecology
-Infertility

Question 13

Active forms of vitamins

Answer 13

Deoxyadensosylcobalamin
Methylcobalamin

Question 14

Treatment of vitamin B12 deficiency

Answer 14

Oral
-Cyanocobalamin

Parenteral (severe)
-Hydroxycobalamin

Question 15

Vitamin B9

Answer 15

Folate, folic acid
Dark green vegetables
Fruits and fruit juice
Meat, seafood, poultry, eggs
Fortified cereals, bread
200 mg daily
400mg daily in pregnancy

Question 16

Folate chemistry

Answer 16

Conjugated to polyglutamyl chain
Absorbed in monoglutamate form
Hydrolysed by folylpoly-γ-glutamate carboxypeptidase
Main dietary 5-MTHF

Question 17

Absorption of folate

Answer 17

Occurs in duodenal and jejunum
From lumen by proton-coupled folate transporter PCFT
From reduced folate carrier RFC
Folate exchanged for organic phosphate OP

Folate reduced to 5-MTHF
Both exported from enterocyte by organic anion transporter OAT

Question 18

Cellular role of folate

Answer 18

Transported as mono-glutamyl derivative
Some bound to albumin
Plasma concentration 10-30nmol/L

Essential for methyl transfers to amino acids, nucleotides, biomolecules

Question 19

Folate deficiency

Answer 19

Dietary
PCFT issues
Intestinal disease: coeliac, IBD
Chronic alcohol use
Pregnancy

Question 20

Drug induced folate deficiency

Answer 20

Cholestyramine
Sulfasalazine
Trimethoprim
Methotrexate
Metformin

Question 21

Folate deficiency symptoms

Answer 21

Sore tongue
GI symptoms
Neurological
Megaloblastic anaemia

Question 22

Folate deficiency treatment

Answer 22

Oral folic acid 1-4 months