Vitamin B12 absorption Flashcards
Vitamins
Water soluble: B, C
Fat soluble: A, D E K
Vitamin B12
Cobalamin
Meat, fish, diary
RDA 1-2.5 mg daily
Types of absorption of Vitamin B12
Passive
-Buccal, duodenal, ileal mucosa
-Rapid, extremely inefficient
- <1% oral dose absorbed
Active transport
-Ileum
-Gastric intrinsic factor mediated
- 70% ingested amount absorbed
Absorption of vitamin B12
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
Transcobalamin 2
Important for cellular uptake
Excess Vitamin B12
Sent to liver for storage
Cellular role of Vitamin B12
Homocysteine > Methionine
5 methyl TH folate > TH folate
methymalonyl-CoA > Succinyl-CoA
Intrinsic factor in absorption
Produced in parietal cell
Absence = pernicious anaemia
Pernicious anaemia
Autoimmune atrophic gastritis
Destruction of gastric parietal cells
Directed against proton pump
Causes achlorhydria
Vitamin B12 deficiency
Dietary
Loss of gastric parietal cells/intrinsic factor
Intestinal bacterial overgrowth
Ileal mucosa disorder
Plasma transport disorder
Drug induced Vitamin B12 deficiency
PPI (acid)
H2 antagonists (acid)
Oral contraceptives (transcobalamin)
Hormone replacement therapy (transcobalamin)
Metformin (B12 absorption)
Chlorchicine (ileum mucosa inhibitors)
Consequence of vitamin B12 deficiency
Neurological
-Paresthesia
-Sensory loss
-Gait ataxia
-Weakness in legs
CNS
Subacute combined degeneration
Digestive
-Hunter’s glossitis
Cardiovascular
-Angina
-Venous thromboembolic disease
Gynaecology
-Infertility
Active forms of vitamins
Deoxyadensosylcobalamin
Methylcobalamin
Treatment of vitamin B12 deficiency
Oral
-Cyanocobalamin
Parenteral (severe)
-Hydroxycobalamin
Vitamin B9
Folate, folic acid
Dark green vegetables
Fruits and fruit juice
Meat, seafood, poultry, eggs
Fortified cereals, bread
200 mg daily
400mg daily in pregnancy
Folate chemistry
Conjugated to polyglutamyl chain
Absorbed in monoglutamate form
Hydrolysed by folylpoly-γ-glutamate carboxypeptidase
Main dietary 5-MTHF
Absorption of folate
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
Cellular role of folate
Transported as mono-glutamyl derivative
Some bound to albumin
Plasma concentration 10-30nmol/L
Essential for methyl transfers to amino acids, nucleotides, biomolecules
Folate deficiency
Dietary
PCFT issues
Intestinal disease: coeliac, IBD
Chronic alcohol use
Pregnancy
Drug induced folate deficiency
Cholestyramine
Sulfasalazine
Trimethoprim
Methotrexate
Metformin
Folate deficiency symptoms
Sore tongue
GI symptoms
Neurological
Megaloblastic anaemia
Folate deficiency treatment
Oral folic acid 1-4 months
