Vitamin B12 (Cobalamin) Flashcards
B12 is water soluble
True
Vitamin B12 is only synthesized by?
Bacteria
Where is vitamin B12 (cobalamin) found?
Found only in animal products (meat, fish, poultry, dairy products) and is not affected by cooking.
Recommended daily dose of vitamin B12?
2 mcg/day
Total body store of vitamin B12?
2-5 mg (3 year’s worth)
How is vitamin B12 transported in blood plasma?
- 20% bound to transcobalamin 2 (TC II) = active form (holotranscobalamin) that is made in the GIT cells (enterocytes) - 80% bound to transcobalamin 1 and 3 with no known roles in B12 metabolism
Holotranscobalamin
Active form of B12, that is made in the GIT cells (enterocytes)
Transcobalamin 1 = haptocorrin (=R protein)
Produced by salivary glands and serves to protect cobalamin (vitamin B12) from acid degradation in stomach by producing haptocorrin-B12 complex.
Describe process of B12 absorption
1) B12 (cobalamin) comes into the stomach bound to food and gets cleaved in the acid environment and becomes bound to the R protein (haptocorrin) which protects the vitamin B12 from being destroyed.
2) It then moves to the small intestine, where more enzymes comes from the pancreas. The alkaline environment here destroys the R protein and the B12 gets bound the by the intrinsic factor (IF).
3) Intrinsic factor produced in stomach by parietal cells.
4) Intrinsic factor carries the vitamin B12 until the distal ileum where it is absorbed into the blood stream. This occurs via intrinsic factor receptors (Called cubam)
5) It moves across these cells of the distal ileum, and is then transported to be bound by transcobalamin 2.
6) The complex of B12 is then bound by transcobalamin, where it then moves to the rest of the body.
Vitamin B12 is an essential coenzyme for?
1) Methionine synthase (MS) which has a role in DNA synthesis: Homocysteine -> Methionine
2) Methylmalonyl CoA mutase (MCM) metabolism of fatty acids and some amino acids; energy production (citric acid/Kreb’s cycle): Methylmalonic acid -> Succinyl CoA
Methionine synthase (MS) has a role in?
DNA synthesis
Methionine synthase converts _____ into Methionine.
Homocysteine
Methylmalonyl CoA mutase (MCM) metabolism converts _____ to ______.
Methylmalonic acid -> Succinyl CoA
B12 deficiency results in:
- Increased homocysteine levels
- Reduced methionine levels
- Reduced formation of THF (tetrahydrofolate): also caused by folate deficiency
Reduced formation of Tetrahydrofolate is also caused by ?
Folate deficiency
Reduced formation of tetrahydrofolate (THF) causes what?
Causes impaired DNA synthesis, affecting all rapidly growing tissues (BM - megaloblastic anaemia, Epithelial surfaces - GIT symptoms, Foetus - neural tube defects).
List causes of vitamin B12 deficiency
- Inadequate intake
- Digestion and absorption problems
- Inadequate release of B12 from food due to absent/reduced enzymes and/or acid i.e. gastrectomy, chronic atrophic gastritis/achlorhydria, H. pylori; drugs (e.g. H2 antagonists, proton pump inhibitors)
- Inadequate production of functional intrinsic factor
- Terminal ileal disease
- Competition for intestinal B12
- Transport abnormalities
Inadequate production of functional intrinsic factor causes?
Pernicious anaemia, an autoimmune disease that attacks gastric parietal cells that produce the intrinsic factor.
Inadequate production of functional intrinsic factor (pernicious anaemia) is associated with?
It is associated with other organ specific autoimmune disorders (e.g. hypoparathyroidism, Addison’s disease, thyroid disease)
Terminal ileal disease include?
Coeliac disease, ileal resection, Crohn’s disease, hereditary reduced uptake of IF-Cbl.
Competition for intestinal B12 is caused by?
Bacterial overgrowth/tapeworm in the small bowel
Transport abnormalities that cause vitamin B12 deficiency include deficiency of?
Transcobalamin
Clinical manifestations of vitamin B12 deficiency include?
- Can be asymptomatic
- Epithelial regeneration causes glossitis and stomatitis
- The GI symptoms can be anorexia, weight loss, constipation
- Mild jaundice
- Bruising due to platelets, or infections due to white cell impacts
- Subacute combined degeneration of the cord due to demyelination
Clinical manifestation: subacute combined degeneration of the spinal cord due to demyelination can present due to?
- Combination of peripheral sensory nerves and the posterior and lateral columns of spinal cord affecting proprioception/vibration and lateral corticospinal tracts mediating motor function (LL>UL)
- Optic nerve atrophy and CNS disease with cognitive disturbances
Haematological blood results of B12 deficiency
Low Hb (haemoglobin levels.
MCV: 110-130 fL, ineffective erythropoiesis, raised bilirubin, LDH (lactate dehydrogenase)
Lab result of holotranscobalamin measures?
Measures only B12 bound to transcobalamin 2 (TC2 = holotranscobalamin) with a normal range: >35 pmol/L
Blood film lab result of vitamin B12 deficiency shows?
Oval macrocytes, anisocytosis (difference in size)/ poikilocytosis (difference in shape), hypersegmented neutrophils (> 5 lobes), WCC and platelets mostly normal but they may be low (pancytopenia is low Hb, WBC and platelets low)
Bone marrow lab result of vitamin B12 deficiency will show?
Hypercellular: more cells than normal because the body is signalling it is anaemic, but these cells are not normal.
Erythryoblasts (RBC precursor) have nuclear irregularity, increased nucleus: cytoplasm ratio due to delayed nuclear maturation relative to that of the cytoplasm (which is based on protein not DNA production), and are macrocytic.
Auto-haemolysis because they are dysfunctional, i.e. they die, and this creates raised bilirubin (by-product of Hb metabolism) and lactate dehydrogenase (cause of cell destruction and can cause a raised LDH).
Dysplastic megakaryocytes (giant)
