L6 B12, B9 metabolism and anaemias

key role of vitamin b12

• maintaining normal function of brain and nervous system

• formation of RBC

• dna synthesis and regulation

how much vitamin b12 is needed

1-3 micrograms

0.5 to maintain health

absorption of B12

• intrinsic factor and gastric acid produced by gastric parietal cells

• B12/IF complex moves from stomach to ileum

• binds to receptor on enterocyte then absorbed

• B12 released into circulation

• intrinsic factor is degraded and not recycled

post enterocyte circulation of B12

• transcobalamin binds to B12 in circulation, binds to receptor on surface of target cell

• Once inside the transcobalamin is degraded by lyososomes to release B12

storage and loss of B12

• storage - liver, 3-5mg

• Loss - urine and faces, desquamation of epithelial and excretion in bile, 0.05-0,1% of body content daily

• Takes years for B12 deficiency to occur - takes long time for stores to be depleted

vitamin b6 common where, absorption and daily requirement

pyridoxine, common in fruit cereal meat, passive absorption in jejunum and ileum, daily requirement 1.5-2.0mg

metabolic pathway of B6 and B12 in the mitochondrion 

• propionyl-coA → methylmalonyl-coA

• methylmanoyl-coA → succinyl coA

  • catalysed by mm-mutase and cofactor B12

• succinyl-coA → ALA

  • cofactor B6

• ALA→ Haem

can the body synthesise b9

• no

• found in lentils, kidney beans, broccoli, spinach..

activation absorption and transport of folic acid

• folic acid is reduced to tetrahydrofolate methylTHF by MTHFR

• absorbed in the duodenum and jejunum

• coverted into 5- methyltetrahydrofolate monoglutamate (5-MTHF monoglutamate) before entering portal system

• plasma folate circulates bound or unbound 

importance of B9 folate

• synthesis of purine and pyrimidine precursors of DNA

• important during periods of infancy and pregnancy for cell division

• healthy production of RBC

causes of vitamin B12 deficiency

• pernicious anaemia -impairs absorption of Italian b12 as a consequence of a reduction in intrinsic factor

• Vegans have no b12 in diet

causes of folate deficiency

• adequate presence of folate in food (rare)

• Poor dietary habits - chronic alcoholic

• Impaired absorption or metabolism or inc demand for vitamin

• Pregnancy inc need for intake of folate - more proliferating cells, 3rd trimester need for folate will x2

• drugs such as anticonvulsants can impair absorption - inc folate metabolism

consequences of folate and B12 deficiency

• spina bfida and anencephaly

• Progressive demyelination of nerve cells thought to result from inc in methylmalonyl-CoA that results from vitamin B12 deficiency

• neuropathy - spinal cord and peripheral nerves affected

• tingling in feet, difficulty w gait

• glossitis 

haemotological disorders from B12 and folate deficiency 

• megaloblastic anaemia due to folate deficiency

• Pernicious anaemia is megaloblastic anaemia due to vitamin B12 deficiency

how does b12 and folate deficiency cause megaloblastic anaemia

• deficiency of folate reduces conversion of dUMP to dTMP - rate limiting step in DNA synthesis

• DNA synthesis delayed

• RNA not delayed, protein synthesis at much faster rate

• delayed / incomplete cell division

• huge cells but less haemoglobin 

haemotological features of megaloblastic anaemia

• macrocytosis

• inc MCV > 90 fL

• dec in number of cell divisions prior to loss of nucleus

• inc lobe number in nucleus of neutrophils 

  • chromatin structural abnormalities

• oval macrocytes 

pernicious anaemia

• Autoimmune attack on the gastric mucosa

• Stomach wall becomes thin, reduces gastric secretion of acid and intrinsic factor

• Antibodies against the gastric parietal cells

test for pernicious anaemia - what increases within the haem pathway?

• methylmalonyl-coA  increases

treatment for pernicious anaemia

• oral dose of folic acid for folate deficiency

• B12 intramuscular injection of hydroxycobalmin

diagnosis for megaloblastic anaemia

• vitamin B12 deficiency must be ruled out

• if vitamin B12 deficient, folate supplementation can alleviate the anaemia but does not reverse neruological deficits

folate deficiency in serum folate

If serum folate is < 3 μg/L (< 7 nmol/L), deficiency is likely

vitamin B12 deficiency readings

A vitamin B12 level < 200 pg/mL (< 145 pmol/L) indicates vitamin B12 deficiency.