Nutrition Lecture 3: B12 Flashcards
What are rich food sources of B12?
Animal products! Fortified products, marmite?
What foods contain inactive forms of B12?
Tempe, mushrooms and spirulina
Where does B12 come from?
Bacteria - animals eat or absorb this bacteria
How is B12 commercially made?
Large scale production via microbial fermentation, using 3 strains of bacteria
What is vitamin B12 the term for?
All corrinoids that have biological activity of “cynanocobalamin”
What is the structure of B12?
Corrin ring (i.e. 4 pyrrole rings) with a cobalt in the centre and a dimethylbenzimidazole nucleotide
What is the molecular weight of B12?
1355g/mol - Big!
What is HC?
Haptocorrin (“R-binder”), an acid resistant glycoprotein
What is HC produced by?
Salivary glands
What is HC’s role in B12’s digestion?
HC binds to cobalamin in the stomach as soon as it is released from dietary proteins - protecting it
How is cobalamin eventually split off from the HC?
Proteases in the duodenum free the B12
What is IF?
Intrinsic factor
What is the role of IF in B12’s digestion?
IF is used as a transporter to enable B12 to enter the ileal cell
When does IF bind to B12?
After it has been released from HC in the neutralized gut
Where does IF come from?
Released from parietal cells in the stomach
Once bound to IF, what happens to B12?
It can absorbed via the intrinsic factor receptor into the ileal cell
Is cobalamin water soluble?
Yes, therefore very easily recycled
What bodily substance contains a lot of B12?
Bile
How is B12 recycled in the body?
B12 from bile is pumped out from the liver and then binds to the IF to be absorbed
What are the two active (co-factor) forms of B12?
- Methylcobalamin
- Deoxyadenosylcobalamin
What two enzymes are B12 dependent?
- Methylmalonyl-CoA mutase
- Methionine synthase
What is the role of methylmalonyl-CoA?
The conversion of methylmalonyl CoA into succinyl CoA
What is the role of methionine synthase?
To transfer methyl group from 5MTHF to homocysteine to form methionine - this regenerates the THF
A decrease in B12 causes a decrease in what enzymes activity?
MS = methionine synthase
What is the “methyl folate trap”?
The negative effects resulting from the stopped activity of the enzyme MS (methionine synthase)
Why is it called the “methyl folate trap”?
Because the folate is being stuck in the form of 5-methyl THF - cannot be regenerated into THF and methyl group cannot be used to make methionine
What are the negative effects of the “methyl folate trap”?
- 5-methyl THF levels increase
- THF levels decrease
- 5,10 methylene THF decrease
- DNA synthesis decreases
What are ways to develop B12 deficiency? (5)
- Lack of IF
- Lack of stomach acid
- GI disorders/surgery
- Metabolic defects
- Vegan/vegetarianism
What disease is caused by a lack of intrinsic factor?
Pernicious anaemia
What is pernicious anaemia?
A decrease in red blood cells when the body can’t absorb enough vitamin B12.
What can a lack of intrinsic factor be caused by?
Autoimmune disorder that attacks parietal cells - limits of eliminates the production of IF
What age group often produce less IF?
Elderly
How is a lack of intrinsic factor treated?
Intramuscular injection
A lack of stomach acid means there is limited or absent production of what?
HCl
What age group does a lack of stomach acid most often affect?
The elderly
What condition does a lack of stomach acid cause?
Atrophic gastritis - chronic inflammation of stomach mucosa
A lack of stomach acid lessens the release of what?
B12 from animal protein
What GI disease causes reduced B12 absorption?
Crohn’s disease - a type of inflammatory bowel disease
What GI surgery causes reduced B12 absorption?
Gastric bypass - may reduce the stomach area secreting stomach acid
What do inherited metabolic defects affect?
- Intestinal absorption
- Transport in blood
- Cellular uptake
- Intracellular metabolism
What must vegans do?
Take vitamin B12 supplements or B12 fortified foods - breastfed infants of vegan mothers are particularly vulnerable
What type of anaemia does B12 deficiency cause?
Megaloblastic anaemia = tiredness and breathlessness
What neural condition can B12 deficiency cause?
Peripheral neuropathy
What are the symptoms of peripheral neuropathy?
- Loss of position sense
- Spasms and weakness
- Cognitive changes
How is peripheral neuropathy caused?
Because of the impaired methylation of myelin basic protein due to deficient methionine synthase activity
What is the upper limit of B12?
“not possible to set” - there is no evidence of harm
What is the EAR for B12?
2.0ug/day
What is the RDI for B12?
2.4ug/day
