B12 and Folate Flashcards
What nucleoside are both B9 and B12 used in the synthesis of?
Thymidine
Homocysteine levels are increased in what vitamin deficiencies?
B9 and B12
What enzyme converts dUridine-MP to Thymidine-MP?
Thymidylate Synthase
What is the difference between uracil and thymine?
Thymine has an extra carbon
Where does the carbon come from to make Thymidine-MP from dU-MP?
N5, N10 Tetrahydrofolate
What does N5, N10 Tetrahydrofolate become after the transfer of its carbon to make Thymidine-MP?
DHF
What enzyme converts DHF to THF?
Dihydrofolate reductase
What is Folate converted to and how is it then eventually converted to N5, N10 Tetrahydrofolate?
DHF (
tetrahydrofolate)
- THF
-> N5, N10 Tetrahydrofolate
What is the main function of N5, N10 Tetrahydrofolate?
Donates a Carbon to dUridine-MP to then become Thymidine-MP
What converts N5 Methyl THF into THF?
B12
What does S-Adenosyl Methionine (SAM) donate?
Methyl groups
What is S-Adenosyl Methionine (SAM) synthesised from?
ATP and methionine
SAM has a methyl group and Adenosine removed what does it become?
Homocysteine
B12 and Folate convert Homocysteine into what?
Methionine
Methionine + ATP yeilds what?
SAM
Methionine Synthase converts Homocysteine into what?
Methionine and Tetrahydrofolate
What are the causes of Megaloblastic anemia? (outside of B9 and B12 deficiency)
- Orotic aciduria
- Drugs (MTX, 5-FU, Hydroxyurea)
- Zidovudine (HIV, NRTIs)
What is the difference between Tetrahydrofolate and N5, N10 THF?
Addition of a carbon
- Used in thymidine synthesis
Why do alcoholics often have a folate deficiency?
- Decreased intake (nutrition)
- Poor absorption
What are the 3 drugs which interfere with folate deficiency?
- Phenytoin
- Trimethoprim
- Methotrexate
How does phenytoin cause folate deficiency?
Affects folate uptake
How can trimethoprim and Methtrexate cause folate deficiency?
Inhibiting Dihydrofolate reductase
DHF -> THF reaction
What element does cobalamin contain?
Cobalt
- Large, complex structure (corrin ring)
Where is B12 found?
Meats
- Only synthesised in bacteria
Outside of folate metabolism what is B12 also involved in?
Odd chain fatty acid metabolism
- Into Succinyl CoA
How can B12 deficiency cause peripheral neuropathy?
- Increased Methylmalonic acid
- Myelin synthesis affected
What is B12 Neuropathy called?
Subacute combined degeneration (SCD)
What part of the spinal cord is affected in B12 neuropathy?
Dorsal spinal columns
What are the symptoms of Subacute combined degeneration (SCD)?
- Bilateral
- Legs»_space; arms
- Paresthesia
- Ataxia
- Loss of vibration and position sense
- Severe weakness and paraplegia if severe
What are odd chain fatty acids converted into?
Propionyl coA
Propionyl coA is converted to Methylmalonyl CoA thru what cofactor?
Biotin
Methylmalonyl-CoA is converted to Succinyl CoA via what enzyme and cofactor?
Methylmalonyl-CoA mutase
- B12
Methylmalonyl-CoA and Succinyl CoA are similar in what way?
isomers
What substance enters the TCA cycle?
- From AAs, cholesterol,
Succinyl CoA
What vitamin is stored in the liver for years?
B12
Pernicious anemia causes the destruction of what?
Gastric parietal cells
- gastric body
What kind of HS reaction is involved in Pernicious anemia?
Type 2
What cancer is pernicious anemia associated with?
Gastric adenocarcinoma
What a HLA group is associated with Pernicious nemia?
HLA-DR antigens
What are other causes of B12 deficiency?
- ileum resection/dysfunction - Crohn’s
- Loss of IF from gastric bypass
- Diphyllobothrium latum
What is Diphyllobothrium latum?
What type of parasite?
How is it transmitted?
What does it destroy/consume?
- Helminth (tapeworm)
- Transmission from infected fish
- Consumes B12
What is the diagnostic test for pernicious anemia?
What are the steps involved?
Schilling test
- Oral radiolabeled B12
- IM B12 to saturate liver receptors
- Radiolabeled B12 should be detectable in urine normally
- Can repeat with oral IF
Radiolabeled B12 is detactable in the urine from the Schilling test
Does this individual have Pernicious anemia?
No
What cells are increased when given B12 injection?
Reticulocytes
- Immature RBCs