B12 and Folate

Question 1

What nucleoside are both B9 and B12 used in the synthesis of?

Answer 1

Thymidine

Question 2

Homocysteine levels are increased in what vitamin deficiencies?

Answer 2

B9 and B12

Question 3

What enzyme converts dUridine-MP to Thymidine-MP?

Answer 3

Thymidylate Synthase

Question 4

What is the difference between uracil and thymine?

Answer 4

Thymine has an extra carbon

Question 5

Where does the carbon come from to make Thymidine-MP from dU-MP?

Answer 5

N5, N10 Tetrahydrofolate

Question 6

What does N5, N10 Tetrahydrofolate become after the transfer of its carbon to make Thymidine-MP?

Answer 6

DHF

Question 7

What enzyme converts DHF to THF?

Answer 7

Dihydrofolate reductase

Question 8

What is Folate converted to and how is it then eventually converted to N5, N10 Tetrahydrofolate?

Answer 8

DHF (
tetrahydrofolate)
- THF
-> N5, N10 Tetrahydrofolate

Question 9

What is the main function of N5, N10 Tetrahydrofolate?

Answer 9

Donates a Carbon to dUridine-MP to then become Thymidine-MP

Question 10

What converts N5 Methyl THF into THF?

Answer 10

B12

Question 11

What does S-Adenosyl Methionine (SAM) donate?

Answer 11

Methyl groups

Question 12

What is S-Adenosyl Methionine (SAM) synthesised from?

Answer 12

ATP and methionine

Question 13

SAM has a methyl group and Adenosine removed what does it become?

Answer 13

Homocysteine

Question 14

B12 and Folate convert Homocysteine into what?

Answer 14

Methionine

Question 15

Methionine + ATP yeilds what?

Answer 15

SAM

Question 16

Methionine Synthase converts Homocysteine into what?

Answer 16

Methionine and Tetrahydrofolate

Question 17

What are the causes of Megaloblastic anemia? (outside of B9 and B12 deficiency)

Answer 17

• Orotic aciduria
• Drugs (MTX, 5-FU, Hydroxyurea)
• Zidovudine (HIV, NRTIs)

Question 18

What is the difference between Tetrahydrofolate and N5, N10 THF?

Answer 18

Addition of a carbon

- Used in thymidine synthesis

Question 19

Why do alcoholics often have a folate deficiency?

Answer 19

• Decreased intake (nutrition)

- Poor absorption

Question 20

What are the 3 drugs which interfere with folate deficiency?

Answer 20

• Phenytoin
• Trimethoprim
• Methotrexate

Question 21

How does phenytoin cause folate deficiency?

Answer 21

Affects folate uptake

Question 22

How can trimethoprim and Methtrexate cause folate deficiency?

Answer 22

Inhibiting Dihydrofolate reductase

DHF -> THF reaction

Question 23

What element does cobalamin contain?

Answer 23

Cobalt

- Large, complex structure (corrin ring)

Question 24

Where is B12 found?

Answer 24

Meats

- Only synthesised in bacteria

Question 25

Outside of folate metabolism what is B12 also involved in?

Answer 25

Odd chain fatty acid metabolism | - Into Succinyl CoA

Question 26

How can B12 deficiency cause peripheral neuropathy?

Answer 26

- Increased Methylmalonic acid | - Myelin synthesis affected

Question 27

What is B12 Neuropathy called?

Answer 27

Subacute combined degeneration (SCD)

Question 28

What part of the spinal cord is affected in B12 neuropathy?

Answer 28

Dorsal spinal columns

Question 29

What are the symptoms of Subacute combined degeneration (SCD)?

Answer 29

- Bilateral - Legs >> arms - Paresthesia - Ataxia - Loss of vibration and position sense - Severe weakness and paraplegia if severe

Question 30

What are odd chain fatty acids converted into?

Answer 30

Propionyl coA

Question 31

Propionyl coA is converted to Methylmalonyl CoA thru what cofactor?

Answer 31

Biotin

Question 32

Methylmalonyl-CoA is converted to Succinyl CoA via what enzyme and cofactor?

Answer 32

Methylmalonyl-CoA mutase | - B12

Question 33

Methylmalonyl-CoA and Succinyl CoA are similar in what way?

Answer 33

isomers

Question 34

What substance enters the TCA cycle? | - From AAs, cholesterol,

Answer 34

Succinyl CoA

Question 35

What vitamin is stored in the liver for years?

Answer 35

B12

Question 36

Pernicious anemia causes the destruction of what?

Answer 36

Gastric parietal cells | - gastric body

Question 37

What kind of HS reaction is involved in Pernicious anemia?

Answer 37

Type 2

Question 38

What cancer is pernicious anemia associated with?

Answer 38

Gastric adenocarcinoma

Question 39

What a HLA group is associated with Pernicious nemia?

Answer 39

HLA-DR antigens

Question 40

What are other causes of B12 deficiency?

Answer 40

- ileum resection/dysfunction - Crohn's - Loss of IF from gastric bypass - Diphyllobothrium latum

Question 41

What is Diphyllobothrium latum? What type of parasite? How is it transmitted? What does it destroy/consume?

Answer 41

- Helminth (tapeworm) - Transmission from infected fish - Consumes B12

Question 42

What is the diagnostic test for pernicious anemia? What are the steps involved?

Answer 42

Schilling test - Oral radiolabeled B12 - IM B12 to saturate liver receptors - Radiolabeled B12 should be detectable in urine normally - Can repeat with oral IF

Question 43

Radiolabeled B12 is detactable in the urine from the Schilling test Does this individual have Pernicious anemia?

Answer 43

No

Question 44

What cells are increased when given B12 injection?

Answer 44

Reticulocytes | - Immature RBCs