Vitamin B9 and B12

Question 1

The active form of Vitamin B9/Folic acid is ________.

Answer 1

tetrahydrofolate (FH4 or THF)

Question 2

sources of folic acid

Answer 2

~ Green leaves/vegetables, liver, kidney, fish, nuts, legumes, whole germ cereals
~ in mammals it may also be produced by microorganisms in their intestinal tracts
Why do mammals obtain folic acid from the diet or from microorganisms in their intestinal tracts yet we are able to synthesize the pteridine ring?

Question 3

tetrahydofolate consists of three groups: …

Answer 3

a substituted pteridine, p-aminobenzoate and a glutamate residue [Diagram]

Question 4

role of folic acid

Answer 4

1. It interacts with vitamin B12 and vitamin C in the formation of blood.
2. Tetrahydrofolate is a highly versatile carrier of activated one-carbon units. [The one-carbon group carried by tetrahydrofolate is bonded to its N-5 or N-10 nitrogen atom (denoted as N5 and N10) or to both.] The one carbon groups carried include: methyl, methylene, methenyl, formyl and formimino groups. The fully oxidized one-carbon unit, CO2, is carried by biotin rather than by tetrahydrofolate.
3. dTMP (deoxythymidine monophosphate) is formed by methylation of dUMP (deoxyuridine monophosphate). The donor of a methylene group and a hydride in this reaction is N5, N10 methylenetetrahydrofolate, which is converted into dihydrofolate.
4. Tetrahydrofolate is regenerated by the reduction of dihydrofolate by NADPH (nicotinamide adenine dinucleotide phosphate).
5. Biosynthesis of purines and pyrimidines.
6. Required in the synthesis of DNA.

Question 5

metabolism of tetrahydrofolate

Answer 5

• The synthesis of TMP can be blocked by inhibiting the regeneration of tetrahydrofolate. [TMP stands for trimethoprim. Trimethoprim is an antibiotic that inhibits the regeneration of tetrahydrofolate, an essential cofactor in nucleic acid synthesis. By blocking this process, trimethoprim interferes with bacterial growth and is commonly used to treat various infections.]
• Analogs of dihydrofolate, such as aminopterin and methotrexate (amethopterin), are potent competitive inhibitors of dihydrofolate reductase.
• Tetrahydrofolate plays a role in the biosynthesis of purines and pyrimidines.
• Rapidly dividing cells require an abundant supply of thymidylate for the synthesis of DNA. The vulnerability of these cells to the inhibition of TMP (trimethoprim) synthesis has been exploited in cancer chemotherapy. Thymidylate synthase and dihydrofolate reductase are choice targets of chemotherapy.
• Fluorouracil, a clinically useful anticancer drug, is converted in vivo into fluorodeoxyuridylate (F-dUMP). This analog of dUMP irreversibly inhibits thymidylate synthase after acting as a normal substrate through part of the catalytic cycle.
• Sulfanilamide inhibits the synthesis of folate by acting as an analog of p-aminobenzoate, one of the precursors of folate (in pathogens). [you’ll discuss it as an inhibitor in enzymes]

Question 6

deficiency complications of Vitamin B9

Answer 6

• Folate deficiency causes macrocytic anemia (MCAN) where red blood cells (RBCs) are enlarged and reduced in number.
• Folic acid is a precursor of tetrahydrofolate required in the biosynthesis of glycine, a precursor of porphyrins. A folic acid deficiency therefore impairs hemoglobin synthesis.

Question 7

Cobalamin has ____________ and ____________.

Answer 7

corrin ring and benzimidazole [Diagram]

Question 8

source of Vitamin B12 aka. cobalamin

Answer 8

foods of animal origin, especially meat and liver

Question 9

What is the role of Vitamin B12 in metabolism?

Answer 9

• The 5-deoxyadenosyl derivative [5’-deoxyadenosylcobalamin is a coenzyme form of vitamin B12] is required for the methylmalonyl coA mutase reaction, which is a key step in catabolism of some branched chain amino acids.
• Resynthesis of methionine is a methylcobalamin-dependent reaction. [methionine is an essential amino acid]
• The methyl derivative of vitamin B12 is required for conversion of homocysteine to methionine. [homocysteine is an amino acid]

Question 10

Deficiency complications of Vitamin B12?

Answer 10

pernicious anemia, a megaloblastic anemia associated with neurological deterioration
[deficiencies are extremely rare]

Question 11

Malabsorption of vitamin B12 can be due to:
A) high levels of the vitamin
B) high levels of branched chain amino acids
C) lack of intrinsic factor in the body
D) lack of meat in the diet
E) presence of HCl in the stomach