Biochemistry: folic acid & B12
Vitamins → water soluble → B complex → (folic acid & B12)
Nutritional anemias → Macrocytic low MCV → deficiency in B12 and folate B9
Folic acid (also known as B9 or pteroyl-glutamic acid))
Folate, the anion of folic acid,
made up of three different components:
1. Pteridine derivative.
2. 4-aminobenzoate PABA
(contain carboxyl groups→ responsible for the acidity of folate)
3. One or more glutamate residues. (R) (amino acid)
Plays a key role in one-carbon metabolism.
Essential for the biosynthesis of several compounds.
Most common deficiency in the USA in women(pregnancy) and
alcoholics
Folic acid is a light-sensitive molecule
(due to the presence of the rings in its structure)
active form of folic acid:
tetrahydrofolate (THF)
Have different structures that differ
due to functional groups' variety
we are unable to synthesize folic acid (we lack specific enzymes),
we *depend on normal flora to do primary steps and then converted
to its active form in the liver
*or consumed by food (green vegetables)
absorbed by the upper part of the(( jejunum))
transported in the blood by Beta globins → Liver conversion to the
co-enzyme
*Not stored in tissues
, THF synthesis
*microorganisms glutamate
dihydropteroate
synthetase
Pteridine + p-aminobenzoic acid folic acid
Precursor PABA
X
sulfonamide
*sulfonamide competitively inhibits the synthesis of folic acid in
microorganisms and → thereby decreases the synthesis of nucleotides
needed for the replication of DNA
**humans + microorganisms
2NADH + 2H+ 2NADP+
Dihydrofolate this step happens twice
reductase
Folic acid tetrahydro folic acid *amino acid synthesis
(folic acid + 4H+) *purine synthesis
X *DNA…
Thymidine mono-
Methotrexate phosphate synthesis
*Dihydrofolate reductase is competitively inhibited by methotrexate, a folic
acid analogue
NADH + H+ NADP+ NADH + H+ NADP+
Dihydrofolate Dihydrofolate
Reductase reductase
Diet folic acid dihydrofolic THF
Acid
X X
Methotrexate Methotrexate
Methotrexate → X synthesis of DNA → used to treat psoriasis, rheumatoid
arthritis, and neoplastic diseases
Cancer cells might become resistant to methotrexate, by duplicating the
gene of the enzyme itself
Vitamins → water soluble → B complex → (folic acid & B12)
Nutritional anemias → Macrocytic low MCV → deficiency in B12 and folate B9
Folic acid (also known as B9 or pteroyl-glutamic acid))
Folate, the anion of folic acid,
made up of three different components:
1. Pteridine derivative.
2. 4-aminobenzoate PABA
(contain carboxyl groups→ responsible for the acidity of folate)
3. One or more glutamate residues. (R) (amino acid)
Plays a key role in one-carbon metabolism.
Essential for the biosynthesis of several compounds.
Most common deficiency in the USA in women(pregnancy) and
alcoholics
Folic acid is a light-sensitive molecule
(due to the presence of the rings in its structure)
active form of folic acid:
tetrahydrofolate (THF)
Have different structures that differ
due to functional groups' variety
we are unable to synthesize folic acid (we lack specific enzymes),
we *depend on normal flora to do primary steps and then converted
to its active form in the liver
*or consumed by food (green vegetables)
absorbed by the upper part of the(( jejunum))
transported in the blood by Beta globins → Liver conversion to the
co-enzyme
*Not stored in tissues
, THF synthesis
*microorganisms glutamate
dihydropteroate
synthetase
Pteridine + p-aminobenzoic acid folic acid
Precursor PABA
X
sulfonamide
*sulfonamide competitively inhibits the synthesis of folic acid in
microorganisms and → thereby decreases the synthesis of nucleotides
needed for the replication of DNA
**humans + microorganisms
2NADH + 2H+ 2NADP+
Dihydrofolate this step happens twice
reductase
Folic acid tetrahydro folic acid *amino acid synthesis
(folic acid + 4H+) *purine synthesis
X *DNA…
Thymidine mono-
Methotrexate phosphate synthesis
*Dihydrofolate reductase is competitively inhibited by methotrexate, a folic
acid analogue
NADH + H+ NADP+ NADH + H+ NADP+
Dihydrofolate Dihydrofolate
Reductase reductase
Diet folic acid dihydrofolic THF
Acid
X X
Methotrexate Methotrexate
Methotrexate → X synthesis of DNA → used to treat psoriasis, rheumatoid
arthritis, and neoplastic diseases
Cancer cells might become resistant to methotrexate, by duplicating the
gene of the enzyme itself
