Folate (Vitamin B9) Lecture

A comprehensive set of vocabulary flashcards covering folate chemistry, absorption, transport, metabolism, functions, clinical significance, deficiency, pharmacology, and dietary aspects to aid exam preparation.

Folate (Vitamin B9)

Generic term for compounds with the biological activity of folic acid; essential water-soluble vitamin involved in one-carbon metabolism.

Folic Acid

Synthetic, fully oxidized form of folate (pteroylmonoglutamic acid) used in supplements and food fortification.

Pteroylmonoglutamic Acid

Chemical name for folic acid consisting of a pteridine ring, para-aminobenzoic acid (PABA), and one glutamate residue.

Pteridine Ring

Heterocyclic ring system forming the first part of folic acid; site of variable hydrogenation.

Para-Aminobenzoic Acid (PABA)

Middle component of folic acid linking the pteridine ring to glutamate.

Glutamic Acid Residue

Terminal amino acid in folate structure; may occur as 1–7 residues in polyglutamate folates.

Monoglutamate Folate

Folate with a single glutamate; most stable, highly bioavailable form in supplements and fortified foods.

Polyglutamate Folate

Naturally occurring folate with 2–7 (up to 12 in bacteria) glutamate residues; trapped inside cells and found in foods.

Tetrahydrofolate (THF or FH4)

Fully reduced coenzyme form of folate that accepts and donates single-carbon units.

5-Methyl-THF

Major circulating active folate coenzyme providing methyl groups for methionine synthesis.

Folate Bioavailability

Higher from synthetic folic acid (monoglutamate) than from natural food folates (polyglutamate).

Recommended Dietary Allowance (RDA)

Adults: 400 µg/day; pregnancy: 600 µg/day; lactation: 500 µg/day (values in lecture: 200–400 µg/day reference).

γ-Glutamyl Carboxypeptidase (Folyl Conjugase)

Intestinal brush-border enzyme that deconjugates dietary polyglutamate folates to monoglutamates for absorption.

Reduced Folate Carrier (RFC)

Bidirectional, pH-neutral membrane transporter that mediates folate uptake into enterocytes and tissues.

Proton-Coupled Folate Transporter (PCFT)

High-affinity folate transporter active at acidic pH, important in intestinal absorption and liver uptake.

Folate Receptor (FR/FBP)

High-affinity, GPI-anchored protein that binds folate and mediates receptor-mediated endocytosis; unidirectional into cells.

Dihydrofolate Reductase (DHFR)

Enzyme that reduces folic acid and dihydrofolate to THF; target of antifolate drugs like methotrexate.

Folylpolyglutamate Synthase

Intracellular enzyme that adds additional glutamates to THF, trapping it inside cells and enhancing enzyme affinity.

One-Carbon Metabolism

Series of reactions where THF coenzymes carry and transfer single-carbon units for amino acid, nucleotide, and methyl group synthesis.

S-Adenosylmethionine (SAM)

Universal methyl donor formed from methionine; its synthesis requires 5-methyl-THF and vitamin B12.

Methylenetetrahydrofolate Reductase (MTHFR)

Enzyme converting 5,10-methylene-THF to 5-methyl-THF; mutations raise homocysteine levels.

Methionine Synthase

Vitamin B12-dependent enzyme that transfers the methyl group from 5-methyl-THF to homocysteine, forming methionine.

Formiminotransferase

Cytosolic enzyme transferring a formimino group from FIGLU to THF in histidine catabolism; FIGLU accumulates in folate deficiency.

Thymidylate Synthase

Enzyme converting dUMP to dTMP using 5,10-methylene-THF; required for DNA synthesis.

Purine Synthesis

De novo pathway requiring 10-formyl-THF for two formylation steps in IMP formation.

DNA Methylation

Epigenetic regulation involving SAM-dependent methylation of cytosine; influenced by folate status.

Megaloblastic Anemia

Macrocytic anemia with hypersegmented neutrophils caused by impaired DNA synthesis from folate or B12 deficiency.

Neural Tube Defects (NTDs)

Birth defects of brain and spinal cord (e.g., spina bifida) preventable by adequate maternal folate intake.

Hyperhomocysteinemia

Elevated plasma homocysteine linked to cardiovascular disease, hypertension, and neurodegeneration; often due to low folate/B12/B6.

Cardiovascular Disease Risk

Moderately elevated homocysteine from low folate associated with coronary, peripheral, and carotid atherosclerosis.

Antifolate Drugs

Compounds that inhibit folate metabolism; include methotrexate, aminopterin, sulfasalazine, phenytoin, and trimethoprim.

Methotrexate

Folate analog with high affinity for DHFR; blocks THF regeneration, inhibiting DNA synthesis; used in cancer, psoriasis, RA.

Aminopterin

Early antifolate (rodenticide) structurally similar to methotrexate; inhibits DHFR.

Sulfasalazine

Anti-inflammatory drug that impairs folate absorption and utilization.

Phenytoin (Diphenylhydantoin)

Anticonvulsant that interferes with folate metabolism and can cause deficiency.

Metformin

Antidiabetic drug that may reduce folate and B12 absorption, elevating homocysteine.

Plasmodium falciparum

Malaria parasite that requires folate for DNA synthesis; treated with antifolate antimalarials.

Folate Deficiency Causes

Poor intake, alcoholism, malabsorption (celiac, sprue, jejunal resection), increased demand (pregnancy, lactation, hemolysis), or drug therapy.

Folate Deficiency Consequences

Impaired DNA/RNA synthesis, megaloblastic anemia, weakness, depression, neuropathy, spontaneous abortion, birth defects, elevated homocysteine.

Folate Toxicity

Oral excess considered safe; very high parenteral doses may provoke seizures or zinc malabsorption in rare cases.

FIGLU Test

Clinical determination of formiminoglutamate excretion after histidine load; elevated in folate deficiency.

Dietary Folate Sources – Plant

Green leafy vegetables (spinach, lettuce, broccoli), mushrooms, avocado, citrus fruits, beans, soy.

Dietary Folate Sources – Animal

Organ meats (liver, kidney), eggs; milk and erythrocytes largely contain 5-methyl-THF.

Fortified Foods

Flour, breads, ready-to-eat breakfast cereals containing added folic acid to prevent deficiency.

Increased Folate Requirements

Third trimester pregnancy and rapid cell turnover conditions double daily folate need (~800 µg/day).

Brush-Border pH Range

Intestinal γ-glutamyl carboxypeptidase functions optimally at pH 6.5 – 7.0 to deconjugate folate.

Cellular Folate Trap

Intracellular polyglutamylation prevents folate efflux, raising local coenzyme concentrations for metabolic reactions.