[PHA 6126 LEC] Part 3: Pharmacology of Vitamin B12 and Folic Acid

Vitamin B12 (as methylcobalamin)

What facilitates the transfer of a methyl group from N5-methyltetrahydrofolate to homocysteine, producing methionine?

Methylfolate Trap

What happens when there is a deficiency in Vitamin B12?

tetrahydrofolate

DNA synthesis

Fill in the blank:

Without Vitamin B12, N5-methyltetrahydrofolate cannot be converted to ____, leading to a shortage of folate cofactors needed for ____.

Megaloblastic Anemia

It arises due to inadequate DNA synthesis in rapidly dividing cells

Folic Acid

It can help correct anemia by providing tetrahydrofolate through an alternate pathway but not prevent neurologic symptoms of B12 deficiency

High homocysteine levels

What can the deficiency of B vitamins lead to?

T

T or F

High homocysteine levels may increase cardiovascular disease risk. Although supplements may lower their levels, they do not lower the risk of cardiovascular disease

Methylmalonic Acid accumulation, Neurological damage, Folic Acid limitation

What can the deficiency of Methylmalonyl-CoA mutase cause?

megaloblastic and microcytic anemia (often accompanied by leukopenia, thrombocytopenia, and hypercellular bone marrow)

What kind of deficiencies is Vitamin B12 used to treat or prevent?

It starts with paresthesias and progresses to central nervous system dysfunction

What is the typical progression pattern of neurological symptoms in Vitamin B12 deficiency if left untreated?

By measuring serum vitamin levels

How can laboratory tests distinguish vitamin B12 deficiency from folate deficiency in megaloblastic anemia?

Schilling test

Historically used to identify malabsorption of

vitamin B12 due to lack of intrinsic factor or other

gastrointestinal issues, but it is now rarely performed.

Vitamin B12 deficiency

What does pernicious anemia, partial or total gastrectomy, malabsorption syndromes, inflammatory bowel disease, or small bowel resection commonly cause?

Pernicious anemia

It is caused by defective secretion of intrinsic factor due to gastric atrophy and autoantibodies, leading to diminished vitamin B12 absorption even with added intrinsic factor.

Parenteral therapy

Type of treatment required in most vit B12 cases due to malabsorption issues

T

T or F

Initial parenteral therapy consists of 100-1000 mcg of vit B12 IM daily or every other day for 1-2 weeks. Maintenance

therapy is 100-1000 mcg IM once a month for life.

Oral doses (1000mcg) daily and intranasal administration

Aside from parenteral therapy, what alternative treatments are available for vitamin B12 deficiency?

Hydroxycobalamin

It is favored over cyanocobalamin due to its longer retention in the circulation.

Reduced forms of folic acid

Crucial for synthesizing amino acids, purines, and DNA, which are vital for cell growth and division.

F

megaloblastic anemia

Folate deficiency can lead to pernicious anemia and is linked to malformations in newborns and vascular diseases.

Folic acid

It is made up of a heterocycle (pteridine), p-aminobenzoic acid, and glutamic acid and converted into dihydrofolic acid then into tetrahydrofolate through reduction.

Tetrahydrfolate

It is involved in donating one-carbon units essential for various metabolic processes.

Yeast, liver, kidney, and green vegetables

Where can folic acid be sourced from?

Proximal jejunum

Where is folic acid absorbed?

F

monoglutamates

T or F

Dietary folates (primary polyglutamates) need to be converted into diglutamates for absorption

5-20 mg, mainly in the liver

Where are most folate stores located in the body, and how much is stored?

1-6 months, depending on nutritional status and folate utilization rate

How long does it take for folate deficiency to develop if intake stops?

Vitamin B12

What does the monoglutamate form of folate (N 5-methyltetrahydrofolate) need for it to be converted to tetrahydrofolate?

One-carbon transfer reactions, dTMP synthesis cycle, and serves as a target of anti-cancer drugs

What are the main roles of tetrahydrofolate in biochemistry?

dTMP Synthesis Cycle

What cycle involves thymidylate synthase, dihydrofolate reductase, and serine transhydroxymethylase and is critical for DNA synthesis, especially in rapidly proliferating tissues?

Methotrexate

What drug targets enzymes in the dTMP cycle and inhibits dihydrofolate reductase?

5-fluorouracil

What drug targets enzymes in the dTMP cycle and inhibits thymidylate synthase?

Megaloblastic anemia

It is similar in appearance to anemia caused by vitamin B12 deficiency but without the associated neurological symptoms

T

T or F

Folate status is assessed through serum or red blood cell folate assays, with red blood cell folate levels often providing more accurate diagnostic information.

Folate

Which nutrient has increased requirements in pregnant women, patients with hemolytic anemia, and those with certain chronic conditions?

Methotrexate, trimethoprim, pyrimethamine, and long-term phenytoin use

What drugs can inhibit folate metabolism and lead to deficiency?

F

1 mg daily

T or F

Taking 5mg of folic acid orally every other day can reverse deficiency and restore normal folate levels.