Lesson 1.4. Folic Acid Pharmacology

amino acids, purines, and DNA

ROLE OF FOLIC ACID IN BIOCHEMISTRY:

• Reduced forms of folic acid are crucial for synthesizing ____________________________________, which are vital for cell growth and division.

megaloblastic anemia

DEFICIENCY RISKS OF FOLIC ACID:

• leads to a.______________________

• linked to b.__________________________ in newborns

• contribute to c.________________________________

a = ?

congenital malformations

DEFICIENCY RISKS OF FOLIC ACID:

• leads to a.______________________

• linked to b.__________________________ in newborns

• contribute to c.________________________________

b = ?

vascular diseases

DEFICIENCY RISKS OF FOLIC ACID:

• leads to a.______________________

• linked to b.__________________________ in newborns

• contribute to c.________________________________

c = ?

yeast, liver, kidney, and green vegetables

SOURCES OF FOLIC ACID:

• found in a.______________________________________

• typical American diet provides b._____________________ of folates daily

a = ?

500-700 mcg

SOURCES OF FOLIC ACID:

• found in a.______________________________________

• typical American diet provides b._____________________ of folates daily

b = ?

proximal jejunum

ABSORPTION OF FOLIC ACID:

• It is absorbed in the a.______________________, while dietary folates such as b.__________________________ need to be converted into c._____________________________.

a = ?

polyglutamates

ABSORPTION OF FOLIC ACID:

• It is absorbed in the a.______________________, while dietary folates such as b.__________________________ need to be converted into c._____________________________.

b = ?

monoglutamates

ABSORPTION OF FOLIC ACID:

• It is absorbed in the a.______________________, while dietary folates such as b.__________________________ need to be converted into c._____________________________.

c = ?

Dihydrofolate

DNA SYNTHESIS:

1. Folic Acid is reduced to a.______________________ by the enzyme b._______________________.

2. Dihydrofolate is converted to c.___________________ by the enzyme d._______________________.

3. Tetrahydrofolate accepts a 1-carbon unit from e.____________ by the enzyme f.______________________________ to yield g.__________ as by-product and h.___________________________ which is used for i.______ synthesis.

4. N⁵,N¹⁰-Methylenetetrahydrofolate transfers its methyl group to j.____________________ by the enzyme k.______________, generating l._____________________ as a by-product.

5. This will generate m.______________________ for n.______________ synthesis, which will regenerate Dihydrofolate, restarting the cycle.

a = ?

Folate reductase

DNA SYNTHESIS:

1. Folic Acid is reduced to a.______________________ by the enzyme b._______________________.

2. Dihydrofolate is converted to c.___________________ by the enzyme d._______________________.

3. Tetrahydrofolate accepts a 1-carbon unit from e.____________ by the enzyme f.______________________________ to yield g.__________ as by-product and h.___________________________ which is used for i.______ synthesis.

4. N⁵,N¹⁰-Methylenetetrahydrofolate transfers its methyl group to j.____________________ by the enzyme k.______________, generating l._____________________ as a by-product.

5. This will generate m.______________________ for n.______________ synthesis, which will regenerate Dihydrofolate, restarting the cycle.

b = ?

Tetrahydrofolate

DNA SYNTHESIS:

1. Folic Acid is reduced to a.______________________ by the enzyme b._______________________.

2. Dihydrofolate is converted to c.___________________ by the enzyme d._______________________.

3. Tetrahydrofolate accepts a 1-carbon unit from e.____________ by the enzyme f.______________________________ to yield g.__________ as by-product and h.___________________________ which is used for i.______ synthesis.

4. N⁵,N¹⁰-Methylenetetrahydrofolate transfers its methyl group to j.____________________ by the enzyme k.______________, generating l._____________________ as a by-product.

5. This will generate m.______________________ for n.______________ synthesis, which will regenerate Dihydrofolate, restarting the cycle.

c = ?

Dihydrofolate reductase

DNA SYNTHESIS:

1. Folic Acid is reduced to a.______________________ by the enzyme b._______________________.

2. Dihydrofolate is converted to c.___________________ by the enzyme d._______________________.

3. Tetrahydrofolate accepts a 1-carbon unit from e.____________ by the enzyme f.______________________________ to yield g.__________ as by-product and h.___________________________ which is used for i.______ synthesis.

4. N⁵,N¹⁰-Methylenetetrahydrofolate transfers its methyl group to j.____________________ by the enzyme k.______________, generating l._____________________ as a by-product.

5. This will generate m.______________________ for n.______________ synthesis, which will regenerate Dihydrofolate, restarting the cycle.

d = ?

Serine

DNA SYNTHESIS:

1. Folic Acid is reduced to a.______________________ by the enzyme b._______________________.

2. Dihydrofolate is converted to c.___________________ by the enzyme d._______________________.

3. Tetrahydrofolate accepts a 1-carbon unit from e.____________ by the enzyme f.______________________________ to yield g.__________ as by-product and h.___________________________ which is used for i.______ synthesis.

4. N⁵,N¹⁰-Methylenetetrahydrofolate transfers its methyl group to j.____________________ by the enzyme k.______________, generating l._____________________ as a by-product.

5. This will generate m.______________________ for n.______________ synthesis, which will regenerate Dihydrofolate, restarting the cycle.

e = ?

Serine transhydroxymethylase

DNA SYNTHESIS:

1. Folic Acid is reduced to a.______________________ by the enzyme b._______________________.

2. Dihydrofolate is converted to c.___________________ by the enzyme d._______________________.

3. Tetrahydrofolate accepts a 1-carbon unit from e.____________ by the enzyme f.______________________________ to yield g.__________ as by-product and h.___________________________ which is used for i.______ synthesis.

4. N⁵,N¹⁰-Methylenetetrahydrofolate transfers its methyl group to j.____________________ by the enzyme k.______________, generating l._____________________ as a by-product.

5. This will generate m.______________________ for n.______________ synthesis, which will regenerate Dihydrofolate, restarting the cycle.

f = ?

serine

DNA SYNTHESIS:

1. Folic Acid is reduced to a.______________________ by the enzyme b._______________________.

2. Dihydrofolate is converted to c.___________________ by the enzyme d._______________________.

3. Tetrahydrofolate accepts a 1-carbon unit from e.____________ by the enzyme f.______________________________ to yield g.__________ as by-product and h.___________________________ which is used for i.______ synthesis.

4. N⁵,N¹⁰-Methylenetetrahydrofolate transfers its methyl group to j.____________________ by the enzyme k.______________, generating l._____________________ as a by-product.

5. This will generate m.______________________ for n.______________ synthesis, which will regenerate Dihydrofolate, restarting the cycle.

g = ?

N⁵,N¹⁰-Methylenetetrahydrofolate

DNA SYNTHESIS:

1. Folic Acid is reduced to a.______________________ by the enzyme b._______________________.

2. Dihydrofolate is converted to c.___________________ by the enzyme d._______________________.

3. Tetrahydrofolate accepts a 1-carbon unit from e.____________ by the enzyme f.______________________________ to yield g.__________ as by-product and h.___________________________ which is used for i.______ synthesis.

4. N⁵,N¹⁰-Methylenetetrahydrofolate transfers its methyl group to j.____________________ by the enzyme k.______________, generating l._____________________ as a by-product.

5. This will generate m.______________________ for n.______________ synthesis, which will regenerate Dihydrofolate, restarting the cycle.

h = ?

Purine

DNA SYNTHESIS:

1. Folic Acid is reduced to a.______________________ by the enzyme b._______________________.

2. Dihydrofolate is converted to c.___________________ by the enzyme d._______________________.

3. Tetrahydrofolate accepts a 1-carbon unit from e.____________ by the enzyme f.______________________________ to yield g.__________ as by-product and h.___________________________ which is used for i.______ synthesis.

4. N⁵,N¹⁰-Methylenetetrahydrofolate transfers its methyl group to j.____________________ by the enzyme k.______________, generating l._____________________ as a by-product.

5. This will generate m.______________________ for n.______________ synthesis, which will regenerate Dihydrofolate, restarting the cycle.

i = ?

deoxyuridine monophosphate (dUMP)

DNA SYNTHESIS:

1. Folic Acid is reduced to a.______________________ by the enzyme b._______________________.

2. Dihydrofolate is converted to c.___________________ by the enzyme d._______________________.

3. Tetrahydrofolate accepts a 1-carbon unit from e.____________ by the enzyme f.______________________________ to yield g.__________ as by-product and h.___________________________ which is used for i.______ synthesis.

4. N⁵,N¹⁰-Methylenetetrahydrofolate transfers its methyl group to j.____________________ by the enzyme k.______________, generating l._____________________ as a by-product.

5. This will generate m.______________________ for n.______________ synthesis, which will regenerate Dihydrofolate, restarting the cycle.

j = ?

Thymidylate synthase

DNA SYNTHESIS:

1. Folic Acid is reduced to a.______________________ by the enzyme b._______________________.

2. Dihydrofolate is converted to c.___________________ by the enzyme d._______________________.

3. Tetrahydrofolate accepts a 1-carbon unit from e.____________ by the enzyme f.______________________________ to yield g.__________ as by-product and h.___________________________ which is used for i.______ synthesis.

4. N⁵,N¹⁰-Methylenetetrahydrofolate transfers its methyl group to j.____________________ by the enzyme k.______________, generating l._____________________ as a by-product.

5. This will generate m.______________________ for n.______________ synthesis, which will regenerate Dihydrofolate, restarting the cycle.

k = ?

N⁵-Methyltetrahydrofolate

DNA SYNTHESIS:

1. Folic Acid is reduced to a.______________________ by the enzyme b._______________________.

2. Dihydrofolate is converted to c.___________________ by the enzyme d._______________________.

3. Tetrahydrofolate accepts a 1-carbon unit from e.____________ by the enzyme f.______________________________ to yield g.__________ as by-product and h.___________________________ which is used for i.______ synthesis.

4. N⁵,N¹⁰-Methylenetetrahydrofolate transfers its methyl group to j.____________________ by the enzyme k.______________, generating l._____________________ as a by-product.

5. This will generate m.______________________ for n.______________ synthesis, which will regenerate Dihydrofolate, restarting the cycle.

l = ?

deoxythymidine monophosphate (dTMP)

DNA SYNTHESIS:

1. Folic Acid is reduced to a.______________________ by the enzyme b._______________________.

2. Dihydrofolate is converted to c.___________________ by the enzyme d._______________________.

3. Tetrahydrofolate accepts a 1-carbon unit from e.____________ by the enzyme f.______________________________ to yield g.__________ as by-product and h.___________________________ which is used for i.______ synthesis.

4. N⁵,N¹⁰-Methylenetetrahydrofolate transfers its methyl group to j.____________________ by the enzyme k.______________, generating l._____________________ as a by-product.

5. This will generate m.______________________ for n.______________ synthesis, which will regenerate Dihydrofolate, restarting the cycle.

m = ?

DNA

DNA SYNTHESIS:

1. Folic Acid is reduced to a.______________________ by the enzyme b._______________________.

2. Dihydrofolate is converted to c.___________________ by the enzyme d._______________________.

3. Tetrahydrofolate accepts a 1-carbon unit from e.____________ by the enzyme f.______________________________ to yield g.__________ as by-product and h.___________________________ which is used for i.______ synthesis.

4. N⁵,N¹⁰-Methylenetetrahydrofolate transfers its methyl group to j.____________________ by the enzyme k.______________, generating l._____________________ as a by-product.

5. This will generate m.______________________ for n.______________ synthesis, which will regenerate Dihydrofolate, restarting the cycle.

n = ?

donating one-carbon units

Tetrahydrofolate is involved in important biochemical reactions, particularly in _______________________ essential for various metabolic processes.

building block of DNA

Deoxythymidine monophosphate (dTMP) is a ________________________.

active form

Tetrahydrofolate serves as the _________________ of folic acid

One-Carbon Transfer Reactions

ROLE OF TETRAHYDROFOLATE IN BIOCHEMISTRY:

• Tetrahydrofolate cofactors are essential for _____________________________, including the synthesis of dTMP required for DNA synthesis

dTMP Synthesis Cycle

ROLE OF TETRAHYDROFOLATE IN BIOCHEMISTRY:

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

Target of Anti-Cancer Drugs

ROLE OF TETRAHYDROFOLATE IN BIOCHEMISTRY:

• The enzymes in the dTMP cycle are targeted by drugs like methotrexate (inhibits dihydrofolate reductase) and 5-fluorouracil (inhibits thymidylate synthase)

Megaloblastic Anemia

CLINICAL CONSEQUENCES OF FOLATE DEFICIENCY:

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

serum

DIAGNOSIS OF FOLATE DEFICIENCY:

• assessed through a._________________

• b.____________________ often provide more accurate diagnostic information

a = ?

red blood cell folate assays

DIAGNOSIS OF FOLATE DEFICIENCY:

• assessed through a._________________

• b.____________________ often provide more accurate diagnostic information

a = ?

Alcohol Dependence, Liver Disease, or Malabsorption Syndromes

CAUSES AND RISK FACTORS OF FOLIC ACID DEFICIENCY:

• Inadequate Dietary Intake: Folate Deficiency is often due to poor diet, especially in individuals with ___________________________________.

Pregnant women, Patients with Hemolytic Anemia, and Chronic Conditions

CAUSES AND RISK FACTORS OF FOLIC ACID DEFICIENCY:

• Increased Requirements: ___________________________ may have increased folate requirements

Methotrexate, Trimethoprim, Pyrimethamine, and Phenytoin

CAUSES AND RISK FACTORS OF FOLIC ACID DEFICIENCY:

• Drug-Induced Deficiency: Certain medications like _____________________________________ can inhibit folate metabolism and lead to deficiency

oral dose of 1 mg

TREATMENT OF FOLIC ACID DEFICIENCY:

• A daily a.______________________ folic acid is usually sufficient to reverse deficiency and restore normal folate levels.

• b.____________________________ is rarely necessary.

a = ?

Parenteral administration

TREATMENT OF FOLIC ACID DEFICIENCY:

• A daily a.______________________ folic acid is usually sufficient to reverse deficiency and restore normal folate levels.

• b.____________________________ is rarely necessary.

b = ?

pregnant women, alcohol dependent patients, and patients on renal dialysis

FOLIC ACID SUPPLEMENTATION:

• Considered for high-risk groups including: