7-12 One Carbon Metabolism

Question 1

What hormones and NTs are made from which precursor amino acids?

Answer 1

Tyrosine: DA, Epi, NE, Melanin, Thyroxine
Glutamate: GABA
Histidine: Histamine
Tryptophan: Serotonin, Melatonin, Niacin

Question 2

How are catechols (DA, NE, Epi) made and what is their function?

Answer 2

First form dopa (rate limiting step): tyrosine hydroxylated to dopa via tyrosine hydroxylase (requires THB)

• DOPA –> dopamine by aromatic amino acid decarboxylase (requires pyridoxal)
• DA –> NE by dopamine b-hydroxylase (requires vit C and O2)
• NE –> Epi by phenylethanolamine methyltransferase (requires SAM)

Question 3

What is GABA and histamine?

Answer 3

• GABA is an inhibitory NT in the brain and spinal cord - formed from glutatmet by glutamate decarboxylase (pyridoxal)
• Histamine is a vasodilator released during allergic rxns - formed from histidine by histidine decarboxylase (pyridoxal)

Question 4

What are 1-carbon group carriers?

Answer 4

1. Biotin: carries CO2

2. Tetrahydrofolate (THF): accepts in degradative rxns, donor in biosyn

Question 5

What is folic acid and THF?

Answer 5

Formation of THF is dependent on folate (B vitamin in diet) - uses dihydrofolic acid reductase
- Bacteria make own folate, sulfa drugs inhibit this synthesis

Question 6

What is SAM?

Answer 6

• SAM is the major carrier of methyl groups

Question 7

Why are 1-carbon groups important?

Answer 7

Body needs them for:

• formation of methionine (from homocys)
• biosyn of purines and pyrimidines
• biosyn of glycine by glycine synthase

Question 8

What is an antifolate and what does it have to do with cancer?

Answer 8

Antifolate are drugs that block the action of folate i.e. sulfa drugs
The majority work by inhibiting dihydrofolate reductase (chemo target) –> leads to deficiency in THF in tumor cells
- Make pts deficient in folate

Question 9

What is the source of 1-carbon groups?

Answer 9

Direct contribution from glycolysis because serine can be derived from 3PG

Question 10

What is the methyl cycle?

Answer 10

Methionine is converted to SAM –> transfers CH3 to acceptor molecule and hydrolyzed to adenosine and homocysteine –> methionine regenerated from homocysteine
- Also homocysteine can form cysteine (via cystathionine synthase, deficiency leads to homocystinuria)

Question 11

What rxns use vitamin B12 (cobalamin) ?

Answer 11

B12 is a coenzyme used in:

1. Conversion of methylmalonyl CoA to succinyl CoA
2. Action of homocysteine methyltransferase (homocysteine –> methoninine)
   * B12 requires intrinsic factor, deficiencies in B12 are also a problem of intrinsic factor production

Question 12

What is pernicious anemia?

Answer 12

• Deficiency of THF and B12

- Immature RBC released into circulation

Question 13

What is the folate trap?

Answer 13

• Occurs when B12 is deficiency
• Causes a folate deficiency by trapping folate in the N5 methyl form
• Manifests as anemia
• If folate is supplemented, get neuro problems without anemia

Question 14

What are the different flavors of folate and how are they made?

Answer 14

Most reduced: CH3 group, N5
Intermediate: CH2 group, N5,N10
Most oxidized: CHO (N5), CHNH (N5), CH (N5,N10)
Formation of N5 is non-reversible in humans (used only in formation of methionine). Pts defective in this enzyme have higher risk of heart disease and lower risk of colon cancer