C1 metabolism

Question 1

Overview of C1 metabolism

Answer 1

Requires THF (folate = B9)

Donated by serine, histidine, formate (COOH)
-> intermediates Formyl THF, methyl/ene/nyl-THF
(all reversible except -> N5-methyl-THF)

N5-methyl-THF -> SAM ->
N5,N10-methlene -> thymidylate -> pyrimidines
N10-formyl-THF -> purines

Question 2

Folic acid

Answer 2

Synthesized in bacteria (essential for us)

Folate -di-hydro-folate reductase> tetrahydrofolate (THF)

Carries C1 side groups:

• CH3 methyl = most reduced
• CH2- methylene
• CHO (formyl) or CHNH (formimino) = oxidized

Question 3

Donation of C1

Answer 3

Most from serine
Glycolysis -> 3-P-glycerate ->
serine + THF -hydroxymethyl-transferase> glycine + N5N10-methylene THF

Also
Hist -> 5-formimino-THF -> N5N10-methenyl-THF + Glut

Question 4

Methionine metabolism

Answer 4

N5N10methylene-THF -> N5methyl-THF
(irreversible!)

Homocysteine + N5-methyl-THF -> Met + THF
(requires cobalamin/B12)

Met + ATP -> S-adenosylMet (SAM) = “activated” methyl
-> creatine, carnitine, epinephrine (from NE)
(ex phosphatidyl serine + 3SAM -> phos-choline)
SAM -donates methyl> SAH -> adenosine + homocysteine

Question 5

Folate trap

Answer 5

Folate = THF
N5N10-methylene-THF -reductase> N5-methyl-THF
= IRREVERSIBLE

N5-methyl-THF used for homocys -> Met
This reaction requires B12 (cobalamin)

Low B12 -> THF is “trapped” as N5-methyl-THF (accumulates)

• also see accumulation of homocysteine
• > similar sx to low folate (megaloblastic anemia)