One Carbon Metabolism

Front 1

What is one-carbon metabolism?

Back 1

the use of single carbon units (-CH3, -CH2OH, -CHO) in biosynthetic reactions

Front 2

What is the source of the one carbon units?

Back 2

amino acids and choline

Front 3

What serves as a carrier of the one-carbon group?

Back 3

folate (tetrahydrofolate), vitamin B12 (methylcobalamin), and methionine (S-adenosylmethionine)

Front 4

When is one-carbon metabolism active and where does it occur?

Back 4

fed and fasting states, in nearly all cells

Front 5

Dietary folate, polyglutamate folate, is converted to monoglutamate folate by a reaction catalyzed by what enzyme?

Back 5

folate hydroxylase, a brush border enzyme

Front 6

What causes folate deficiency?

Back 6

diet; alcohol consumption, overcooking vegetables, not eating vegetables

Front 7

How does alcohol consumption cause folate deficiency?

Back 7

blocks import of monoglutamic folic acid into intestinal cells

Front 8

What enzyme catalyzes the activation of folate?

Back 8

dihydrofolate reductase uses NADPH to form tetrahydrofolate (THF) from folate

Front 9

What is the impact of methotrexate on folate?

Back 9

methotrexate is a competetive inhibitor of dihydrofolate reductase (prevents activation of folate to THF), inhibits thymidine synthesis, slows RBC cell division

Front 10

What is the source of carbons attached to THF, where are the carbons attached?

Back 10

serine is the source, one-carbon units are attached to the N5 and/or N10 nitrogens of THF

Front 11

What form of THF is the major source of folate for tissues?

Back 11

N5-methyl THF

Front 12

What are the functions of the one-carbon units on THF?

Back 12

purine synthesis, thymidine synthesis, methionine regeneration, serine and glycine synthesis

Front 13

Beside THF, what is another carrier of one-carbon units, which is more versatile?

Back 13

S-adenosylmethionine (SAMe) is more versatile than THF, used in 350 reactions (99% of methyl transfers)

Front 14

What does SAMe become after it donates its methyl group?

Back 14

homocysteine

Front 15

What is homocysteine converted to, and what is the enzyme that catalyzes the reaction (with associated vitamins)?

Back 15

homocysteine methyltransferase catalyzes synthesis of methionine from homocysteine, requires N5-methyl THF and B12

Front 16

How does a vitamin B12 deficiency cause folate deficiency?

Back 16

vitamin B12 is required for homocysteine methyl transferase to convert homocysteine to methionine, when this process is blocked both homocysteine and N5 methyl THF accumulate (locks up folate in this form)

Front 17

What does nitrous oxide (N2O) do to vitamin B12?

Back 17

deactivates it by oxidizing the cobalt

Front 18

What are the three pathologies associated with vitamin B12 deficiency?

Back 18

pernicious anemia, peripheral neuropathy, personality changes

Front 19

What are the three main pathologies associated with folate deficiency?

Back 19

megaloblastic anemia, birth defects, cancer

Front 20

What is the transsulfuration pathway?

Back 20

homocysteine not used to form methionine is used to synthesize cysteine by adding sulfur to serine, requires vitamin B6

Front 21

What is the rate limiting enzyme of the transsulfuration pathway and how is it regulated?

Back 21

cystathionine synthase is the rate limiting ezyme, allosterically activated by SAMe (prevents synthesis of excess methionine)

Front 22

What is homocystinuria and how is it treated?

Back 22

autosomal recessive disease that causes a defect in cystathionine synthase (causes cysteine deficiency), affects eyes, skeleton, CNS, vasculature, treated with vitamins B6, B12, folate, and restriction of methionine