M1-C1-L66 --> One Carbon Metabolism

Front 1

What are the three parts of THF?

Back 1

1. 6-methylpterin
2. PABA (p-aminobenzoate)
3. Glutamate

Front 2

Folate is synthesized by what?

Back 2

Plants and bacteria

Front 3

What is the maximum number of glutamates that can be attached to THF?

Back 3

8

Front 4

1 carbon units in varying oxidation states are carried at which Nitrogens?

Back 4

N5 and/or N10

Front 5

What is the order of successive additions in folate?

Back 5

PABA to 6-methylpterin. Then glutamate residues.

Front 6

What does sulfonamide antibiotics do?

Back 6

Inhibit the addition of PABA to 6-methylpterin.

Front 7

Sulfonamides are specific to what organism and why?

Back 7

Bacteria. Not in humans or vertebrates b/c don't synthesize folate.

Front 8

What is the enzyme responsible for folate synthesis in microorganisms?

Back 8

Dihydropteroate Synthetase

Front 9

What is the enzyme responsible for THF synthesis in humans?

Back 9

Dihydrofolate Reductase (DHFR)

Front 10

In the synthesis of THF, where do the reducing electrons come from?

Back 10

NADPH of the pentose pathway

Front 11

Additions of 1 carbon units on THF allows for what type of synthesis. x 3

Back 11

1. Purine synthesis
2. Amino Acid synthesis
3. Thymidine synthesis

Front 12

What inhibits the enzyme DHFR and how?

Back 12

Methotrexate and aminopterin act as folate analogs to competitively inhibit DHFR.

Front 13

What is the main source of methyl groups on THF?

Back 13

Serine

Front 14

Where on Folate is there reduction to become THF?

Back 14

Nitrogen 5, 6, 7, 8

Front 15

What enzyme allows serine to donate methyl group?

Back 15

Serine hydroxymethyl transferase

Front 16

Serine + THF --> ?

Back 16

N5, N10 Methylene THF

Front 17

What is the enzyme that allows for N5, N10 Methylene THF to become N5 Methyl THF?

Back 17

N5, N10 Methylene THF Reductase

Front 18

What is the most reduced form of THF?

Back 18

N5 Methyl THF

Front 19

What is unusual about the THF reaction in TMP synthesis?

Back 19

N5, N10 Methylene THF not only provides a 1C unit, but it ALSO reduces the donated unit to a methyl group. Thus producing DHF

Front 20

What prevents DHF to becoming THF?

Back 20

Methotrexate

Front 21

When should there be increased folate requirements?

Back 21

During lactation and pregnancy.

Front 22

What would be some causes for insufficiency of intestinal absorption of folate?

Back 22

1. Intestinal pathology
2. Alcoholism

Front 23

Name a birth defect and anemia that is caused by folate deficiency?

Back 23

1. Neural Tube Deficiency
2. Megaloblastic (macrocytic) anemia

Front 24

For a person with macrocytic anemia, what happens to hematopoietic cells?

Back 24

Cell division requires folate. Thus, a person with folate deficiency will have hematopoietic cells arrested in S phase of cell cycle.

Front 25

Even on marginal diets deficient in folate, not all mothers gave birth to babies with NTD's. Why?

Back 25

Folate deficient NTD's result usually result from a common gene polymorphism in the gene for 5, 10 Methylene THF Reductase. Even though it is common, not having this polymorphism can lead to a baby without NTD's.

Front 26

What is the only cobalt-containing compound that participates in human metabolism.

Back 26

Vitamin B12 or Cobalamin

Front 27

Describe the importance of methylcobalamin in the intersection of vitamin B12 and THF metabolism.

Back 27

Methylcobalamin is a B12 coenzyme required for synthesis of methionine.

Methylcobalamin gets its methyl group from N5 methyl THF. In the absence of B12, this folate becomes trapped in this compound since the reduction leading to 5 methyl THF is irreversible.

Front 28

Describe the importance of 5'-deoxyadenosylcobalamin in the intersection of vitamin B12 and THF metabolism.

Back 28

This is the coenzyme required in propionate oxidation, which is important in catabolism of amino acids and fatty acids with odd number carbons.

Front 29

How do you make SAM (S-adenosyl Methionine)?

Back 29

ATP + Methionine

Front 30

How do you get from SAM to SAH (S-adenosyl Homocysteine)?

Back 30

SAM donates a methyl group.

Front 31

How do you go from SAH to Hcy (Homocysteine)

Back 31

SAH gives up an adenosine.

Front 32

How does Hcy become methionine?

Back 32

Hcy picks up a methyl group from the B12 sitting on methionine synthase. This methyl group is replenished from N5-methyl THF

Front 33

In small cases, what melecule might substitute for N5-methyl THF in methionine synthesis?

Back 33

Betaine

Front 34

Describe SAM's ability to donate methyl group compared to N5-methyl THF?

Back 34

SAM is 1000x's more active as a methyl donor.

Front 35

SAM participates as methyl donor in which reactions/pathways? x5

Back 35

1. Phospholipid synthesis
2. Amino acid derivative synthesis
3. Catecholamine metabolism
4. Post-translational protein methylation
5. DNA methylation

Front 36

SAM acts as an allosteric inhibitor of what? x2

Back 36

1. Inhibitor of methylene THF reductase (MTHFR)
2. Inhibitor betaine Hcy methyl transferase

Front 37

SAM acts as an allosteric activator of what?

Back 37

Activator of cystathionine synthase (enzyme that catalyzes condensation of Hcy to serine)

Front 38

What regulates SAM synthesis?

Back 38

SAM

Front 39

When SAM levels are high, methyl donors are ?

Back 39

Decreased

Front 40

When SAM levels are high, homocysteine is used in what?

Back 40

Cysteine synthesis

Front 41

When SAM levels are low, methyl donors are?

Back 41

Abundant

Front 42

When SAM levels are low, homocysteine is used in what?

Back 42

Methionine synthesis.

Front 43

Hyperhomocysteinemia (elevated plasma Hcy) has what type of consequence? x3

Back 43

1. Homocystinuria
2. Pregnancy disorders
3. Vascular damage.