One Carbon Metabolism

Question 1

What are the two key methyl group donors?

Answer 1

THF and SAM

Question 2

Donates methyl groups in de novo purine synthesis and thymidylate synthesis

Answer 2

THF

Question 3

Donates a methyl group in epinephrine synthesis and DNA methylation

Answer 3

SAM

Question 4

All natural folates are conjugated to a polyglutamyl chain and are commonly called

Answer 4

Polyglutamates

Question 5

Converts polyglutamase to monoglutamate (folate) for absorption

Answer 5

Folate conjugase

Question 6

Folate conjugase is inhibited by

Answer 6

Phenytoin

Question 7

Which two things inhibit monoglutamate uptake?

Answer 7

Oral Contraceptives (OCPs) and alcohol

Question 8

Essential for adequate absorption of dietary folates

Answer 8

Conjugase

Question 9

Conjugase production may be compromised by

Answer 9

Bowel irritation

Question 10

Bowel irritation probably arising from bacterial origin, causes intestinal inflammation and malabsorption

Answer 10

Tropical Sprue

Question 11

Similar outcome, but the original irritation is due to an allergic response, for example to gliaden (a component in gluten)

Answer 11

Celiac Sprue

Question 12

Inhibit dihydrofolate reductase (DHFR) which converts folate to THF

Answer 12

Methotrexate and Aminopterin

Question 13

An inhibitor of THF synthesis

Answer 13

Methotrexate

Question 14

Potent chemotherapeutic agent and treatment for autoimmune disorders that competitively inhibits Dihydrofolate Reductase (DHFR)

Answer 14

Methotrexate

Question 15

Can adversely affect normal dividing cells of the body

Answer 15

Methotrexate

Question 16

Due to toxicities associated with high dose methotrexate therapy, hat can be used to bypass the metabolic block of methotrexate?

Answer 16

Folinic acid (leucorvin)

Question 17

Effective at combating the neurotoxicity, GI toxicity, and myelosuppression effects of methotrexate

Answer 17

Folinic acid (leucorvin)

Question 18

The active form of folate

Answer 18

Folinic acid

Question 19

More highly polyglutamated in cancer cells than normal cells

Answer 19

Methotrexate

Question 20

The more highly polyglutamation increases cancer cells methotrexate affinity for

Answer 20

DHFR

Question 21

Accumulates more readily in normal cells than cancer cells

Answer 21

Leucorvorin

Question 22

Can be converted to THF by bypassing DHFR

Answer 22

Leucorvorin

Question 23

The sulfonamide antibiotics selectively kill bacterial cells by inhibiting

Answer 23

DHPS

Question 24

An enzyme unique to bacteria, that is essential for THF synthesis

Answer 24

DHPS

Question 25

Also selectively kills bacteria by preferentially inhibiting bacterial DHFR compared with the same enzyme in humans

Answer 25

Trimethoprim

Question 26

A patient presents with a urinary tract infection and is prescribed a combination drug containing trimethoprim and sulfamethoxazole. These drugs are effective because they do what?

Answer 26

Inhibit bacterial THF synthesis

Question 27

The type of molecule from which THF takes a Carbon group determines the reaction in which it can

Answer 27

Participate in

Question 28

For example, N-Formyl-THF can only be used in

Answer 28

Purine synthesis

Question 29

Or, in the case of N,N-Methylene-THF, the THF only participates in

Answer 29

Thymidylate synthesis

Question 30

The megaloblastic anemia of a patient with folate deficiency is most likely cause by a decreased conversion of

Answer 30

dUMP to dTMP

Question 31

After donating its methyl group SAM becomes S-adenosyl homocysteine, which is quickly hydrolyzed to

Answer 31

Homocysteine

Question 32

Elevations in plasma homocysteine levels promote

Answer 32

Oxidative damage, inflammation, and endothelial dysfunction

Question 33

An independent risk factor for occlusive vascular disease

Answer 33

Homocysteine

Question 34

Plasma homocysteine levels are inversely related to levels of

Answer 34

Folate, B12, and B6

Question 35

Used in the conversion of homocysteine to cysteine

Answer 35

B6

Question 36

To clear homocysteine, we get the reaction of homocysteine + N-methylTHF which yields methionine and THF. This reaction requires

Answer 36

B12

Question 37

Slows the conversion of Homocysteine and N5MethylTHF to Methionine and THF

Answer 37

B12 deficiency

Question 38

Thus, the cell’s folate supplies become trapped as

Answer 38

N-methylTHF

Question 39

Without THF available to make other folates, we see a depletion in the supply of cell

Answer 39

Nucleotides

Question 40

A Vitamin B12 deficiency can lead to the accumulation of

Answer 40

Methylmalonyl CoA

Question 41

Elevated levels of homocysteine and methylmalonic acid are biomarkers for

Answer 41

B12 deficiency

Question 42

The catabolism of valine and isoleucine as well as the degradation of odd-chain fatty acids leads to

Answer 42

Propionyl CoA

Question 43

Propionyl CoA is converted to

Answer 43

Methylmalonyl CoA

Question 44

Degraded to succinyl CoA via a B12 dependent reaction

Answer 44

Methylmalonyl CoA

Question 45

Can be used in the citric acid cycle

Answer 45

Succinyl CoA

Question 46

What are the consequences of B12 deficiency?

Answer 46

Macrocytic anemia, peripheral neuropathy, spinal cord degeneration, ataxia

Question 47

A smooth, sore tongue, with atrophy of the papillae signifies

Answer 47

B12 deficiency

Question 48

Failure to regenerate methionine prevents SAM regeneration, this means no -important to myelin maintanence

Answer 48

Methylation

Question 49

Identical to B12 deficiency, except there is no neurological disease

Answer 49

Folate deficiency

Question 50

Elevations in homocysteine, but not methylmalonic acid, and also an enlarged tongue, are symptoms of

Answer 50

Folic acid deficiency