One-Carbon Metabolism

Question 1

Be able to recognize methyl, carboxyl, formyl, and methenyl groups

Answer 1

methyl - CH3
carboxyl - COOH
formyl - CHO
methenyl - CH (double bond)

Question 2

Biotin

1) C1 source
2) C1 group
3) Reactions

Answer 2

1) CO2
2) carboxyl group (COOH)
3) Carboxylations

Question 3

SAM

1) C1 source
2) C1 group
3) Reactions

Answer 3

1) Methionine
2) Methyl group (CH3)
3) Methylations

Question 4

FH4

1) C1 source
2) C1 group
3) Reactions

Answer 4

1) Tryptophan, Serine, and Glycine
2) formyl group, methenyl group, methylene group, and methyl group (FH4 only performs one methylation reaction)
3) Synthesis of purines, pyrimidines, and thymidine; homocysteine to methionine

Question 5

Biotin is required for ____.

Answer 5

Carboxylases
namely: pyruvate carboxylase (pyruvate to oxaloacetate)
acetyl CoA carboxylase (produces malonyl CoA from acetyl CoA, ketone body synthesis)
propionyl CoA carboxylase (key enzyme in catabolism of branched chain amino acids)
(Also beta-methylcrotonyl CoA carboxylase which is a part of leucine catabolism)

Question 6

Sources of biotin in diet

Answer 6

Fish, peanuts, chocolate, eggs, yeast, liver, milk, intestinal bacteria
Raw egg whites can cause biotin deficiency (avidin)

Question 7

What does Biotinidase do?

Answer 7

It is present in cells and serum and cleaves biotin from proteins to recycle biotin. Biotinidase deficiency causes symptoms of biotin deificiency (seizures, hypotonia, ataxia)

Question 8

_____ can result in encephalopathic crisis (brain damage) and hair loss.

Answer 8

Holocarboxylase synthetase deficiency

Question 9

Holocarboxylase synthetase deficiency can result in _____.

Answer 9

encephalopathic crisis (brain damage) and hair loss

Question 10

SAM stands for

Answer 10

S-Adenosylmethionine

Question 11

SAM

Answer 11

S-Adenosylmethioine is a major carrier of methyl groups in metabolism

Question 12

One carbon carriers

Answer 12

SAM, FH4, and Biotin

Question 13

What are acceptors and products that are part of SAM methylation reactions?

Answer 13

Guanidoacetic acid --> creatine
Phosphatidylethanolamine --> Phosphatidylcholine
rRNA, tRNA --> methylated RNA
Norepinephrine --> Epinephrine
Protein-bound lys --> Trimethyllysine

Question 14

Fate of S-Adenosyl homocysteine

Answer 14

Hydrolyzed to adenosine and homocysteine
Homocysteine is converted to methionine or used in cysteine synthesis.
Vitamin B12, or cobalmin, is a cofactor

Question 15

FH4 stands for

Answer 15

tetrahydrofolate

Question 16

FH4 function

Answer 16

Major carrier of single carbons groups in metabolism. Reduced form of folic acid

Question 17

A deficiency of vitamin B9 is associated with

Answer 17

Spina bifida (vitamin B9 is folic acid) (if the mother is not receiving enough folic acid)

Impairment of DNA replication that affects rapidly dividing cells; macrocytic anemia, megaloblasts (oversized RBC precursors in bone marrow, subtype of macrocytic anemia)

Question 18

FH4 is required for the synthesis of ___.

Answer 18

dTMP

Question 19

Folate is converted to ____ using ____.

Answer 19

Tetrahydrofolate using dihydrofolate reductase. NADPH required.

Question 20

Where is FH4 stored?

Answer 20

The liver

Question 21

Folate is absorbed in its ____ form.

Answer 21

Monoglutamate

Question 22

Where do single carbon units bind on FH4?

Answer 22

to the N5 and N10 sites. Carbon atoms in different oxidation states attach differently to FH4. Methyl groups bind to N5 and formyl groups bind to N10. Methenyl and methylene groups form carbon bridges between N5 and N10

Question 23

Tetrahydrofolate transfers single carbon units from ______ and donates them to acceptos that are intermediates in _____.

Answer 23

Tryptophan, histidine, glycine, and serine as well as formaldehyde and formate (intermediates in aa degradation)

purine and pyrimidine synthesis

Question 24

True or false: All FH4 derivatives are easily interconverted, reversible reactions.

Answer 24

Not quite true. Most are, but 5-methyl-FH4 is not.

Question 25

Dietary sources of folic acid

Answer 25

green vegetables, yeast, liver, some fruits

Question 26

A deficiency in folic acid can be caused by

Answer 26

alcoholism, malabsorption diseases

Question 27

Antifolates are being considered as

Answer 27

Antitumor agents

Question 28

Antifolate example

Answer 28

Methotrexate

Question 29

Methotrexate

Answer 29

Antitumor agent used to treat people, analog of folic acid. Inhibits dihydrofolate reductase which converts dihydrovolate to tetrahydrofolate. 5-fluorouracil inhibits thymidylate synthase (methylation of UMP to dTMP) and it stops cell division of rapidly dividing tumor cells

Question 30

Reactions dependent on vitamin B12

Answer 30

Homocysteine to methionine (mehtyl-cobalamin), methylmalonyl CoA to succinyl CoA (Adenosyl cobalamin)

Removes methyl from N5methyl-FH4

(Vitamin B12 is cobalamin)

Question 31

How can cobalamin deficiency be detected?

Answer 31

Ingest radioactive Co-B12 to measure absorption

Question 32

Dietary sources of B12

Answer 32

meat, dairy

Question 33

Pathway of dietary B12 to the bloodstream

Answer 33

proteases release B12 from protein and it is bound by haptocorrins (R-binders). Proteases release B12 from haptocorrins and it is bound by intrinsic factor (protein), attaches to receptors and enters through the terminal segment of the small intestine (ileum)

Question 34

What can happen when achlorhydia occurs?

Answer 34

Reduced B12 absorption (acid is required to release B12 from protein)

Question 35

Vitamin B12 deficiency causes ___.

Answer 35

Megaloblastic anemia, neurological deterioration (pernicious anemia is B12 deficiency caused by lack of intrinsic factor)
Caused by reduced pool of tetrahydrofolate (N5methyl-FH4 cannot be converted to FH4)

Elevated methylmalonyl CoA

Question 36

Hyperhomocysteinemia (symptoms)

Answer 36

Too much homocysteine in blood. Higher risk of coronary heart disease, stroke, periopheral vascular disease. (Increased carotid plaque thickness, associated with low B12 levels as well)

Question 37

What are causes of vitamin B12 deficiency?

Answer 37

Vegan diet, pernicious anemia (lack of intrinsic factor), Chron’s disease (intestinal malabsorption), and bariatric surgery

Question 38

What is the difference between folate deficiency and vitamin B12 deficiency?

Answer 38

B12 deficiency has neurological symptoms not present in folate deficiency. High methymalonyl CoA in serum may cause neurological symptoms by decreasing lipid synthesis, or might be due to decreased SAM

Question 39

What are megaloblasts?

Answer 39

They form in bone marrow. Most are destroyed in bone marrow. Cause macrocytic anemia. DNA synthesis is inhibited (DTTP limiting due to folate deficiency) but RNA synthesis continues. RBCs appear that are abnormally large and irregular shape (macrocytes). Elevated hypersegmented neutrophils in peripheral blood are characteristic of megaloblastic anemia.

Question 40

What causes hyperhomocysteinemia?

Answer 40

Folate deficiency, B12 deficiency, mutation in cystathione beta-synthase

Question 41

Mutations in cystathione beta-synthase cause ____.

Answer 41

homocystinuria, a rare extreme form of hyperhomocysteinemia

Question 42

Homocystinuria is caused by ____.

Answer 42

A mutation in cystathione beta-synthase

Question 43

Symptoms of homocystinuria

Answer 43

eye lens dislocation, Marfan-like symptoms

Question 44

Alternate pathway for homocysteine to methionine

Answer 44

betaine

Question 45

Why are there neurological symptoms in B12 deficiency but not in folate deficiency? (possibility)

Answer 45

The brain does not have the betaine pathway to form methionine.