One-Carbon Metabolism Flashcards Preview

Biochemistry - Sarah > One-Carbon Metabolism > Flashcards

Flashcards in One-Carbon Metabolism Deck (45):
1

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

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

2

Biotin
1) C1 source
2) C1 group
3) Reactions

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

3

SAM
1) C1 source
2) C1 group
3) Reactions

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

4

FH4
1) C1 source
2) C1 group
3) Reactions

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

5

Biotin is required for ____.

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)

6

Sources of biotin in diet

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

7

What does Biotinidase do?

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)

8

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

Holocarboxylase synthetase deficiency

9

Holocarboxylase synthetase deficiency can result in _____.

encephalopathic crisis (brain damage) and hair loss

10

SAM stands for

S-Adenosylmethionine

11

SAM

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

12

One carbon carriers

SAM, FH4, and Biotin

13

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

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

14

Fate of S-Adenosyl homocysteine

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

15

FH4 stands for

tetrahydrofolate

16

FH4 function

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

17

A deficiency of vitamin B9 is associated with

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)

18

FH4 is required for the synthesis of ___.

dTMP

19

Folate is converted to ____ using ____.

Tetrahydrofolate using dihydrofolate reductase. NADPH required.

20

Where is FH4 stored?

The liver

21

Folate is absorbed in its ____ form.

Monoglutamate

22

Where do single carbon units bind on FH4?

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

23

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

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

purine and pyrimidine synthesis

24

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

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

25

Dietary sources of folic acid

green vegetables, yeast, liver, some fruits

26

A deficiency in folic acid can be caused by

alcoholism, malabsorption diseases

27

Antifolates are being considered as

Antitumor agents

28

Antifolate example

Methotrexate

29

Methotrexate

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

30

Reactions dependent on vitamin B12

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

Removes methyl from N5methyl-FH4

(Vitamin B12 is cobalamin)

31

How can cobalamin deficiency be detected?

Ingest radioactive Co-B12 to measure absorption

32

Dietary sources of B12

meat, dairy

33

Pathway of dietary B12 to the bloodstream

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)

34

What can happen when achlorhydia occurs?

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

35

Vitamin B12 deficiency causes ___.

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

36

Hyperhomocysteinemia (symptoms)

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)

37

What are causes of vitamin B12 deficiency?

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

38

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

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

39

What are megaloblasts?

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.

40

What causes hyperhomocysteinemia?

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

41

Mutations in cystathione beta-synthase cause ____.

homocystinuria, a rare extreme form of hyperhomocysteinemia

42

Homocystinuria is caused by ____.

A mutation in cystathione beta-synthase

43

Symptoms of homocystinuria

eye lens dislocation, Marfan-like symptoms

44

Alternate pathway for homocysteine to methionine

betaine

45

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

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