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U6 MCP > One-Carbon Metabolism - RM > Flashcards

One-Carbon Metabolism - RM Flashcards

1
Q

What is the precursor of dopamine?

A

tyrosine

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2
Q

What is the precursor of epinephrine (E)?

A

tyrosine

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3
Q

What is the precursor of melanin?

A

tyrosine

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4
Q

What is the precursor of norepinephrine (NE)?

A

tyrosine

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5
Q

What is the precursor of thyroxine?

A

tyrosine

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6
Q

What is the precursor of GABA?

A

glutamate

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7
Q

What is the precursor of histamine?

A

histidine

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8
Q

What is the precursor of serotonin?

A

tryptophan

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9
Q

What is the precursor of melatonin?

A

tryptophan

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10
Q

What is the precursor of niacin?

A

tryptophan

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11
Q

What is the rate limiting step of catecholamine biosynthesis? What is it inhibited by?

A

tyrosine hydroxylation to dopa (1st step), allosteric inhibition by dopamine, NE, epinephrine (E)

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12
Q

How is dopamine formed from tyrosine?

A

tyrosine hydroxylated to dopa (tyrosine hydroxylase with tetrahydrobiopterin cofactor)
dopa decarboxylated to dopamine (aromatic acid decarboxylase with pyroxidal phosphate cofactor)

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13
Q

Why can’t people with atypical PKU make catechols?

A

they can’t regenerate tetrahydrobiopterin from dihydrobiopterin so can’t hydroxylate tyrosine (1st step in catecholamine biosynthesis)

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14
Q

What happens in reactions with pyridoxal phosphate (PLP) cofactor?

A

decarboxylation is always adjacent to amino group

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15
Q

How is NE formed from dopamine?

A

dopamine is hydroxylated (dopamine beta hydroxylase with Cu, ascorbate, and molecular oxygen cofactors)

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16
Q

How is E formed from NE?

A

NE methylated (phenylethanolamine N-methyltransferase with SAM cofactor)

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17
Q

How are catecholamines degraded?

A

monoamine oxidase

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18
Q

Where is melanin produced? What is a defect in melanin production called?

A

synthesized in melanocytes, albinism

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19
Q

What can a deficiency in tryptophan cause?

A

pellagra (niacin deficiency)

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20
Q

How is GABA synthesized?

A

glutamate is decarboxylated (glutamate decarboxylase with pyridoxal phosphate cofactor)

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21
Q

How is histamine synthesized?

A

histidine is decarboxylated (histidine decarboxylase with pyridoxal phosphate cofactor)

22
Q

What 4 things does the body need 1 C fragments for?

A
  1. formation of methionine from homocysteine
  2. biosynthesis of purines
  3. biosynthesis of pyrimidines
  4. biosynthesis of glycine from CO2 and NH4+ by glycine synthase
23
Q

What kind of 1 C fragment does biotin carry?

A

CO2 groups (most oxidized)

24
Q

What carries 1 C groups of all oxidation states except CO2?

A

tetrahydrofolic acid (THF)

25
Q

What does conjugase do? Where is it located?

A

cleaves the gamma-peptidyl linked glutamates off of folate (from diet) to leave just one glutamate moiety to make it easier to absorb, in the intestinal mucosal cells

26
Q

What type of cells use a lot of folate? Why do they use a lot of folate?

A

rapidly dividing cells, need folate to make nucleotides for DNA synthesis

27
Q

What is the site of action of chemotherapeutic drugs?

A

dihydrofolic acid reductase

28
Q

What is the most reduced form of THF?

A

N5-methyl-tetrahydrofolic acid

29
Q

What is the only reaction that consumes N5 methyl THF?

A

formation of methionine from homocysteine

30
Q

What is the main source of N5N10-methylene THF?

A

conversion of serine to glycine to CO2 and NH4+

31
Q

What is the serine to glycine reaction a direct connection between?

A

glycolysis (G3P–> serine) to 1 Carbon pool (N5N10-methylene-THF)

32
Q

What is one of the first symptoms of folate deficiency?

A

anemia

33
Q

What are 3 drugs that can cause folate deficiency?

A

oral contraceptive, barbituates from impaired absorption, methotrexate inhibits dihydrofolate reductase

34
Q

What does folate deficiency in pregnancy cause?

A

neural tube defects (spina bifida)

35
Q

What is S-adenosylmethionine (SAM)? What are 5 examples of reactions it acts as a cofactor for?

A

carrier of methyl groups

  1. NE to epinephrine
  2. guanidinoacetate to creatine
  3. acetylserotonin to melatonin
  4. phosphatidylethanolamine to phosphatidylcholine
  5. methylation of DNA
36
Q

What happens in the activated methyl cycle? (2 steps)

A
  1. adenosyl of ATP transferred to sulfur of methionine converting it to SAM
  2. Methyl attached to S of SAM transferred to acceptor to give methylated product and SA-homocysteine
37
Q

What enzyme regenerates methionine from homocysteine? What are the cofactors?

A

homocysteine methyltransferase, N5-methyl THF and vitamin B12

38
Q

What are elevated levels of homocysteine associated with? What 3 things reduce homocysteine levels?

A

increased risk for atherosclerosis, vitamin B12, folate (THF) and pyroxidal phosphate reduce homocysteine by helping to activate enzymes that reduce it

39
Q

What can homocysteine be metabolized to besides methionine?

A

cysteine (via cystathione)

40
Q

What is homocystinuria?

A
  • deficiency in cystathione beta-synthetase enzyme or pyroxidal phosphate cofactor that catalyzes homocysteine to cystathione conversion
  • deficiency in homocysteine methyltransferase, THF, or vit. B12 can cause it too
41
Q

Why can pyroxidal phosphate (PLP) be used to treat homocystinuria?

A

some forms are due to inadequate binding of PLP cofactor to enzyme, by adding more PLP it reduces the deficiency

42
Q

What does gamma-cystathionase do? What does a deficiency in it cause?

A

hydrolyzes cystathione to cysteine and alpha-ketobutyrate, cystathionuria

43
Q

Pernicious (megaloblastic) anemia is associated with a deficiency in…

A

vitamin B12 or intrinsic factor

44
Q

Why are elderly people typically vitamin B12 deficient?

A

secrete less intrinsic factor which is necessary to bind and absorb vit. B12

45
Q

How are forms of cobalamin (vit B12) classified?

A

by the group attached to the 5th bone above the plane of the ring

46
Q

What two reactions involve vitamin B12?

A
  1. conversion of Lmethylmalonyl CoA to succinyl coA

2. conversion of homocysteine to methionine

47
Q

How do you supplement vitamin B12 in a patient with low intrinsic factor?

A

injections of vitamin B12 so already in bloodstream and doesn’t need to be absorbed into it using intrinsic factor

48
Q

What is transcobalamine?

A

transporter protein for vit. B12 in body

49
Q

What is the folate trap?

A

when vit. B12 is deficient, folate is trapped in N5-methyl THF form
N5 methyl THF only used in homocysteine to methionine and if you don’t have vitamin B12 homocysteine methyl transferase can’t run that reaction

50
Q

What is the danger associated with folate supplements in grains?

A

if you have vit. B12 deficiency, folate builds up as N5 methyl THF
if you supplement with folate, you will keep accumulating more N5 methyl THF as you use the folate supplement so won’t be anemic but will have irreversible neurological damage from N5 methyl THF

U6 MCP (26 decks)

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