One-Carbon Metabolism - RM

Question 1

What is the precursor of dopamine?

Answer 1

tyrosine

Question 2

What is the precursor of epinephrine (E)?

Answer 2

tyrosine

Question 3

What is the precursor of melanin?

Answer 3

tyrosine

Question 4

What is the precursor of norepinephrine (NE)?

Answer 4

tyrosine

Question 5

What is the precursor of thyroxine?

Answer 5

tyrosine

Question 6

What is the precursor of GABA?

Answer 6

glutamate

Question 7

What is the precursor of histamine?

Answer 7

histidine

Question 8

What is the precursor of serotonin?

Answer 8

tryptophan

Question 9

What is the precursor of melatonin?

Answer 9

tryptophan

Question 10

What is the precursor of niacin?

Answer 10

tryptophan

Question 11

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

Answer 11

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

Question 12

How is dopamine formed from tyrosine?

Answer 12

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

Question 13

Why can’t people with atypical PKU make catechols?

Answer 13

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

Question 14

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

Answer 14

decarboxylation is always adjacent to amino group

Question 15

How is NE formed from dopamine?

Answer 15

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

Question 16

How is E formed from NE?

Answer 16

NE methylated (phenylethanolamine N-methyltransferase with SAM cofactor)

Question 17

How are catecholamines degraded?

Answer 17

monoamine oxidase

Question 18

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

Answer 18

synthesized in melanocytes, albinism

Question 19

What can a deficiency in tryptophan cause?

Answer 19

pellagra (niacin deficiency)

Question 20

How is GABA synthesized?

Answer 20

glutamate is decarboxylated (glutamate decarboxylase with pyridoxal phosphate cofactor)

Question 21

How is histamine synthesized?

Answer 21

histidine is decarboxylated (histidine decarboxylase with pyridoxal phosphate cofactor)

Question 22

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

Answer 22

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

Question 23

What kind of 1 C fragment does biotin carry?

Answer 23

CO2 groups (most oxidized)

Question 24

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

Answer 24

tetrahydrofolic acid (THF)

Question 25

What does conjugase do? Where is it located?

Answer 25

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

Question 26

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

Answer 26

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

Question 27

What is the site of action of chemotherapeutic drugs?

Answer 27

dihydrofolic acid reductase

Question 28

What is the most reduced form of THF?

Answer 28

N5-methyl-tetrahydrofolic acid

Question 29

What is the only reaction that consumes N5 methyl THF?

Answer 29

formation of methionine from homocysteine

Question 30

What is the main source of N5N10-methylene THF?

Answer 30

conversion of serine to glycine to CO2 and NH4+

Question 31

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

Answer 31

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

Question 32

What is one of the first symptoms of folate deficiency?

Answer 32

anemia

Question 33

What are 3 drugs that can cause folate deficiency?

Answer 33

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

Question 34

What does folate deficiency in pregnancy cause?

Answer 34

neural tube defects (spina bifida)

Question 35

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

Answer 35

carrier of methyl groups 1. NE to epinephrine 2. guanidinoacetate to creatine 3. acetylserotonin to melatonin 4. phosphatidylethanolamine to phosphatidylcholine 5. methylation of DNA

Question 36

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

Answer 36

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

Question 37

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

Answer 37

homocysteine methyltransferase, N5-methyl THF and vitamin B12

Question 38

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

Answer 38

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

Question 39

What can homocysteine be metabolized to besides methionine?

Answer 39

cysteine (via cystathione)

Question 40

What is homocystinuria?

Answer 40

- 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

Question 41

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

Answer 41

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

Question 42

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

Answer 42

hydrolyzes cystathione to cysteine and alpha-ketobutyrate, cystathionuria

Question 43

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

Answer 43

vitamin B12 or intrinsic factor

Question 44

Why are elderly people typically vitamin B12 deficient?

Answer 44

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

Question 45

How are forms of cobalamin (vit B12) classified?

Answer 45

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

Question 46

What two reactions involve vitamin B12?

Answer 46

1. conversion of Lmethylmalonyl CoA to succinyl coA | 2. conversion of homocysteine to methionine

Question 47

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

Answer 47

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

Question 48

What is transcobalamine?

Answer 48

transporter protein for vit. B12 in body

Question 49

What is the folate trap?

Answer 49

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

Question 50

What is the danger associated with folate supplements in grains?

Answer 50

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