Unit 6 - One Carbon Metabolism Flashcards Preview

Molecular and Cellular Princples of Medicine > Unit 6 - One Carbon Metabolism > Flashcards

Flashcards in Unit 6 - One Carbon Metabolism Deck (40):
1

what biologically important compounds can be made from tyrosine?

dopamine, norepinephrine - nt
epinephrine, thyroxine - hormone
melanin - pigment

2

what biologically important compounds can be made from glutamate?

GABA - nt

3

what biologically important compounds can be made from histidine?

histamine - vasodilator

4

what biologically important compounds can be made from tryptophan?

melatonin - hormone
serotonin - vasoconstrictor
niacin - vitamin
also makes oxidized nicotinamide adenine dinucleotide (NAD+)

5

formation of dopa (dihydroxyphenylalanine)
-what cofactors are needed?

1. tyr is hydroxylated to dopa by tyrosine hydroxylase with tetrabiopterin cofactor

6

what is the rate-limiting step of catecholamine biosynthesis?

tyrosine hydroxylase (tyrosine --> dopa); mixed function enzyme
-enzyme is allosteric, with dopamine, NE, and E acting as negative effectors

7

how is dopamine formed from dopa?

aromatic AA decarboxylase (PLP dependent)

8

how is NE formed from dopamine? what are its cofactors?

dopamine-beta hydroxylase (mixed function enzyme)
-has Cu, and needs vit C and O2

9

how is E formed from NE? what is needed?

phenylethanolamine N-methyltransferase
-uses SAM as methyl donor

10

how are catechols degraded?

monoamine oxidase
-inhibitors of MAO used as antidepressants

11

biosynthesis of melanins
-defect

biological pigments; made only in melanocytes
-made from tyrosine by sequence of several RXNs divergent from catechols
-albinism if cannot convert tyrosine to melanin

12

what amino acid can cause B3 deficiency?

tryptophan (since precursor to B3) can cause pellagra

13

how is GABA made from glutamate? what are its cofactors?

L-glutamate --glutamate decarboxylase--> GABA + CO2
-requires PLP

14

how is hidstamine made?

histidine --histidine decarboxylase--> histamine + CO2

15

how do antihistamine drugs work?

are compounds that are structurally similar to histamine to prevent physiologic changes it normally produces

16

what does the body need single carbon fragments for?

1. form met from homocysteine
2. biosynthesis of purines
3. biosynthesis of pyrimidines
4. biosynthesis of glycine from CO2 and NH4+ by glycine synthase

17

what are the one-carbon carriers?

-biotin
-tetrahydrofolate
-S-adenosylmethionine

18

what is biotin?

carrier of CO2 (most oxidized 1 C group)

19

what is tetrahydrofolate?

carries 1 C groups of all oxidation states except CO2 (most oxidized)
-serves as acceptor of 1-C fragments in degradative reactions, and as donor of 1-C fragments in biosynthetic RXNs

20

why can't humans make tetrahydrofolate?

cannot make pterin ring, so THF formation dependent on folate (pteroylglutamate, folic acid) intake

21

how is THF made from the diet?

dietary folate is usually polyglutamines, with moieties attached in gamma-peptidyl linkages
-cleaved by conjugase (in intestinal mucosal cells) to leave single glutamate moiety on absorbed vitamin
-reduced via 2-step dihydrofolic acid reductase, using up 2 NADPH+

22

how many protons does the active form of THF have?

4: has them on positions 5, 6, 7, and 8 of ring

23

what do sulfa drugs do?

inhibit biosynthesis of folate by mimicking p-amino benzoic acid

24

what are the different oxidation states, groups, and carriers for 1-carbons?

most reduced: CH3 methyl via N-5
intermediate: CH2 methylene via N-5/10
-most oxidized: CHO formyl, CHNH formino, CH methenyl via N-5 (and N-10 for methenyl)

25

what is the significance of N5-methyl-THF?

formation by N5,N10-methylene-THF reductase is non-reversible in humans, and consumed in only one reaction to make methionine
-more than 12% of population is partially deficient in this enzyme
--have higher risk of heart disease, lower risk of colon cancer (b/c can't make as many nucleotides)

26

what are some drugs that cause folate deficiency?

-oral contraceptives
-barbiturates (impairs absorption and utilization)
-methotrexate, aminopterin (antimetabolite used in cancer chemotherapy)
--inhibit dihydrofolate reductase, to cause deficiency in THF in rapidly dividing cells that need it for nucleotide synthesis
--most vulnerable are bone marrow, hair follicles, and GI mucosa with limited THF

27

what is S-adenosylmethionine?

the major carrier of methyl groups, and important methyl donor to variety of biomolecules

28

what are 5 of the 30+ reactions SAM is involved in?

-NE --> E
-guanidinoacetate --> creatine
-acetylserotonin --> melatonin
-phosphatidylethanolamine --> phosphatidylcholine
-methylation of DNA

29

what are elevated levels of homocysteine correlated with?

increased risk of atherosclerosis
-vitamin supplementation with B12, folate, and PLP can reduce levels by activating enzymes that remove it

30

how is methionine regenerated from homocysteine? cofactors involved?

homocysteine methyltransferase; needs B12
-methyl group is donated by N5-methyl-THF
-B12 is methylated to methylcobalamin form, which donates to homocysteine to make methionine
-deficiency can cause homocystinuria

31

what does cystathionase do? deficiency?

hydrolyzes cystathionine to cysteine and a-KG
-deficiency causes cystathioninuria

32

what is the central core of B12?

tetrapyrrole with central cobalt atom bonded to 4 pyrrole nitrogens
-5th bond is to 5'-deoxyadenosine unit above plane of the molecule
-6th bond to dimethylbenzimidazole

33

what do most B12 vitamin supplements have structure wise?

CN group in 5th bond above plane of the ring

34

what are the 2 reactions in the human body that need cobalamin? what form are they in?

1. MMCoA to SCoA via MMCoA mutase (adenosyl form)
2. homocystine to methionine via homocystine methyltransferase (hydroxy form)

35

what does deficiency of THF and B12 lead to?

megaloblastic/pernicious anemia
-immature RBC released into circulation

B12 deficiency only is associated with demyelination and degeneration of spinal cord

this is part of the folate trap

36

what is transcobalamine?

protein that transports B12 in body (less commonly a problem)

37

what is the folate trap?

when B12 is deficiency, it traps folate in N5 methyl form, and manifests as anemia
-if folate is supplemented, it is never deficient, thus causes B12 deficiency and irreversible neurological problems without anemia

38

what does deficiency in cystathionine beta-synthetase do?

homocystinuria (cannot convert HC to cystathionine)
-children die by age 3-4 from heart disease or stroke (high atherosclerosis)

39

what does deficiency in gamma-cystathionase do?

cystathionuria (cannot convert cystathionine to cysteine)
-die of atherosclerosis at not-child age

40

what AA need B12 to degrade carbon skeletons?

valine, isoleucine and methionine