Lecture 25: Nucleotide Metabolism Flashcards

1
Q

purine bases

A

adenine
guanine
attachment for sugar is at N9 position (9 atoms in ring)

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2
Q

pyramidine bases

A

cytosine
uracil
thymine
sugar attached at N1 position (6 atoms in ring)

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3
Q

bases can be salvaged or resued (T or F)

A

TRUE

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4
Q

nucleotide structure

A

base
ribose sugar
1, 2, or 3 phosphate groups

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5
Q

nucleotide functions

A

building blocks of DNA and RNA
energy currency
components of coenzymes
signal transduction

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6
Q

where do the nitrogens for the bases come from

A

amino acids

glycine, aspartate, glutamate

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7
Q

where do ribose sugars come from?

A

PPP!

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8
Q

what happens when bases are degraded?

A
uric acid (purine degredation)
pyramidine catabolism= lots of metabolites, like NH4+
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9
Q

phosphates named…

A
alpha
beta
gamma
in order
carbons in sugar get primes as well as number
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10
Q

nucleoside

A

just sugar and base

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11
Q

Whats at the 2’ carbon in a deoxyribose sugar (DNA)?

A

no hydroxyl group

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12
Q

Whats at the 2’ carbon in a ribose sugar (RNA)?

A

hydroxyl group

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13
Q

what does having/not having a hydroxyl group mean

A

stability difference
having a hydroxyl group makes it more unstable: can undergo cleavage reaction :O
so RNA is less stable than DNA
thats why we dont store genetic material in RNA

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14
Q

Nucleotide 4 major functions”

A

nrg currency: ATP
second messengers: cAMP
coenzymes: NAD+
build RNA and DNA

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15
Q

What base is in all: ATP, cAMP, NAD+, DNA, RNA

A

ADENINE!!!!

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16
Q

How do the two strands of DNA interact?

A

non covalent interactions between bases

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17
Q

Direction of DNA strand:

A

5’ to 3’

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18
Q

How are nucleotides in a SINGLE strand linked?

A

covalently linked
phosphodiester bonds
connect C3’ to C5’

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19
Q

What bases pair?

A

TA
GC
UA

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20
Q

Coenzyme A

A

has an adenine base!!!

thats what the A stands for

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21
Q

examples of coenzymes with adenine

A

NADP, NAD, FAD, coA

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22
Q

Salvage pathway for nucleotide components: used for RNA synth

A

put in triphosphate form to get triphosphate (use kinases)
synth RNA
enzymes used are polymerases

23
Q

RNA degredation

A

endonucleases break it down
left w/ oligonucleotides: short pieces of RNA
phosphodiesterases break phosphodiesterase bonds: release single nucleotide

24
Q

Changing attachment: attach a different base

A

remove phosphate group: just sugar and base
then remove base: left w/ ribose 1 phosphate
move the ribose so now its ribose 5 phosphate
PRPP puts pyrophophate group at 1’
attach a base
bam! New nucleotide

25
How does most nucleic acid degredation take place in cells?
nucleic acid degredation: normal process of nucleic acid turn over INSTEAD OF using nucleotides from diet
26
review slide 10
review slide 10
27
all nitrogens in the bases come from...
amino acids | pyramides nitrogens: largely come from aspartate
28
Why are pyrimidine and pure biosynth different?
purine bases are built directly onto ribose sugars | pyramidine bases built first then put on ribose sugar
29
significant things about purine biosynth
start with the sugar use lots of enzymes: PRPP synthtase uses ATP to make PRPP at 1' position base building has begun (with attaching a nitrogen) lots of energy invested: directly takes 5 ATP SEE SLIDE 12
30
base shown in slide 12 is IMP: what is it a precursor to?
AMP and GMP
31
How to get IMP AMP and GMP
3 paths 1. use nitrogen from aspartate, use GTP hydrolysis, lose fumerate, adenine is attached: form AMP 2. put an oxygen on I. using NADH. Use ATP to take nitrogen from glutamine. Get GMP
32
why use ATP to make GMP and use GTP to make AMP?
You don't want to use the nucleotide you're trying to make! | You can't have a step that would be dependent on what you're trying to make! that would be dumb.
33
regulation of purine biosynth
regulated at multiple steps | product feedback regulates the enzymes
34
ATP is used as a substrate in GMP biosynth. GTP is used as a substrate in AMP biosynth. What does this achieve
balance of ATP and GTP production
35
Purine degredation
convert to uric acid and excrete
36
AMP degredation
deaminated by AMP deaminase... makes IMP IMP dephosphorylated= isosine (I) purine nucleoside phosphorylase=free base (hypoxanthine) base (hypoxanthine) oxidized to make uric acid
37
uric acid excretion
break down of purines by primates, some insects etc NOT A WAY TO GET RID OF EXTRA NITROGEN because nitrogen excretion through urea needs more water JUST AS A BREAKDOWN OF PURINES!!!!!!!!
38
Gout
defect in purine metabolism uric acid build-up in joints treat by allopurinol to inhibit xanthine oxidase
39
What causes Lesch-Nyhan disease and SCID?
defects in enzyme HGPRT and ADA respectively | also result in gout
40
Lesch-Nyhan disease
severe nuerological disorders and gout | due to uric acid build up on body
41
pyrimidine biosynth
first make base (orotate), then link it to ribose-5P to make UMP
42
UMP
common uncleotide. | convert it to UTP, then CTP
43
Regulation of pyrimidine biosynth: bacteria
1 enzyme (ATCase) inhibited by CTP stimulated by ATP (cells ready to divide)
44
Regulation of pyrimidine biosynth: animal cells
inhibition from products of inidividual steps reactions stimulated by PRPP and ATP (cells are ready to divide, so we need to make more ATP and DNA)
45
Ribonucleotide reductase
converts ribonucleotides to deoxyribonucleotides reduce C-2', remove the hydroxyl group! (now enzyme is oxidized) reduce enzyme sulfide bond so basically (after next two slides) the electrons come from NADPH
46
to regenerate Ribonucleotide reductase after reducing its sulfied bond
reduce it with thioredoxin
47
How does thioredoxin get re reduced?
picks up hydrogen atoms from enzyme thioredoxin reductase (contains FAD and oxidizes NADPH)
48
Regulation of Ribonucleotide reductase
2 regulatory sites: regulatory site substrate specificity site
49
Ribonucleotide reductase: REGULATORY SITE
ATP or dATP binds here | controls overall enzyme activity
50
Ribonucleotide reductase: SUBSTRATE SPECIFICITY SITE
choose which substrates to bind and do reactions on | ATP, dATP, dTTP, dGTP bind here
51
synthesis of thymine containing nucleotides (so only DNA)
3 ways: 1: dephosphorylate dUTP-->dUMP 2. deaminate dCTP to make dUTP, then to dUMP 3. phosphorylate deoxyuridien to get dUMP
52
Why go to dUMP?
this leads down a pathway to make dTTP, which we can use in DNA synth
53
why don't we want much dUTP???
its not incorporated into DNA, it has URIADINE!!! (U is just for RNA)
54
RNA World Hypothesis
it can both carry genetic stuff and do enzyme stuff it had its own thing to catalyze: RIBOZYMES then Ribonucleotide reductase (an enzyme made of PROTEINS) emerged, and DNA made more sense