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
Q

How does most nucleic acid degredation take place in cells?

A

nucleic acid degredation: normal process of nucleic acid turn over INSTEAD OF using nucleotides from diet

26
Q

review slide 10

A

review slide 10

27
Q

all nitrogens in the bases come from…

A

amino acids

pyramides nitrogens: largely come from aspartate

28
Q

Why are pyrimidine and pure biosynth different?

A

purine bases are built directly onto ribose sugars

pyramidine bases built first then put on ribose sugar

29
Q

significant things about purine biosynth

A

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
Q

base shown in slide 12 is IMP: what is it a precursor to?

A

AMP and GMP

31
Q

How to get IMP AMP and GMP

A

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
Q

why use ATP to make GMP and use GTP to make AMP?

A

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
Q

regulation of purine biosynth

A

regulated at multiple steps

product feedback regulates the enzymes

34
Q

ATP is used as a substrate in GMP biosynth. GTP is used as a substrate in AMP biosynth. What does this achieve

A

balance of ATP and GTP production

35
Q

Purine degredation

A

convert to uric acid and excrete

36
Q

AMP degredation

A

deaminated by AMP deaminase… makes IMP
IMP dephosphorylated= isosine (I)
purine nucleoside phosphorylase=free base (hypoxanthine)
base (hypoxanthine) oxidized to make uric acid

37
Q

uric acid excretion

A

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
Q

Gout

A

defect in purine metabolism
uric acid build-up in joints
treat by allopurinol to inhibit xanthine oxidase

39
Q

What causes Lesch-Nyhan disease and SCID?

A

defects in enzyme HGPRT and ADA respectively

also result in gout

40
Q

Lesch-Nyhan disease

A

severe nuerological disorders and gout

due to uric acid build up on body

41
Q

pyrimidine biosynth

A

first make base (orotate), then link it to ribose-5P to make UMP

42
Q

UMP

A

common uncleotide.

convert it to UTP, then CTP

43
Q

Regulation of pyrimidine biosynth: bacteria

A

1 enzyme (ATCase)
inhibited by CTP
stimulated by ATP (cells ready to divide)

44
Q

Regulation of pyrimidine biosynth: animal cells

A

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
Q

Ribonucleotide reductase

A

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
Q

to regenerate Ribonucleotide reductase after reducing its sulfied bond

A

reduce it with thioredoxin

47
Q

How does thioredoxin get re reduced?

A

picks up hydrogen atoms from enzyme thioredoxin reductase (contains FAD and oxidizes NADPH)

48
Q

Regulation of Ribonucleotide reductase

A

2 regulatory sites:
regulatory site
substrate specificity site

49
Q

Ribonucleotide reductase: REGULATORY SITE

A

ATP or dATP binds here

controls overall enzyme activity

50
Q

Ribonucleotide reductase: SUBSTRATE SPECIFICITY SITE

A

choose which substrates to bind and do reactions on

ATP, dATP, dTTP, dGTP bind here

51
Q

synthesis of thymine containing nucleotides (so only DNA)

A

3 ways:

1: dephosphorylate dUTP–>dUMP
2. deaminate dCTP to make dUTP, then to dUMP
3. phosphorylate deoxyuridien to get dUMP

52
Q

Why go to dUMP?

A

this leads down a pathway to make dTTP, which we can use in DNA synth

53
Q

why don’t we want much dUTP???

A

its not incorporated into DNA, it has URIADINE!!! (U is just for RNA)

54
Q

RNA World Hypothesis

A

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