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Biochemistry 2 > nucleotide metabolism > Flashcards

nucleotide metabolism Flashcards

1
Q

purines: where do carbons come from?

A

9 carbons from amino acids, 1 from CO2

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2
Q

purine synthesis overview

A

IMP is made then converted to purines

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3
Q

purine synthesis step 1

A

ribose-5-phosphate (from PPP) to PRPP synthesis
Enzyme: ribose-5-phosphate pyrophosphokinase
ATP to AMP
This step is used to make all nucleotides, NOT COMMITTED to purines yet

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4
Q

purine synthesis step 2

A 
PRPP to phosphoribosyl-beta-amine
Enzyme: Gln: PRPP amido-transferase
Glutamine + H2O to glutamate + PP
PP (pyrophosphate is released and immediately degraded)
Committed to purines!
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5
Q

purine synthesis step 3

A

phosphoribosyl-beta-amine to GAR
Enzyme: GAR synthetase
Glycine + ATP to ADP + P
We added glycine

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6
Q

purine synthesis step 4

A

GAR to FGAR
Enzyme: GAR transformylase
N10-formyl-THF to THF
The first use of THF!

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7
Q

purine synthesis 5

A

FGAR to FGAM
Enzyme: FGAM synthetase
ATP + Glutamine + H2O to ADP + Glutamate + P
Glutamine donates amine groups again!

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8
Q

purine synthesis 6

A

FGAM to AIR
Enzyme: AIR synthetase
ATP to ADP + P
Cyclize!

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9
Q

after AIR

A

Eventually get to IMP

undergoes cyclization, glutamine donate, and carboxylation, releases fumarate

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10
Q

N1
N3
N7
N9

A

aspartate
glutamine
glycine
glutamine

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11
Q

C2
C4
C5
C8

A

N10-formyl-THF
Glycine
Glycine
N10-formyl-THF

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12
Q

After IMP

A

1) IMP to AMP

2) IMP to GMP

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13
Q

IMP to AMP

A

uses aspartate
releases fumarate
uses GTP

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14
Q

IMP to GMP

A

IMP to XMP to GMP
uses NAD+ to NADH
uses glutamine + ATP to glutamate + ADP + PP

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15
Q

NADH from GMP synthesis

A

NADH is acquired energy → can contribute to ATP production in ETC

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16
Q

glutamine is a great…

A

amino donor

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17
Q

high ADP

A

low energy
cells won’t make new nucleotides
decrease ribose-5-phosphate pyrophosphokinase

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18
Q

high adenine or guanine (purines)

A

decreases activity of Gln-PRPP aminotransferase

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19
Q

high PRPP

A

activates Gln-PRPP aminotransferase

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20
Q

control at branch point

A

determines whether we get ATP or GTP

important because we need right ratio of nucleotides to decrease mutations

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21
Q

high AMP

A

blocks adenylosuccinate synthetase

22
Q

high GMP

A

blocks IMP dehydrogenase

23
Q

when is purine synthesis high?

A

when cells are about to divide

RBC don’t synthesize purines

24
Q

PRPP synthesis regulation

A

inhibited by ADP and GDP

25
Q

Gln-PRPP amidotransferase regulation

A

activated by PRPP

inhibited by AMP, ADP, and ATP at one regulatory site and GMP, GDP, and GTP at the other

26
Q

purine synthesis is balanced

A

1) GMP and AMP slow their own production

2) GTP and ATP facilitate the synthesis of the opposite purine

27
Q

pyrimidine: where do carbons come from

A

4/6 carbons from aspartate

28
Q

C2

N3

A

Carbamoyl-P

29
Q

N1
C4
C5
C6

A

Aspartate

30
Q

where is CPS2?

A

in the cytoplasm

31
Q

carbamoyl phosphate rxns (step 1 of pyrimidine synthesis)

A

1) bicarbonate to carboxy phosphate
2) carboxy phosphate + Gln to Carbamate + Glu
3) carbamate to carbamoyl-P (CP)

32
Q

pyrimidine synthesis step 2

A

carbamoyl-P to Carbamoyl-Asp
Enzyme: ATCase
Aspartate to P

33
Q

pyrimidine synthesis step 3

A

carbamoyl-Asp to DHO
Enzyme: dihydroorotase
Release OH-
Close the ring!

34
Q

dihydroorotase is part of…

A

Enzyme is part of a multifunctional polypeptide chain including CPSII and aspartate transcarbamoylase
Metabolic channeling between diff activities → coordinated production of pyrimidines

35
Q

pyrimidine synthesis step 4

A

DHO to orotate (a pyrimidine)
Enzyme: DHO dehydrogenase
Coenzyme Q to coenzyme QH2 (in outer mitochondrial membrane)
Add a double bond!

36
Q

pyrimidine synthesis step 5

A

Orotate to OMP
Enzyme: orotate phosphoribosyltransferase
alpha-PRPP to PP
Add ribose!

37
Q

OMP and ribosyl transferase are…

A

coupled enzymes!

38
Q

pyrimidine synthesis step 6

A

OMP to UMP
Enzyme: OMP decarboxylase
Release CO2
*From UMP, you can make any other pyrimidine

39
Q

UMP to UTP

A

UMP –> UDP –> UTP

uses ATP

40
Q

UTP to CTP

A

CTP synthetase

uses glutamine + ATP + H2O to glutamate + ADP + P

41
Q

which enzyme catalyzes committed step of pyrimidine synthesis?

A

CPS-II

42
Q

CPS-II control

A

UDP and UTP feedback inhibit

PRPP and ATP allosterically activate

43
Q

deoxyribonucleotide synthesis

A 
NDP to dNDP
N = A, G, C, U
enzyme: ribonucleotide reductase
H to OH
2SH to SS cysteine residues (puts reducing power back into the enzyme)
enzyme becomes oxidized
44
Q

ribonucleotide reductase

A

deals with nucleotides

ultimate reducing power comes from NADPH

45
Q

regulation of dNTP synthesis before S phase of cell cycle

A

1) increasing level of synthetic enzymes = increase general purine and pyrimidine synthesis
2) express ribonucleotide reductase
3) express thymidylate synthase
4) express TMP kinase

46
Q

nucleotide catabolism and salvage

A

salvage of bases allows reuse of bases

47
Q

glutamine analogs

A

irreversibly inhibit glutamine dependent enzymes

48
Q

folate analogs

A

block synthesis of THF

49
Q

some drugs block

A

cancer, fungal infections, and malaria

50
Q

FdUMP

A

a suicide inhibitor

51
Q

purine analogs

A

inhibit purine synthesis

Biochemistry 2 (32 decks)

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