nucleotide metabolism

Question 1

purines: where do carbons come from?

Answer 1

9 carbons from amino acids, 1 from CO2

Question 2

purine synthesis overview

Answer 2

IMP is made then converted to purines

Question 3

purine synthesis step 1

Answer 3

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

Question 4

purine synthesis step 2

Answer 4

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!

Question 5

purine synthesis step 3

Answer 5

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

Question 6

purine synthesis step 4

Answer 6

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

Question 7

purine synthesis 5

Answer 7

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

Question 8

purine synthesis 6

Answer 8

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

Question 9

after AIR

Answer 9

Eventually get to IMP

undergoes cyclization, glutamine donate, and carboxylation, releases fumarate

Question 10

N1
N3
N7
N9

Answer 10

aspartate
glutamine
glycine
glutamine

Question 11

C2
C4
C5
C8

Answer 11

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

Question 12

After IMP

Answer 12

1) IMP to AMP

2) IMP to GMP

Question 13

IMP to AMP

Answer 13

uses aspartate
releases fumarate
uses GTP

Question 14

IMP to GMP

Answer 14

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

Question 15

NADH from GMP synthesis

Answer 15

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

Question 16

glutamine is a great…

Answer 16

amino donor

Question 17

high ADP

Answer 17

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

Question 18

high adenine or guanine (purines)

Answer 18

decreases activity of Gln-PRPP aminotransferase

Question 19

high PRPP

Answer 19

activates Gln-PRPP aminotransferase

Question 20

control at branch point

Answer 20

determines whether we get ATP or GTP

important because we need right ratio of nucleotides to decrease mutations

Question 21

high AMP

Answer 21

blocks adenylosuccinate synthetase

Question 22

high GMP

Answer 22

blocks IMP dehydrogenase

Question 23

when is purine synthesis high?

Answer 23

when cells are about to divide

RBC don’t synthesize purines

Question 24

PRPP synthesis regulation

Answer 24

inhibited by ADP and GDP

Question 25

Gln-PRPP amidotransferase regulation

Answer 25

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

Question 26

purine synthesis is balanced

Answer 26

1) GMP and AMP slow their own production | 2) GTP and ATP facilitate the synthesis of the opposite purine

Question 27

pyrimidine: where do carbons come from

Answer 27

4/6 carbons from aspartate

Question 28

C2 | N3

Answer 28

Carbamoyl-P

Question 29

N1 C4 C5 C6

Answer 29

Aspartate

Question 30

where is CPS2?

Answer 30

in the cytoplasm

Question 31

carbamoyl phosphate rxns (step 1 of pyrimidine synthesis)

Answer 31

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

Question 32

pyrimidine synthesis step 2

Answer 32

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

Question 33

pyrimidine synthesis step 3

Answer 33

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

Question 34

dihydroorotase is part of...

Answer 34

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

Question 35

pyrimidine synthesis step 4

Answer 35

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

Question 36

pyrimidine synthesis step 5

Answer 36

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

Question 37

OMP and ribosyl transferase are...

Answer 37

coupled enzymes!

Question 38

pyrimidine synthesis step 6

Answer 38

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

Question 39

UMP to UTP

Answer 39

UMP --> UDP --> UTP | uses ATP

Question 40

UTP to CTP

Answer 40

CTP synthetase | uses glutamine + ATP + H2O to glutamate + ADP + P

Question 41

which enzyme catalyzes committed step of pyrimidine synthesis?

Answer 41

CPS-II

Question 42

CPS-II control

Answer 42

UDP and UTP feedback inhibit | PRPP and ATP allosterically activate

Question 43

deoxyribonucleotide synthesis

Answer 43

``` 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 ```

Question 44

ribonucleotide reductase

Answer 44

deals with nucleotides | ultimate reducing power comes from NADPH

Question 45

regulation of dNTP synthesis before S phase of cell cycle

Answer 45

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

Question 46

nucleotide catabolism and salvage

Answer 46

salvage of bases allows reuse of bases

Question 47

glutamine analogs

Answer 47

irreversibly inhibit glutamine dependent enzymes

Question 48

folate analogs

Answer 48

block synthesis of THF

Question 49

some drugs block

Answer 49

cancer, fungal infections, and malaria

Question 50

FdUMP

Answer 50

a suicide inhibitor

Question 51

purine analogs

Answer 51

inhibit purine synthesis