Nucleotide Synthesis and Degradation

Question 1

3 amino acids needed for making a purine

Answer 1

Gly
Gln
Asp

Question 2

Starting material for purine synthesis

Answer 2

Ribose-6-phosphate

Question 3

First step in Purine synthesis

Answer 3

Ribose 5-phopshate —-> PRPP

via-Ribose-5-pyrophosphokinase

Question 4

Ribose-5-pyrophosphokinase does what?

Answer 4

Adds 2 phosphates to R5P to make PRPP

Question 5

PRPP , once generated .. does what

Answer 5

Goes to Phosphoribosyl-Beta amine (via-Gln:PRPP amidotransferase)

Question 6

What step is fumarate generated in ?

Answer 6

SAICAR——–> AICAR (Adenylosuccinate lyase)

Question 7

Purine synthesis requires

Answer 7

R5P (from PPP)

Gln
Glycogen
Asp

7 ATP eqivalents

THF

Question 8

Key products of PPP

Answer 8

NADPH and R5P

Question 9

3 step generation of R5P

Answer 9

Glucose-6-phosphate –1.——-> 6-phosphogluconate—-2—> R5P

1. G6P dehydrogenase
2. Phosphogluconate dehydrogenase

These 2 enzymes use NADP

Question 10

Types of enzymes discussed that require TPP

Answer 10

Dehydrogenases and transketolase

Question 11

Only certain adult cells need to have high rates of nucleic acid synthesis , so what can happen ?

Answer 11

R5P can go back and form glycolytic intermediates such as F6P and G3P

Question 12

Inborn error of metabolism commonly occurs for

Answer 12

G6P dehydrogenase

Question 13

G6P dehydrogenase deficiency leads to

Answer 13

low NADPH , but R5P levels are normal due to reversible reactions.

Question 14

Low NADPH can inhibit the boys ability to

Answer 14

defend off oxidative stress

Question 15

Enzyme that uses NADPH to make sure that sulfide groups remain in the correct oxidative state

Answer 15

Glutathione reductase

Question 16

To get from Folate to THF , the reactions must use

Answer 16

NADPH

Question 17

Fates of IMP

Answer 17

1. AMP (Adenylosuccinate synthase) (Generates fumarate)
2. GMP (IMP dehydrogenase) (uses Gln)

both products act as allosteric inhibitors

Question 18

Activators and inhibitors of purine synthesis

Answer 18

Inhibitors : AMP, ADP , ATP

Activators: alpha PRPP-its the substrate that says , keep up

Question 19

Nucleotides are converted to nucleosides by

Answer 19

nucleotidases

Question 20

Nucleosides are degraded by

Answer 20

Purine nucleoside phosphorylase (PNP)

Question 21

Guanine is converted to Xanthine by

Answer 21

guanine deaminase

Question 22

Precursor of HYpoanthine

Answer 22

Inosine

Converted to hypoxanthine by (Purine nucleoside phosphorylase)

Question 23

Hypoxanthine is oxidized by

Answer 23

XO in the liver, intestines,

to uric acid

Question 24

Enzyme that converts AMP to IMP

Answer 24

AMP deaminase

Question 25

First product made from R5P

Answer 25

alpha PRPP

Question 26

Tell me about HGPRT enzyme

Answer 26

Hypoxanthine-guanine phosphoribosyltransferase

This enzyme allows hypoxanthine and guanine to go to IMP and GMP

Question 27

Lesch Nyhan Syndrome

Answer 27

Complete deficiency of HGPRT

-This leads to a deficiency in purines , now you have a flood of purine catabolism to uric acid. Also have a deficiency in nucleotides so you can have neurocognitive effects.

Question 28

SCIDS

Answer 28

Lack the enzyme
-Adenosine Deaminase

This does not allow conversion of deoxyadenosine to deoxyinosine.

If you can’t make the deoxunucleotides, then you can’t perform DNA replication. Immune cells cannot proliferate and have to live in a sterile environment.

Question 29

Two things needed for Pyrimidine synthesis

Answer 29

Carbamoyl Phosphate synthetase 2 and aspartate

CPSII and Asp

Question 30

Committed step in pyrimidine synthesis

Answer 30

CPSII

Question 31

Pyrimidine synthesis requires

Answer 31

4 ATP equivalents
2 Amino acids
Coenzyme Q
Bicarb

Question 32

First step in pyrimidine synthesis

Answer 32

Bicarb + Gln +2ATP +Water ——> Carbamoyl-Phosphate

via-CPS-II

Question 33

In pyrimidine synthesis , where is alpha PRPP used ?

Answer 33

Orotate——>Orotidine 5’-monophosphate

(via-Orate phosphoribosyltransferase. This is where alpha PRPP is used).

Question 34

UMP to CTP

Answer 34

CTP synthase -this is the enzyme.

Question 35

Regulation of Pyrimidine synthesis

Answer 35

UDP and UTP-“we have enough , STOP!”

ATP-“Hey, I’m a purine, lets crank out some pyrimidines too!

PRPP-“hey, lots of Ribose-5-phopshate around, Lets make some pyrimidines baby.”!!!

Question 36

Orotic Aciduria

Answer 36

Deficiency in OMP

orotate phosphoribosyltransferase

inhibits UMP synthesis

Increased orotic acid in urine , megaloblastic anemia , mental and physical development , failure to thrive,

Treatment is oral uridine administration

Question 37

Regulation of deoxyribonucleotide synthesis

Answer 37

ATP-“Lots of us, we now have enough to make the deoxy”

dATP-we have enough

Question 38

Deoxyribonucleotide synthesis

Answer 38

NDP—————->dNDP

via( Ribonucleotide reductase) Always reduces the di nucleotide

Question 39

dUMP to dTMP

Answer 39

Thymidylate synthase

Question 40

Folic acid is needed to make what regarding pyrimidine synthesis

Answer 40

dTMP which then goes to dTDP then to dTTP

Question 41

Folic acid analogue that inhibits DHFR and therefore the synthesis of THF needed for purine nucleotide, thymidylate, serine, and methionine synthesis.

Answer 41

Methotrexate

Question 42

Converted to ara-CTP (cytosine arabinoside triphosphate) which competes with DNA polymerase alpha thereby resulting in blockade of DNA synthesis.

Answer 42

Cytarabine.

Question 43

Inhibits DNA synthesis. Converted to active metabolite that inhibits thymidylate synthase and therefore thymidylate synthesis.

Answer 43

5-fluorouracil

Question 44

Fluorine substituted deoxycytidine analog that inhibits DNA synthesis . Active metabolite inhibits ribonucleotide reductase needed for pyrimidine synthesis.

Answer 44

Gemcitabine