Nucleotide Metabolism

Question 1

Nucleoside

Answer 1

Nitrogen-containing ring compounds linked to a 5-carbon sugar (ribose/deoxyribose)

Question 2

Nucleotide

Answer 2

A nucleotide consists of a nitrogen-containing

base, a five-carbon sugar, and one or more

phosphate groups. (Nucleoside + P)

Question 3

Purine base

Answer 3

five-membered ring fused to the six-membered ring

(Guanine & Adenine)

Question 4

Pyrimidine Base

Answer 4

Six-membered ring

Cytosine (C), thymine (T), and uracil (U)

Question 5

RNA

Answer 5

• Single stranded
• OH on 2’ position of the ribose carbon ring
• A,G,C,U
• more transient carrier of molecular instructions

Question 6

DNA

Answer 6

• H on 2’ position of the ribose carbon ring
• A,G,C,T
• double stranded ( held together by H bonds)
• Long term repository for heredity information

Question 7

Nucleotide Functions

Answer 7

• They carry chemical energy in their easily hydrolyzed phosphoanhydride bonds.
• They combine with other groups to form coenzymes.
• They are used as small intracellular signaling molecules in the cell.

Question 8

What molecule is PRPP derived from, and what pathway generates this molecule?

Answer 8

• PRPP is derived from the ribose-5 phosphate that is generated by the pentose phosphate pathway.

Question 9

What purine is made first by the de novo pathway for purine synthesis?

Answer 9

• The purine inosine monophosphate (IMP) is formed first, it is then converted to either adenosine monophosphate (AMP) or guanosine monophosphate (GMP)

Question 10

What enzyme is needed for synthesis of GMP by the purine salvage pathway?

Answer 10

enzyme HGPRT is needed for GTP synthesis

Question 11

What enzyme is required for de novo synthesis of purines?

Answer 11

amido PRT, this enzyme catalyzes the conversion of PRPP and glutamine to purine nucleotides.

Question 12

What pyrimidine is formed first in the pyrimdine de novo synthesis pathway

Answer 12

orotate monophosphate (OMP) is the first pyrimidine based formed

Question 13

Is PRPP needed for pyrimidine synthesis?

Answer 13

Yes

Question 14

What are the 2 products of the first step of degradation of purines?

Answer 14

hypoxanthine and xanthine

Question 15

What is the end product of purine degradation?

Answer 15

Uric Acid

Question 16

What is the end product of uracil degradation?

Answer 16

acetyl CoA

Question 17

What is the end product of thymidine degradation?

Answer 17

Succinyl CoA

Question 18

Roles of ribonucleotides :

Answer 18

• building blocks for RNA
• ATP
• intracellular signaling molecules (cAMP)

Question 19

Degradation of purine generates ____

Answer 19

Uric Acid

Question 20

catalyzed by ribonucletide reductase ( this is a drug target)

Answer 20

UMP, AMP, GMP, CMP ribonuc. ——> Deoxyribonuc.

Question 21

Thymidylate synthase

Answer 21

• catalyzed the conversion of TMP is generated from UMP
• This conversion requires THF

Question 22

Dihydrofolate Reductase

Answer 22

• is a Drug Target
• Required for synthesis of THF
• inhibition will leat to dTMP cannot be made

Question 23

Degradation of pyrimidine nucleotides generates ____

Answer 23

intermediates that can be further metabolized and enter the TCA cycle

Question 24

Pyrimidine metabolism

De novo synthesis

Answer 24

• Orotate is the first base formed
• Orotate is then joined to PRPP to form orotate monophosphate (OMP)
• OMP is then used to synthesize all other pyrimidine nucleotides

Question 25

Pyrimidine metabolism

Salvage;

Answer 25

• Uracil or orotate (pyrimidine bases) + PRPP = pyrimidine nucleoside monophosphate (i.e. UMP or CMP)
• catalyzed by UPRT and OPRT
• end product is acetyl coA and succinyl coA

Question 26

Elimination of uric acid from the body

Answer 26

• Uric acid is eliminated by the kidney (65%)

and via the GI tract (35%)

• Approximately 90% of filtered uric acid is

reabsorbed via urate transporter 1 (URAT1)

• URAT1 polymorphisms may predispose

patients to gout (= increased uric acid

reabsorption = increased uric acid plasma

levels)

Question 27

HGPRT

Answer 27

an enzyme that is associated with the purine salvage pathways – it is needed to generate GMP and IMP (guanine and hypoxanthine are substrates, respectively)

Question 28

APRT

Answer 28

enzyme that is associated with the purine salvage pathway – it is needed to generate AMP (substrate is adenine)

Question 29

Decreased activity of the salvage pathway leads to ____

Answer 29

increased activity of the de novo pathway

Question 30

Genetic deficiencies of HGPRT (salvage pathway enzyme)

Answer 30

• eventually leads to increased in uric acid –> hyperucemia
• purine bases are not salvaged and are degraded to uric acid… = increased uric acid levels (also, decreased activity of the purine salvage pathway causes increased activity of the purine de novo pathway)

Question 31

Excess of PRPP

Answer 31

increases purine de novo pathway

because PRPP activates amido PRT

Question 32

Purine metabolism;

De novo synthesis

Answer 32

the first purine nucleotide made via de novo synthesis is IMP. IMP can then be converted to all other purine nucleotidesamido PRT is a regulated enzyme

Question 33

Purine Salvage pathway;

Answer 33

Hypoxanthine + PRPP⇒ IMP + Ppi, catalyzed by HGPRT

Guanine + PRPP ⇒ GMP + Ppi, catalyzed by HGPRT

Adenine + PRPP ⇒ AMP + Ppi, catalyzed by APRT

Question 34

Amido PRT

Answer 34

(amido phosphoribosyltransferase) is the regulated step for IMP synthesis; it is positively regulated by PRPP and negatively regulated by purine nucleotides