T8. NUCLEOTIDE METABOLISM

Question 1

What is a nucleoside?

Answer 1

A nitrogen base linked to a pentose sugar (ribose or deoxyribose).

Question 2

What is a nucleotide?

Answer 2

A nucleoside bound to one 3P

Question 3

What are the two types of nitrogenous bases?

Answer 3

1. Purines – Adenine (A) and Guanine (G); have a double-ring structure.
2. Pyrimidines – Cytosine (C), Thymine (T), and Uracil (U); have a single-ring structure.

Question 4

What are the metabolic functions of nucleotides?

Answer 4

Nucleic acid synthesis

Question 5

What are the two nucleotide synthesis pathways?

Answer 5

De novo synthesis and recovery (salvage) pathway.

Question 6

What is the de novo synthesis pathway?

Answer 6

Synthesis of purine/pyrimidine nucleotides from small precursors; energy-intensive; all organisms use it.

Question 7

What is the recovery pathway?

Answer 7

Synthesizes nucleotides from preexisting bases/nucleotides via diet or nucleic acid catabolism; maintains nucleotide pool balance.

Question 8

What is the first step in purine de novo synthesis?

Answer 8

Ribose-5-phosphate is converted to PRPP by PRPP synthase using 1 ATP.

Question 9

What enzyme uses PRPP and glutamine to begin purine synthesis?

Answer 9

Glutamine-PRPP-aminotransferase (rate-limiting enzyme).

Question 10

What is the first purine nucleotide synthesized in de novo synthesis?

Answer 10

Inosine monophosphate (IMP).

Question 11

What are the requirements to synthesize IMP?

Answer 11

5 ATP

Question 12

How is the purine ring formed in IMP synthesis?

Answer 12

Through stepwise addition of atoms from glutamine

Question 13

What does IMP become?

Answer 13

It can be converted to AMP via adenylsuccinate synthase or to GMP via IMP dehydrogenase.

Question 14

How is glutamine-PRPP amidotransferase regulated?

Answer 14

Positively by PRPP and ATP; negatively by AMP and GMP (allosteric regulation).

Question 15

What is competitive regulation in purine synthesis?

Answer 15

AMP inhibits adenylsuccinate synthase; GMP inhibits IMP dehydrogenase.

Question 16

What is coordinated synthesis in purine metabolism?

Answer 16

ATP drives GMP synthesis; GTP drives AMP synthesis for balance.

Question 17

What is the purpose of the purine salvage pathway?

Answer 17

Recycles purine bases into nucleotides

Question 18

What enzymes are involved in the phosphoribosyl transferase salvage pathway?

Answer 18

HGPRT (hypoxanthine and guanine) and APRT (adenine).

Question 19

What are the reactions catalyzed by phosphoribosyl transferases?

Answer 19

Hypoxanthine + PRPP → IMP; Guanine + PRPP → GMP; Adenine + PRPP → AMP.

Question 20

What does adenosine kinase do?

Answer 20

Converts adenosine + ATP → AMP + ADP.

Question 21

What is the precursor molecule in de novo pyrimidine synthesis?

Answer 21

UMP (uridine monophosphate).

Question 22

What is the main difference between purine and pyrimidine synthesis?

Answer 22

Purine ring is built on PRPP; pyrimidine ring is built first

Question 23

What is the first step in pyrimidine synthesis?

Answer 23

CPS-II catalyzes formation of carbamoyl phosphate from bicarbonate and NH₃ using 2 ATP (rate-limiting step).

Question 24

Where does CPS-II function?

Answer 24

In the cytosol (unlike CPS-I which functions in mitochondria for urea cycle).

Question 25

What happens after carbamoyl phosphate is formed in pyrimidine synthesis?

Answer 25

It reacts with aspartate via aspartate transcarbamylase to form the ring structure.

Question 26

What happens after the pyrimidine ring is formed?

Answer 26

PRPP binds to the ring to form UMP

Question 27

What is UMP a precursor of?

Answer 27

CMP and TMP.

Question 28

What is the first step in UMP synthesis?

Answer 28

Glutamine is converted to carbamoyl phosphate by CPS-II using 2 ATPs and bicarbonate.

Question 29

What enzyme catalyzes the synthesis of carbamoyl phosphate?

Answer 29

Carbamoyl phosphate synthase II (CPS-II).

Question 30

What substrates are required to form carbamoyl phosphate in UMP synthesis?

Answer 30

Glutamine

Question 31

What is the next step after forming carbamoyl phosphate in UMP synthesis?

Answer 31

Aspartate is introduced to form carbamoyl aspartate.

Question 32

What does carbamoyl aspartate become in UMP synthesis?

Answer 32

It is converted into dihydroorotate.

Question 33

What happens to dihydroorotate in UMP synthesis?

Answer 33

It is oxidized to orotic acid.

Question 34

What does orotic acid bind to during UMP synthesis?

Answer 34

A ribose to form orotidine monophosphate (OMP).

Question 35

What is OMP converted into?

Answer 35

UMP

Question 36

What are the requirements for UMP synthesis?

Answer 36

2 ATP

Question 37

How is CTP synthesized?

Answer 37

From UTP via CTP synthetase.

Question 38

What is required for CTP synthesis?

Answer 38

ATP and ammonium from glutamine.

Question 39

What is the regulatory step of pyrimidine synthesis?

Answer 39

The condensation of bicarbonate and glutamine to form carbamoyl phosphate.

Question 40

What enzyme catalyzes the regulatory step of pyrimidine synthesis?

Answer 40

Carbamoyl phosphate synthase II (CPS-II).

Question 41

What type of regulation controls CPS-II?

Answer 41

Feedback inhibition.

Question 42

What activates CPS-II?

Answer 42

PRPP and ATP.

Question 43

What inhibits CPS-II?

Answer 43

UDP and UTP.

Question 44

Which step in pyrimidine synthesis is also regulated?

Answer 44

Conversion of OMP to UMP.

Question 45

What activates OMP to UMP conversion?

Answer 45

PRPP (provides the ribose group).

Question 46

What inhibits OMP to UMP conversion?

Answer 46

UMP.

Question 47

What is the function of nucleoside monophosphate kinase?

Answer 47

Transfers a phosphate group between nucleoside monophosphates and ATP.

Question 48

What is the function of nucleoside diphosphate kinase?

Answer 48

Transfers a phosphate group from ATP to nucleoside diphosphates to form triphosphates.

Question 49

What is the role of ATP synthase in nucleotide metabolism?

Answer 49

Generates ATP from ADP and inorganic phosphate.

Question 50

What is the importance of deoxyribonucleotide synthesis?

Answer 50

It is essential for DNA synthesis.

Question 51

What enzyme catalyzes the formation of deoxyribonucleotide diphosphates?

Answer 51

Ribonucleotide reductase.

Question 52

What substrates does ribonucleotide reductase act on?

Answer 52

Ribonucleotide diphosphates.

Question 53

What cofactor is required by ribonucleotide reductase?

Answer 53

NADPH.

Question 54

What proteins mediate electron transfer from NADPH to ribonucleotide reductase?

Answer 54

Thioredoxin or glutaredoxin.

Question 55

How are pyrimidines degraded?

Answer 55

Converted to ammonium ion and then to urea.

Question 56

What reactions occur during pyrimidine degradation?

Answer 56

Dephosphorylation

Question 57

What do degraded pyrimidines produce?

Answer 57

Amino acids that are metabolized to malonyl-CoA.

Question 58

How are purines degraded?

Answer 58

Through dephosphorylation

Question 59

What happens to inosine derivatives in purine degradation?

Answer 59

They are oxidized to uric acid.

Question 60

What is gout?

Answer 60

An inflammation in joints caused by uric acid crystal deposition.

Question 61

What causes difficulty in uric acid excretion in gout?

Answer 61

Accumulation of PRPP due to metabolic deficiencies.

Question 62

What enzyme deficiencies can cause gout?

Answer 62

Hypoxanthine-guanine phosphoribosyl transferase deficiency or glucose-6-phosphatase deficiency.

Question 63

How does glucose-6-phosphatase deficiency promote gout?

Answer 63

It stimulates the pentose phosphate pathway

Question 64

What dietary habits can contribute to gout?

Answer 64

Excessive intake of purine-rich food and alcohol.

Question 65

What drug is used to treat gout?

Answer 65

Allopurinol.

Question 66

How does allopurinol work?

Answer 66

It inhibits xanthine oxidase.