Nucleotide Metabolism II

Question 1

There is a key interaction between purine metabolism and the TCA cycle via

Answer 1

Fumarate

Question 2

The interconversion of IMP to adenylosuccinate to AMP and then back to IMP with the release of fumarate

Answer 2

Purine nucleotide cycle

Question 3

Any reaction that serves to replenish the intermediates of another metabolic process is called an

Answer 3

Anapleurotic reaction

Question 4

In muscle cells, allows for increased energy production via the TCA cycle by replenishing supplies of fumarate

Answer 4

Purine nucleotide cycle

Question 5

The parent base is synthesized in its entirety and then added to the PRPP backbone in

Answer 5

De novo pyridine synthesis

Question 6

What is step 1, and also the regulated step, of pyrimidine synthesis?

Answer 6

Synthesis of Carbamoyl phosphate

Question 7

Two molecules of ATP, 1 CO2, and glutamine are converted to carbamoyl phosphate by the enzyme

Answer 7

Carbamoyl synthase II (CPS-II)

Question 8

The enzyme carbamoyl synthase II is activated by

Answer 8

ATP and PRPP

Question 9

Carbamoyl synthetase II is inhibited by the eventual end product of its pathway, which is

-can then be converted to other pyrimidines

Answer 9

UTP

Question 10

Note that carbamoyl phosphate is also synthesized in the

Answer 10

Urea cycle

Question 11

However, in the urea cycle, the key enzyme involved is called

Answer 11

Carbamoyl synthetase I (CPS-I)

Question 12

Located in the mitochondria

Answer 12

CPS-I

Question 13

Located in the cytosol

Answer 13

CPS-II

Question 14

Contributes only two of the atoms that comprise the six-membered pyrimidine ring

Answer 14

Carbamoyl phosphate

Question 15

The remaining 4 atoms of the pyrimidine ring are supplied by

Answer 15

Aspartate

Question 16

Carbamoyl phosphate synthetase and teo other enzymes are catalytic domains of one large polypeptide called

Answer 16

CAD

Question 17

Serves to coordinated the synthesis of pyrimidines in both time and space, minimizing side reactions and ensuring greater efficiency

Answer 17

CAD

Question 18

After one additional reaction that takes place on the outer face of the inner mitochondrial membrane, we end up with a ringed molecule called

Answer 18

Orotate

Question 19

Once the pyrimidine base is formed, we attach it to the

Answer 19

Ribophosphate backbone

Question 20

Orotate is attached to PRPP by the enzyme

Answer 20

Orotate Phosphoribosyl Transferase (OMP)

Question 21

A precursor to the parent pyrimidine UMP

Answer 21

OMP

Question 22

OMP is converted to Uridylate (UMP) by the enzyme

Answer 22

Orotidylate decarboxylase

Question 23

Decreased activity of either orotate phosphoribosyl transferase or orotidylate decarboxylase results in a disease called

Answer 23

Orotic Aciduria

Question 24

Characterized by megaloblastic anemia as well as large amounts of orotate in the urine

Answer 24

Orotic aciduria

Question 25

Results from a deficiency of nucleotides in rapidly diviing marrow cells, leading to fewer, larger immature red cells

Answer 25

Megaloblastic anemia

Question 26

Unlike most causes of megaloblastic anemia, is not corrected by supplementation with folate or vitamin B12

Answer 26

Orotic aciduria

Question 27

We can treat orotic aciduria and bypass the metabolic block with supplementation of

Answer 27

CMP, UMP, or the base Uridine

Question 28

UMP is phosphorylated by a nucleoside monophosphate kinase to produce

Answer 28

UDP

Question 29

UDP is then further phosphorylated by nucleoside diphosphate kinase to form

Answer 29

UTP

Question 30

The only way to synthesize cytosine nucleotides de novo is to

Answer 30

Convert UTP to CTP

Question 31

The conversion of UTP to CTP requires the enzyme

Answer 31

CTP synthetase

Question 32

The conversion of UTP to CTP by CTP synthetase requires

Answer 32

1 ATP and glutamine

Question 33

Serves to negatively inhibit CTP synthetase via a negative feedback mechanism

Answer 33

CTP

Question 34

Can be created from a precursor molecule called deoxyuridine monophosphate (dUMP)

Answer 34

Thymine

Question 35

Thymine can also be formed from the deamination of

Answer 35

Deoxycitidine monophosphate (dCMP)

Question 36

Required for DNA synthesis

Answer 36

Deoxyribonucleotides

Question 37

Deoxyribonucleotides are synthesized from ribonucleotides via the enzyme

Answer 37

Ribonucleotide Reductase

Question 38

Highly expressed in proliferating cells that enter the S-phase of the cell cycle

Answer 38

Ribonucleotide Reductase

Question 39

In order to catalyze the reaction, ribonucleotide reductase requires

Answer 39

NADPH

Question 40

Ribonucleotide reductase is inhibited by

Answer 40

dATP

Question 41

Ribonucleotide reductase is activated by

Answer 41

ATP

Question 42

Ribonucleotide reductase is inhibited by dATP, which prevents the enzyme from reducing

Answer 42

ADP, GDP, and UDP

Question 43

Determination of which substrate preferentially binds the enzymes catalytic site at any given time is regulated by the binding of the NTP to an auxillary site on the enzyme known as the

Answer 43

Substrate specificity site

Question 44

Binding of dATP is only inhibitory if it occupies to the -not inhibitory when bound to the substrate specificity site

Answer 44

Active site

Question 45

Patients with ADA have high levels of

Answer 45

dATP

Question 46

This means that in ADA we see the inhibition of

Answer 46

Ribonucleotide reductase

Question 47

This blocks the production of all deoxyribonucleotides, which prevents the bone marrow from producing

Answer 47

B and T cells

Question 48

Synthesis of thymine nucleotides requires the molecule

Answer 48

dUMP

Question 49

dUMP is formed from the deamintion of

Answer 49

dCMP

Question 50

dUMP is also formed by the action of a phosphatase on

Answer 50

dUTP

Question 51

The main method of synthesizing dUMP

Answer 51

Deamination of dCMP

Question 52

Important in getting rid of excess dUTP to prevent it from getting incorporated into DNA

Answer 52

Phosphorylase activity on dUTP

Question 53

dUMP is ocnverted to thymidylate by the enzyme

Answer 53

Thymidylate synthase

Question 54

This reaction catalyzed by thymidylate synthase requires

Answer 54

N,N-methyleneTHF

Question 55

Covalently inhibits thymidylate synthase

Answer 55

The antitumor agent 5-fluorouracil

Question 56

To block thymidylate synthase, 5-fluorouracil is converted to

Answer 56

5-FdUMP

Question 57

Methotrexate and other inhibitors of DHFR prevents the recycling of THF, which blocks

Answer 57

Purine and TMP synthesis

Question 58

Requires 2 steps. The first step couples the base to a sugar and the second adds a phosphate to the nucleoside

Answer 58

Pyrimidine salvage

Question 59

In step 1, a pyrimidine base and ribose-1-phosphate are converted to a pyrimidine ribonucleoside and inorganic phosphate by

Answer 59

Nucleoside phosphorylase

Question 60

These phosphorylases can act on both

Answer 60

Ribose and deoxyribose substrates

Question 61

A pyrimidine nucleoside is phosphorylated to a pyrimidine nucleoside monophosphate by a

Answer 61

Nucleoside kinase

Question 62

Salvges the nucleoside thymidine to TMP

Answer 62

Thymidine kinase

Question 63

Interestingly, the herpes simplex virus encodes its own

Answer 63

Thymidine kinase

Question 64

This virus uses its own thymidine kinase to augment nucleotide supplies to promote its own replication

Answer 64

Herpes simplex virus

Question 65

A guanosine analog that interferes with viral replication

Answer 65

Acyclovir

Question 66

Gets phorphorylated by the viral thymidine kinase and gets preferentially incorporated into viral DNA, resulting in premature DNA chain termination

Answer 66

Acyclovir

Question 67

The catabolism of pyrimidines leads to

Answer 67

Highly soluble products

Question 68

CMP and UMP are degraded to

Answer 68

β-alanine

Question 69

TMP is degraded to

Answer 69

β-­‐aminoisobutyrate

Question 70

The degredation of pyrimidines results in the release of

Answer 70

Ammonia and CO2

Question 71

The single most important risk factor for developing gout

Answer 71

Serum Urate (SU)

Question 72

A sustained elevation of SU is essential to developing gout, but is it sufficient to cause the disease?

Answer 72

No

Question 73

Do the majority of patients with hyperuricemia develop gout?

Answer 73

No

Question 74

Uric acid crystalizes at a level of

Answer 74

6.8 mg/dL

Question 75

Abrupt and rapid onset causing severe pain. Often at night/early A.M.

Answer 75

Acute gout

Question 76

An inflammatory granuloma

Answer 76

The Tophus

Question 77

Deposits of monosodium urate crystals (MSU) crystals are surrounded by

Answer 77

Foreign body ganulomas

Question 78

All gout is

Answer 78

Tophaceous