Nucleotide Metabolism

Question 1

What is a nucleoside

Answer 1

Base+sugar

Question 2

What is a nucleotide

Answer 2

Base+sugar+phosphate(s)

Question 3

What are the purines

Answer 3

Adenine and guanine

Question 4

What are the pyrmidines

Answer 4

Thymine, cytosine, uracil

Question 5

What are 5 uses of nucleotides

Answer 5

1. energy currency 2. phosphate source 3. coenzyme 4. substrate activator 5. 2nd messengers

Question 6

What are some complexes that adenosine is part of

Answer 6

SAM, NAD, FAD, cAMP

Question 7

What is the source of ribose 5-phosphate

Answer 7

pentose pathway

Question 8

What converts ribose 5-phosphate to PRPP

Answer 8

PRPP synthetase

Question 9

What is the function of PRPP

Answer 9

purine ring is built with it as a base, and it is added to orotate to make pyrimidines

Question 10

What inhibits PRPP synthetase; what activates it

Answer 10

ADP (end product inhibition); Pi

Question 11

What are the Nitrogen sources for purines

Answer 11

Glycine, aspartate, glutamine

Question 12

What are the carbon sources for purines

Answer 12

glycine, folate derivatives, and CO2

Question 13

What is the first purine formed

Answer 13

IMP inosine monophosphate

Question 14

What is the energy requirement to build a purine ring

Answer 14

6 high energy bonds

Question 15

What is IMP a precursor for

Answer 15

AMP and GMP

Question 16

What is the nitrogen donor to convert IMP to AMP

Answer 16

Aspartate

Question 17

What is the nitrogen donor to convert IMP to GMP

Answer 17

Glutamine

Question 18

Where does purine synthesis take place

Answer 18

In the cytosol, prominent in the liver which exports free bases and nucleosides

Question 19

What is the committed step in purine synthesis

Answer 19

The first one in which amidotransferase swaps NH3 in for 2 Pi

Question 20

How are purine rings recycled

Answer 20

By being re-attached to PPRP

Question 21

Where is purine recycling most prominent

Answer 21

In lymphocytes, PMN, brain tissue. They don’t have the resources to make precursors

Question 22

What is HGPRT

Answer 22

enzyme that recycles guanine and hypoxanthine

Question 23

What is APRT

Answer 23

Enzyme that recycles adenine to AMP

Question 24

What are the nitrogen sources for pyrimidines

Answer 24

Glutamine, aspartate

Question 25

What are the carbon sources for pyrimidines

Answer 25

Aspartate and CO2

Question 26

What is the location for the formation of UMP

Answer 26

Cytosol except for step 3 (oxidation) happens in on the outer surface of the inner mito membrane

Question 27

What are the enzymes involved in uridine formation

Answer 27

CPS II, CPS I, transferase/decarboxylase complex

Question 28

What is the enzyme for converting UTP to CTP

Answer 28

CTP synthase with glutamine for the N source

Question 29

What enzyme forms deoxyribonucleotides

Answer 29

Ribonucleotide reductase

Question 30

What is the product of purine degradation

Answer 30

uric acid

Question 31

What enzyme and cofactors are involved in purine degradation

Answer 31

Xanthine oxidase; O2, molybdenum, iron, sulfur

Question 32

What is the difference between a catalytic site and an activity site

Answer 32

Catalytic is where the conversion happens, activity site affects the speed of the conversion

Question 33

What affects the activity of ribonucleotide reductase

Answer 33

ATP speeds it up, dATP slows it down

Question 34

How does ribonucleotide reductase switch to reducing different nucleotides

Answer 34

product feedback causes it to 'class switch' to a different nucleotide

Question 35

Why does gout happen if someone has an overactive PRPP synthetase

Answer 35

Overproduction and thus over degradation of purines. Uric acid is not very water soluble, so high levels will cause it to precipitate into crystals in tissue

Question 36

What are the breakdown products of cytosine and uracil

Answer 36

Beta-alanine which can be converted into malonate

Question 37

what is malonate used for

Answer 37

Fatty acid synthesis

Question 38

What is the breakdown product of thymine

Answer 38

beta isobutyrate which can be converted into methylmalonate

Question 39

What is methylmalonate used for

Answer 39

It is metabolism for energy as an odd chain fatty acid

Question 40

What are 3 classes of nucleotide inhibitors

Answer 40

1. structural analogs 2. antifolates 3. glutamine antagonists

Question 41

What class of nucleotide inhibitors is 5-fluoroucil

Answer 41

structural analog for uracil; it block the formation of dTMP

Question 42

What class of nucleotide inhibitors is methotrexate

Answer 42

anti folate; it blocks the regeneration of FH4 and synthesis of dTMP via dihydrofolate reductase

Question 43

What enzyme is involved in converting dUMP into dTMP

Answer 43

thymidylate synthase

Question 44

What does allopurinol do

Answer 44

suicide inhibition of xanthine oxidase to stop uric acid formation and react with PRPP to stop de novo synthesis of purines

Question 45

What does probenecid do

Answer 45

inhibits the organic ion transporter in the kidney so that it doesn't reabsorb uric acid

Question 46

what does colchicine do

Answer 46

anti-inflammatory by inhibiting leucocyte movement

Question 47

Why does gout happen if someone has a partially deficient HGPRT

Answer 47

Because purines are not being recycled, they get degraded

Question 48

What is the pKa of uric acid

Answer 48

5.4

Question 49

What causes Lesch-Nyhan Syndrome

Answer 49

X-lined recessive, deficiency of HGPRT activity

Question 50

What happens to the cell in Lesch-Nyhan syndrome

Answer 50

PRPP levels rise, IMP and GMP decrease, de novo purine synthesis increases

Question 51

What are symptoms of Lesch-Nyhan syndrome

Answer 51

Self-mutilation, gout, hyperuricemia, mental retardation, spasticity, urinary tract stones

Question 52

What medications are taken for Lesch-Nyhan syndrome

Answer 52

allopurinol to reduce gout, but there is nothing to reduce the overproduction of purines

Question 53

What causes von Gierke's diease (glycogen storage disease type I)

Answer 53

Glucose-6-phosphatase is deficient

Question 54

What happens to the cell in von Gierke's disease

Answer 54

ribose-5-phosphate and PRPP increase, increased de novo purine synthesis

Question 55

What causes orotic aciduria

Answer 55

Defective conversion of orotate or OMP to UMP

Question 56

What happens to the cell in orotic aciduria

Answer 56

Reduced DNA and RNA synthesis which results in severe anemia

Question 57

What treatments are recommended for orotic aciduria

Answer 57

treatment with uridine can be effective

Question 58

What does glucose-6-phosphotase do

Answer 58

cleave phosphate off glucose-6-phosphate to make Pi and glucose; final step of gluconeogenesis and glycogenolysis