Unger

Front 1

Describe the linkage in a purine nucleoside

Back 1

beta glycosidic linkage from N9 of purine to C1' of pentose

Front 2

Describe the linkage in a pyrimidine nucleoside

Back 2

beta glycosidic linkage from N1 of pyrimidine to C1' of pentose

Front 3

Describe the linkages in a purine nucleotide

Back 3

beta glycosidic linkage from N9 of purine to C1' of pentose and a phosphate esterified to C5' of pentose

Front 4

Desribe the linkages of a pyrimidine nucleotide

Back 4

beta glycosidic linkage from N1 of pyrimidine to C1' of pentose and a phosphate esterified to C5' of pentose

Front 5

Atoms of the purine ring donated by

Back 5

amino acids (glycine, aspartic acid, glutamine), THFA (formyltetrahydrofolate), and CO2

Front 6

The conversion of IMP to AMP requires what energy source?

Back 6

GTP

Front 7

The conversion of IMP to GMP requires what energy source?

Back 7

ATP

Front 8

Role of glutamine in purine ring synthesis

Back 8

Glutamine donates two nitrogens, one of which becomes N9

Front 9

Role of glycine in purine ring synthesis

Back 9

Glycine donates its entire structure (2 C's and a N) to the purine ring

Front 10

Colchicine

Back 10

prevents formation of microtubules, decreasing movement of neutrophils into affected area. No affect on uric acid levels

Front 11

Febuxostat

Back 11

non-purine xanthine oxidase inhibitor

Front 12

Allopurinol

Back 12

hypoxanthine analogue which inhibits xanthine oxidase. Results in accumulation of xanthine and hypoxanthine which are more soluble than uric acid

Front 13

Adenosine deaminase deficiency

Back 13

A deficiency in ADA leads to an accumulation of adenosine which is converted to its d/r nucleotide. dATP levels rise, which inhibits ribonucleotide reductase, thus preventing DNA synthesis. Tx: BMT, ERT

Front 14

Severe Combined Immunodeficiency Disease (SCID)

Back 14

A severe form of ADA deficiency involving T-cell, B-cell, and NK cell deficiencies

Front 15

Purine Nucleoside Phosphorylase Deficiency (PNP)

Back 15

associated with T-cell deficiency only (as compared to SCID)

Front 16

Lesch-Nyhan

Back 16

hyperuricemia due to HGPRT deficiency (can't salvage hypoxanthine or guanine), leads to increase in PRPP and decrease in IMP and GMP all which leads to increased purine synth, degradation and uric acid. Symptoms include gout and neurologic (ataxia, self mutilation, etc)

Front 17

Ribose-5-phosphate

Back 17

plays a role in de nove purine synth, yields PRPP when combined with ATP and PRPP synthetase

Front 18

PRPP

Back 18

acts as a scaffold for purine ring synth, when combined with glutamine and amidophosphoribosyl transferase, yields PRNH2. This step commits the pathway to purine synth

Front 19

PRNH2

Back 19

5-phosphoribosyl 1-amine

Front 20

Regulation of PRPP to PRNH2 step

Back 20

PRPP stimulates this transition where as AMP, GMP, IMP, and ALMP inhibit. These are end-products

Front 21

PRPP synthetase

Back 21

along with ATP, converts ribose-5-phosphate to PRPP

Front 22

amidophosphoribosyl transferase

Back 22

along with glutamine, converts PRPP to PRNH2

Front 23

Deoxyribonucleotides are formed by the reduction of _________

Back 23

ribonucleoside DIphosphates

Front 24

What is the source of the amine group that is added to IMP resulting in AMP?

Back 24

aspartate

Front 25

What is the source of the amine group that is added to IMP resulting in GMP?

Back 25

glutamine

Front 26

How many steps does it take to convert IMP to AMP or GMP?

Back 26

2 steps

Front 27

Explain the process of turning IMP into AMP

Back 27

aspartate is added to IMP with the help of GTP, then in the second step, aspartate leaves in the form of fumarate leaving an amine group which yields AMP

Front 28

Explain the process of turning IMP into GMP

Back 28

IMP is oxidized first and then glutamine donates an amine to the oxidized site with help from ATP

Front 29

Name the three sites at which feedback inhibition regulates de novo purine nucleotide synthesis

Back 29

Feedback regulation occurs on the amidotransferase from end products GMP and AMP, AMP inhibits the conversion of IMP to adenylosuccinate (1st step spec to AMP), and GMP inhibits the conversion of IMP to xanthylate (1st step spec to GMP)

Front 30

Does the feedback regulation of AMP affect the synthesis of GMP?

Back 30

No

Front 31

Does the feedback regulation of GMP affect the synthesis of AMP?

Back 31

No

Front 32

During purine biosynthesis, are AMP, GMP, and IMP concentrations 1:1:1?

Back 32

No, they are synergistic meaning the whole is greater than the sum of its parts

Front 33

Is there any cross-regulation that occurs between AMP and GMP?

Back 33

Yes, GMP synthesis is dependent on ATP and AMP synthesis is dependent on GTP

Front 34

Why can small amounts of PRPP greatly affect the rxn rate of PRPP -> PRNH2?

Back 34

Because there is so much more amidophosphoribosyl transferase than PRPP, the enzyme is never saturated. Also, PRPP is an activator of amidotransferase further accelerating the rxn

Front 35

Which immunosuppressive drug inhibits the first step in forming AMP and GMP from IMP?

Back 35

6-mercaptopurine

Front 36

The presence of GMP inhibits what steps in purine synthesis?

Back 36

PRPP and the step from IMP to xanthylate

Front 37

The presence of AMP inhibits which steps in purine synthesis?

Back 37

PRPP and the step from IM Pto adenylosuccinate

Front 38

Thioredoxin reductase

Back 38

reduces thioredoxin with H from NADPH

Front 39

Thioredoxin

Back 39

provides H to ribonucleotide reductase so that it can reduce NDP to dNDP

Front 40

Ribonucleotide reductase

Back 40

reduces NDP to dNDP

Front 41

3 proteins that are important in transforming NDP to dNDP

Back 41

ribonucleotide reductase, thioredoxin, and thioredoxin reductase

Front 42

Examples of ribonucleotide reductase inhibitors

Back 42

hydroxyurea (a drug) and dATP (as seen in ADA deficiency)

Front 43

what kind of ribonucleotides are reduced to deoxyribonucleotides?

Back 43

only diphosphates!

Front 44

Ribonucleotide reductase is reduced by _______

Back 44

Thioredoxin

Front 45

Thioredoxin gets reduced by

Back 45

NADPH

Front 46

Name the five catabolic enzymes

Back 46

pancreatic nucleases, purine 5' nucleotidase, purine nucleoside phosphorylase, adenosine deaminase, and xanthine oxidase

Front 47

Name two salvage enzymes

Back 47

adenine phosphoribosyl transferase (APRT) and hypoxanthine-guanine phosphoribosyl transferase (HGPRT)

Front 48

What disease is associated with HGPRT deficiency?

Back 48

lesch-nyhan

Front 49

A frameshift mutation prevents humans from having what important enyzme in purine metabolism?

Back 49

urate oxidase (uricase)

Front 50

Rasburicase

Back 50

a PEGylated protein which replaces urate oxidase

Front 51

Pancreatic nucleases

Back 51

transform nucleic acids to nucleotides

Front 52

Purine 5' nucleotidase

Back 52

converts nucleotides to nucleosies by removing a phosphate

Front 53

Purine nucleoside phosphorylase

Back 53

converts nucleosides to free purine bases

Front 54

xanthine oxidase

Back 54

works to convert hypoxanthine to xanthine, and xanthine to uric acid. Inhibited by allopurinol

Front 55

Xypoxanthine and guanine are both converted to _____ by ______

Back 55

xanthine; xanthine oxidase

Front 56

APRT

Back 56

converts adenine back to AMP

Front 57

HGPRT

Back 57

converts hypoxanthine to IMP and guanine to GMP

Front 58

What do APRT and HGPRT use as a source of ribose-5-phosphate?

Back 58

PRPP

Front 59

PRPP + allopurinol yields

Back 59

allopurinolribonucleoside mono-PO4 or ALMP

Front 60

Name 3 ways allopurinol works to reduce uric acid production

Back 60

inhibits xanthine oxidase, uses up the substrate (PRPP) in salvage rxns, ALMP end product feedback inhibits rate limiting step

Front 61

Adenine

Back 61

6-aminopurine

Front 62

Guanine

Back 62

2-amino,6-oxypurine

Front 63

Cytosine

Back 63

2-oxy,4-aminopyrimidine

Front 64

Uracil

Back 64

2,4-dioxypyrimidine

Front 65

Thymine

Back 65

2,4-dioxy,5-methylpyrimidine