Nucleotides

Question 1

What are the components of a nucleotide?

Answer 1

ribose/deoxyribse sugar, a nitrogenous base, phosphates

Question 2

What are the purines?

Answer 2

Adenine, guanine

Question 3

What are the pyrimidines?

Answer 3

thymine, cytosine, uracil

Question 4

What are the components of a nucleoside?

Answer 4

base and sugar (NO PHOSPHATE)

Question 5

which phosphate group is closest to the sugar? the alpha, beta or delta phosphates?

Answer 5

alpha

Question 6

what suffix ending denotes a purine nucleotide?

Answer 6

-osine

Question 7

what suffix ending denotes a pyrimidine nucleotide?

Answer 7

-idine

Question 8

What are 5 uses of nucleotides other than DNA and RNA?

Answer 8

1. energy currency; 2. phosphate source for kinases; 3. coenzymes- FAD, NAD; 4. Substrate activators- UDP, CDP, PAPS; 5. 2nd messengers- cAMP

Question 9

What molecule ‘starts’ the biosynthesis of purines? Where does it come from?

Answer 9

ribose-5-phosphate, from the pentose pathway

Question 10

What is the first step in the biosynthesis of purines? name enzyme, activators and inhibitors.

Answer 10

PRPP if formed from ribose-5-phosphate. Enzyme: PRPP synthetase. Activated by inorganic phosphate (a reactant). Inhibited by ADP (an eventual product)

Question 11

In the biosynthesis of purines, where do the carbons come from?

Answer 11

glycine, folate derivatives, CO2

Question 12

In the biosynthesis of purines, where do the nitrogens come from?

Answer 12

glycine, aspartate, glutamine

Question 13

What is the first purine formed?

Answer 13

IMP inosine monophosphate

Question 14

How is AMP made from IMP? Where does the N come from?

Answer 14

1. Aspartate binds IMP. 2. fumarate leaves, leaving the nitrogen group. N from aspartate

Question 15

How is GMP made from IMP? Where does the N come from?

Answer 15

1. IMP is oxidized. 2. glutamine converts C=O to C=NH2. N from glutamine

Question 16

Where (cellular location and tissue location) does biosynthesis of purines occur?

Answer 16

cytosolic, in the liver predominantly

Question 17

What amino acid donates a majority of it’s structure to the purines?

Answer 17

glycine

Question 18

What are two enzymes involved in the biosynthesis of purines? What inhibits them?

Answer 18

PRPP synthetase and PRPP amidotransferase. Inhibited by GMP, AMP (feedback inhibition)

Question 19

What step in the biosynthesis of purines is the committed step?

Answer 19

step 2- PRPP amidotransferase enzyme

Question 20

What two enzymes recycle purine rings? which is most active?

Answer 20

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

Question 21

Where are HGPRT and APRT most active? (which tissues)

Answer 21

brain, lymphocytes and neutrophils

Question 22

What are the three ring components of pyrimidines?

Answer 22

glutamine, aspartate, and CO2

Question 23

What does glutamine donate to pyrimidine strucutre?

Answer 23

N

Question 24

What does aspartate donate to pyrimidine structure?

Answer 24

N and C

Question 25

How is UDP formed? name enzyme, cellular location and the two-step process

Answer 25

ring is formed, then PRPP sugar is added. carbamoyl phosphate synthetase II. In the cytosol, with one step in the inner mitochondrial matrix

Question 26

formation of CTP from UTP requires what amino acid?

Answer 26

glutamine

Question 27

What are the two reactions for uracil and thymine recycling?

Answer 27

Uracil +ribose-1-phosphate -->uridine and Pi | Uridine + ATP --> UMP + ADP

Question 28

What are three differences between the urea cycle and the formation of pyrimidines?

Answer 28

urea cycle is in the mitochondrial matrix, pyrimidine formation is in the cytosol. PF uses CPS II, UC uses CPS I. Glutamine in N source in PF. Ammonium is N source in UC.

Question 29

What three enzyme complexes function in the synthesis of pyrimidines?

Answer 29

1. ATCase 2. transferase-decarboxylase 3. CTP synthetase (UTP -->CTP)

Question 30

What does the ribonucleotide reductase enzyme do?

Answer 30

reduces ribonucleotides to deoxyribonucleotides

Question 31

What are three binding sites on the ribonucleotide reductase enzyme?

Answer 31

1. Catalytic site 2. Activity site (for allosteric regulators, ATP) 3. Specifcity site (determines which base to work on)

Question 32

What is a primary product of purine breakdown?

Answer 32

uric acid

Question 33

What are the final products of pyrimidine breakdown?

Answer 33

b-alanine and b-aminoisobutyrate

Question 34

What is a key enzyme in purine degradation? what cofactors does it require?

Answer 34

xanthin oxidase. requires O2, molybdenum, Fe, Sulfur

Question 35

What can serve as an energy source? purines or pyrimidines?

Answer 35

pyrimidines- degrade to malonate and methylmalonic, which crosses with odd-chain FA metabolism and FA generation

Question 36

What is the process of GMP degradation compared to the process of AMP degradation?

Answer 36

AMP: remove N, then remove Pi, then remove sugar GMP: remove Pi, then remove sugar, then remove N --> xanthine --> uric acid --> urea

Question 37

What is a use for uric acid?

Answer 37

a very good endogenous anti-oxidant

Question 38

What are three types of drugs that inhibit DNA synthesis?

Answer 38

1. structural analogs 2. antifolates 3. glutamine antagonists

Question 39

how does 5-fluorouracil function as an anti-cancer therapy?

Answer 39

is a uracil analog that block dTMP synthesis

Question 40

how dose methotrexate function as an anti-cancer therapy? or anti-psoriasis therapy?

Answer 40

a folic acid analog, inhibits THF, thereby inhibiting dUMP-->dTMP synthesis

Question 41

What enzyme is a common target for anti-cancer drugs (to stop cell replication)?

Answer 41

Thymidylate synthase (dUMP-->dTMP)

Question 42

What is gout?

Answer 42

deposition of urate crystals in the joints (NOT uric acid in the kidneys)

Question 43

What are some causes of gout?

Answer 43

abnormal or deficient PRPP/ HGPRT. PRPP build-up reacts with allopurinol, which usually scavenges uric acid. lymphocytes take up uric acid, then rupture in the joints

Question 44

how does colchicine work? what is it for?

Answer 44

for gout, stops lymphocyte movement

Question 45

how does probenicid work? what is it for?

Answer 45

for gout, inhibit organic ion transport

Question 46

What is Lesch-Nyhan syndrome? what are some symptoms?

Answer 46

a neurological disease, X-linked recessive, deficiency of HGPRT. intracellular PRPP increases. Symptoms: gout, hyperuricemia, urinary tract stones, mental retardation, self-mutilation

Question 47

What is used to treat Lesch Nyhan syndrome?

Answer 47

allopurinol to bind up PRPP

Question 48

What is von Gierkes syndrome?

Answer 48

Glycogen Storage Disease type 1: deficient glucose 6-phosphate. Causes ribose-5-phosphate and PRPP increases and increased purine synthesis

Question 49

What is orotic aciduria?

Answer 49

cant convert orotate/orotidine monophosphate to UMP. --> decreased DNA and RNA synthesis, severe anemia. uridine treatment can be effective