puring, pyrimidine, nucleotides

Question 1

1. Identify the key elements of the structures of purines and pyrimidines and give examples of each.

Answer 1

1. base- single or double ringed structure containing N, C, O and H. 2. Sugar- may or may not be phosphorylated

Question 2

nucleoside

Answer 2

A nucleoside is a base combined with a pentose sugar

Question 3

nucleotide

Answer 3

Nucleoside plus phosphate group

Question 4

List purines

Answer 4

Adenine and guanine- DNA and RNA

Question 5

list pyrimidines

Answer 5

cytosine, thymine and uracil. C and T are DNA, C and U are RNA

Question 6

methods for making purines/pyrimidines

Answer 6

de novo synthesis or recycled - body uses recycling for most of its needs

Question 7

compare purine vs pyrimidine de novo synthesis

Answer 7

purine: purine base made on the ribose, initial nucleotide product is IMP and I is converted to G and A as a monophosphate. Pyrimidine: base ring is synthesized then attached to ribose, initial nucleotide product is UMP, and U is converted to C as a triphosphate

Question 8

Synthesis of activated sugar moiety

Answer 8

ribose-5-phosphate > 5-phosphoribosyl-1-pyrophasphate (via PRPP synthetase)

Question 9

List the sources of atoms for purine synthesis

Answer 9

glutamine, glycine, aspartate, tetrahydrofolate and CO2

Question 10

key regulated step of purine nucleotide synthesis

Answer 10

PRPP + glutamine are used by glutamine phosphoribosyl pyrophosphate amidotransferase (glutamine PRPP amidotransferase) to add the first N to PRPP.

Question 11

first nucleotide produced by purine nucleotide synthesis

Answer 11

inosine-5-monophosphate

Question 12

What is IMP converted to and what dz can result

Answer 12

AMP and GMP- failure of conversion to AMP can lead to form of autism

Question 13

regulation of purine synthesis

Answer 13

AMP, GMP and IMP inhibit glutamine PRPP amidotransferase

Question 14

key regulated step of pyrimidine nucleotide synthesis

Answer 14

carbamoyl phosphate synthetase II catalyzes 2 ATP + CO2 + glutamine > carbamoyl phosphate. Located in cytosol

Question 15

how is pyrimidine nucleotide synthesis regulated

Answer 15

carbamoyl phosphate synthetase II is activated by PRPP and inhibited by UTP

Question 16

first nucleotide produced by pyrimidine synthesis

Answer 16

uracil mono-phosphate (UMP)

Question 17

what is UMP converted to

Answer 17

UMP > UTP > CTP (CTP synthase)

Question 18

sources of atoms for pyrimidine synthesis

Answer 18

CO2, glutamate, aspartate, ribose sugar (added last)

Question 19

compare carbamoyl phosphate synthetase I and II

Answer 19

I: mitochondria, used in urea cycle. II: cytosol, used in pyrimidine synthesis

Question 20

how are di/tri-phosphate forms of nucleotides formed?

Answer 20

kinases take phosphate from ATP donor and transfer it to other nucleotides

Question 21

How is DNA made

Answer 21

ribose is converted to deoxyribose by ribonucleotide reductase. This enzyme works on diphosphates: ADP, GDP, CDP and UDP

Question 22

regulation of DNA synthesis

Answer 22

ribonucleotide reductase is regulated: activated by ATP and inactivated by dATP. This enzyme is also sensitive to the concentrations of individuals dNTPs, so as one builds up, the enzyme changes from one NDP to another.

Question 23

How is TTP generated

Answer 23

UDP > dUDP > dUMP >dTMP (thymidylate synthase) >dTDP > dTTP

Question 24

purine breakdown

Answer 24

occurs by first removing the base from the sugar, yielding a free base (adenosine or guanine). The free bases are then further broken down to uric acid, which is what is excreted from the body in urine

Question 25

SCID

Answer 25

severe combined immunodeficiency disorder- deficiency in adenosine deaminase causes large buildups of dATP in blood which inhibits DNA synthesis leading to T and B cell depletion

Question 26

gout

Answer 26

hyperuricemia due to underexcretion of uric acid (or overproduction).

Question 27

pyrimidine breakdown

Answer 27

Remove base ring from ribose > base ring is opened up and broken down into succinyl CoA, malonyl CoA and acetyl CoA (all aare water soluble)

Question 28

what are salvage pathways

Answer 28

involve enzymes that take free bases and attach them to ribose sugar in the form of PRPP

Question 29

adenine phosphoribosyl transferase

Answer 29

adenine + PRPP > adenylate (AMP) + Ppi

Question 30

hypoxanthine-guanine phosphoribosyl transferase

Answer 30

converts hypoxanthine +PRPP to inosine (IMP) or guanine + PRPP to guanylate (GMP)

Question 31

Lesch Myhan syndrome

Answer 31

Caused by a deficiency in one of the primary enzymes in the purine salvage pathway (HGPRT), leading to higher rates of de novo synthesis of purines. Patients may have gout symptoms, self-mutilating behavior and other severe mental disorders.

Question 32

Methotrexate and 5-florouracil

Answer 32

Targets the thymidylate synthase/folate metabolism cycle (anti cancer)

Question 33

6-mercaptopurine

Answer 33

inhibits AMP synthesis (anti-cancer)

Question 34

azidothymidine (AZT)

Answer 34

inhibits viral polymerase (anti HIV)

Question 35

cytosine arabinoside

Answer 35

targets DNA polymerase (anti-leukemia)

Question 36

acyclovir

Answer 36

targets viral DNA polymerase and RT (anti-herpes simplex)

Question 37

acivicin:

Answer 37

Gln analog, inhibits nucleotide synthesis (most GMP, anti cancer)