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DEMS III > puring, pyrimidine, nucleotides > Flashcards

puring, pyrimidine, nucleotides Flashcards

1
Q
  1. Identify the key elements of the structures of purines and pyrimidines and give examples of each.
A
  1. base- single or double ringed structure containing N, C, O and H. 2. Sugar- may or may not be phosphorylated
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2
Q

nucleoside

A

A nucleoside is a base combined with a pentose sugar

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3
Q

nucleotide

A

Nucleoside plus phosphate group

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4
Q

List purines

A

Adenine and guanine- DNA and RNA

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5
Q

list pyrimidines

A

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

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6
Q

methods for making purines/pyrimidines

A

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

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7
Q

compare purine vs pyrimidine de novo synthesis

A

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

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8
Q

Synthesis of activated sugar moiety

A

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

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9
Q

List the sources of atoms for purine synthesis

A

glutamine, glycine, aspartate, tetrahydrofolate and CO2

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10
Q

key regulated step of purine nucleotide synthesis

A

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

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11
Q

first nucleotide produced by purine nucleotide synthesis

A

inosine-5-monophosphate

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12
Q

What is IMP converted to and what dz can result

A

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

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13
Q

regulation of purine synthesis

A

AMP, GMP and IMP inhibit glutamine PRPP amidotransferase

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14
Q

key regulated step of pyrimidine nucleotide synthesis

A

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

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15
Q

how is pyrimidine nucleotide synthesis regulated

A

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

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16
Q

first nucleotide produced by pyrimidine synthesis

A

uracil mono-phosphate (UMP)

17
Q

what is UMP converted to

A

UMP > UTP > CTP (CTP synthase)

18
Q

sources of atoms for pyrimidine synthesis

A

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

19
Q

compare carbamoyl phosphate synthetase I and II

A

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

20
Q

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

A

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

21
Q

How is DNA made

A

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

22
Q

regulation of DNA synthesis

A

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.

23
Q

How is TTP generated

A

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

24
Q

purine breakdown

A

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

25
Q

SCID

A

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

26
Q

gout

A

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

27
Q

pyrimidine breakdown

A

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)

28
Q

what are salvage pathways

A

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

29
Q

adenine phosphoribosyl transferase

A

adenine + PRPP > adenylate (AMP) + Ppi

30
Q

hypoxanthine-guanine phosphoribosyl transferase

A

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

31
Q

Lesch Myhan syndrome

A

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.

32
Q

Methotrexate and 5-florouracil

A

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

33
Q

6-mercaptopurine

A

inhibits AMP synthesis (anti-cancer)

34
Q

azidothymidine (AZT)

A

inhibits viral polymerase (anti HIV)

35
Q

cytosine arabinoside

A

targets DNA polymerase (anti-leukemia)

36
Q

acyclovir

A

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

37
Q

acivicin:

A

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

DEMS III (16 decks)

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