Nucleotides Flashcards

1
Q

What are the components of a nucleotide?

A

ribose/deoxyribse sugar, a nitrogenous base, phosphates

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2
Q

What are the purines?

A

Adenine, guanine

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3
Q

What are the pyrimidines?

A

thymine, cytosine, uracil

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4
Q

What are the components of a nucleoside?

A

base and sugar (NO PHOSPHATE)

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5
Q

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

A

alpha

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6
Q

what suffix ending denotes a purine nucleotide?

A

-osine

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7
Q

what suffix ending denotes a pyrimidine nucleotide?

A

-idine

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8
Q

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

A
  1. energy currency; 2. phosphate source for kinases; 3. coenzymes- FAD, NAD; 4. Substrate activators- UDP, CDP, PAPS; 5. 2nd messengers- cAMP
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9
Q

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

A

ribose-5-phosphate, from the pentose pathway

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10
Q

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

A

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

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11
Q

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

A

glycine, folate derivatives, CO2

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12
Q

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

A

glycine, aspartate, glutamine

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13
Q

What is the first purine formed?

A

IMP inosine monophosphate

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14
Q

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

A
  1. Aspartate binds IMP. 2. fumarate leaves, leaving the nitrogen group. N from aspartate
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15
Q

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

A
  1. IMP is oxidized. 2. glutamine converts C=O to C=NH2. N from glutamine
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16
Q

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

A

cytosolic, in the liver predominantly

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17
Q

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

A

glycine

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18
Q

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

A

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

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19
Q

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

A

step 2- PRPP amidotransferase enzyme

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20
Q

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

A

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

21
Q

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

A

brain, lymphocytes and neutrophils

22
Q

What are the three ring components of pyrimidines?

A

glutamine, aspartate, and CO2

23
Q

What does glutamine donate to pyrimidine strucutre?

A

N

24
Q

What does aspartate donate to pyrimidine structure?

A

N and C

25
Q

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

A

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

26
Q

formation of CTP from UTP requires what amino acid?

A

glutamine

27
Q

What are the two reactions for uracil and thymine recycling?

A

Uracil +ribose-1-phosphate –>uridine and Pi

Uridine + ATP –> UMP + ADP

28
Q

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

A

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.

29
Q

What three enzyme complexes function in the synthesis of pyrimidines?

A
  1. ATCase
  2. transferase-decarboxylase
  3. CTP synthetase (UTP –>CTP)
30
Q

What does the ribonucleotide reductase enzyme do?

A

reduces ribonucleotides to deoxyribonucleotides

31
Q

What are three binding sites on the ribonucleotide reductase enzyme?

A
  1. Catalytic site
  2. Activity site (for allosteric regulators, ATP)
  3. Specifcity site (determines which base to work on)
32
Q

What is a primary product of purine breakdown?

A

uric acid

33
Q

What are the final products of pyrimidine breakdown?

A

b-alanine and b-aminoisobutyrate

34
Q

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

A

xanthin oxidase. requires O2, molybdenum, Fe, Sulfur

35
Q

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

A

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

36
Q

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

A

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

37
Q

What is a use for uric acid?

A

a very good endogenous anti-oxidant

38
Q

What are three types of drugs that inhibit DNA synthesis?

A
  1. structural analogs
  2. antifolates
  3. glutamine antagonists
39
Q

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

A

is a uracil analog that block dTMP synthesis

40
Q

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

A

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

41
Q

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

A

Thymidylate synthase (dUMP–>dTMP)

42
Q

What is gout?

A

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

43
Q

What are some causes of gout?

A

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

44
Q

how does colchicine work? what is it for?

A

for gout, stops lymphocyte movement

45
Q

how does probenicid work? what is it for?

A

for gout, inhibit organic ion transport

46
Q

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

A

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

47
Q

What is used to treat Lesch Nyhan syndrome?

A

allopurinol to bind up PRPP

48
Q

What is von Gierkes syndrome?

A

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

49
Q

What is orotic aciduria?

A

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