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2) Biochemistry II > Synthesis of Nucleotides > Flashcards

Synthesis of Nucleotides Flashcards

1
Q

What are the roles of nucleotides?

A

o Precursors of nucleic acids
o Carriers of energy (ATP and GTP)
o Components of cofactors (NAD, FAD, CoA)
o Initiators of glycogenesis: before glucose can be put in a glycogen chain, it must be
modified by UDP-Glucose (nucleotide)
o Secondary messengers (cyclic AMP)

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2
Q

Who contributed to the synthesis of purines?

A

John Buchanan

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3
Q

What is a nucleoside?

A

nitrogenous base + pentose sugar

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4
Q

What is a nucleotide?

A

nitrogenous base + pentose sugar + phosphate group

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5
Q

What is a nucleic acid?

A

a series of nucleotides attached in a chain (DNA and RNA)

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6
Q

How are nucleotides linked together?

A

Two pentose sugars of nucleotides form a phosphodiester bond between the 5’ and 3’ carbon

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7
Q

Differentiate the 5’ and 3’ end of a nucleotide. Which one is available for bonding?

A

o One end of a nucleotide contains a free phosphate group on the 5’ (5’ end)
o One end of the nucleotide on the 3’ is available for bonding (3’ end)

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8
Q

The phosphate group is added to which carbon of the pentose sugar?

A

5’ carbon

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9
Q

What are purines? What are the two?

A
  • Two carbon-nitrogen rings

- Guanine and Adenine

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10
Q

What are pyrimidines? What are the three?

A
  • One carbon-nitrogen ring

- Cytosine, Thymine, Uracil

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11
Q

What are the two types of nucleotide synthesis pathways?

A
  • De novo pathway

- Salvage pathway

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12
Q

What is the de novo pathway?

A

Synthesis of nucleotides from metabolic precursors, such as amino acids, ribose 5-phosphate, CO2, and NH3

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13
Q

What is the salvage pathway?

A
  • Purine and pyrimidine bases are released from the degradation of nucleotides
  • Metabolic precursors are not needed for this type of synthesis
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14
Q

Are nucleotides synthesized as dependent or independent molecules?

A

Dependent (always found as part of an entity), unlike glucose and fatty acids

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15
Q

What are purine rings built upon?

A

Ribose phosphate

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16
Q

What are pyrimidine rings built upon?

A
  • First synthesized as “orotate”

- Then, attached to ribose pohsphate

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17
Q

Which precursor of nucleotide synthesis is synthesized from the pentose phosphate pathway?

A

5-phosphoribosyl-1-pyrophosphate (PRPP), which is synthesized from ribose-5-phosphate

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18
Q

Which amino acid precursors provide the carbon backbone in purines? What about pyrimidines?

A
  • Purine: glycine

- Pyrimidine: aspartate

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19
Q

What is the amino group donor in nucleotide synthesis?

A

Glutamine

20
Q

How are the levels of the nucleotide pools?

A

Kept low

21
Q

What is the first step in the de novo synthesis of purines? Which enzyme catalyzes this step?

A
  • Enzyme: Glutamine-PRPP amidotransferase

- PRPP is combined with Glutamine

22
Q

In the de novo synthesis of purines, how does the conversion of AIR to CAIR differ between Eukaryotes and Prokaryotes? What causes the difference?

A
  • Eukaryotes: single-step
  • Prokaryotes: two-step
  • Eukaryotes possess the enzyme AIR carboxylase
23
Q

What is the end-product of the de novo synthesis of purines? What must it be converted to?

A
  • Inosinate (IMP), which is a monophosphate

- Must be converted to either an Adenylate (AMP) or a Guanylate (GMP)

24
Q

What provides the amino group when IMP is synthesized into AMP? Where is the amino group added? What provides the energy?

A
  • Amino: Aspartate
  • 6th carbon of IMP
  • Energy: GTP
25
Q

Which enzymes are used in the conversion of IMP to AMP?

A
  • Adenylosuccinate synthetase

- Adenylosuccinate lyase, which removes the fumarate carbon backbone

26
Q

What provides the amino group when IMP is synthesized into GMP? Where is the amino group added? What provides the energy?

A
  • Amino: Glutamine
  • 2nd carbon of IMP
  • Energy: ATP
27
Q

Which enzymes are used in the conversion of IMP to GMP?

A
  • IMP dehydrogenase

- XMP-glutamine amidotransferase

28
Q

How is the de novo synthesis of purines regulated? What causes overall inhibition?

A
  • Negative regulation: end-products inhibit

- Overall inhibition: IMP inhibition

29
Q

What is the reciprocal inhibition in the regulation of the de novo synthesis of purines?

A
  • GTP limits the synthesis of AMP

- ATP limits the synthesis of GMP

30
Q

What are the three precursors to the de novo synthesis of pyrimidines?

A
  • Aspartate
  • Carbamoyl phosphate
  • PRPP
31
Q

Where is carbamoyl phosphate also located?

A

In the urea cycle

32
Q

What is the first step to the de novo synthesis of pyrimidines? What is the enzyme? What does it produce?

A
  • Aspartate reacts with carbamoyl phosphate
  • Enzyme: aspartate trans-carbamoylase
  • Produces orotate
33
Q

What synthesizes the carbamoyl phosphate used for the de novo synthesis of pyrimidines?

A

Cytoplasmic carbamoyl phosphate synthetase II (similar to urea cycle)

34
Q

What does orotate require to be converted to a nucleotide?

A

It NEEDS to be build upon PRPP

35
Q

What is produced once orotate is build upon PRPP?

A
  • UMP –> UTP (uses 2 ATPs)
36
Q

UTP receives the amino group from what? At which carbon?

A
  • 4th carbon

- Glutamine

37
Q

Once UTP has received its amino group, what is it converted to? What does it require?

A
  • Requires energy from ATP

- Creates CTP

38
Q

What is required for the reduction of ribose nucleotides to deoxyribonucleotides? Who donates it?

A
  • Hydrogen atoms

- Donated by NADPH

39
Q

What are the two ways to donate hydrogen atoms from NADPH to ribonucleotides?

A
  • Glutaredoxin

- Thioredoxin

40
Q

What does glutaredoxin require?

A

Glutathione

41
Q

What does thioredoxin require?

A

FAD

42
Q

What is the difference between a ribonucleotide and a deoxyribonucleotide?

A

OH- is replaced by H at the 2nd carbon of the ribose sugar

43
Q

What is dTMP derived from?

A

dCDP and dUMP

44
Q

Which phase of the pentose phosphate pathway generates PRPP? What else does the phase generate?

A
  • Oxidative phase

- NADPH and ribose-5-phosphate

45
Q

What does the non-oxidative phase of the pentose phosphate pathway generate?

A

Regenerates G-6-P from R-5-P

46
Q

What is the non-oxidative phase of the pentose phosphate pathway used for?

A

o Used in tissues requiring more NADPH than R-5-P, such as the liver and adipose tissue
o More metabolism means more oxidative stress, for which you need NADPH

47
Q

What regulates the partitioning of glucose into glycolysis over the pentose phosphate pathway?

A

NADPH: high NADPH inhibits the pentose phosphate pathway

2) Biochemistry II (23 decks)

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