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Biochemistry 2 > Biosynthesis of Nucleotides > Flashcards

Biosynthesis of Nucleotides Flashcards

1
Q

What did John Buchanan contribute?

A

Understanding of how purines are synthesized

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2
Q

What are nucleotides?

What do they carry?

A

Building blocks/precursors of nucleic acids.

Energy (ATP / GTP)

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3
Q

How do nucleotides initiate glycogenesis?

A

Before glucose can be polymerized, UDP-glucose (a nucleotide) must be formed

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4
Q

How can a nucleoside be made a nucleotide?

A

Add phosphate group on C5

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5
Q

What are the 3 pentose sugars?

A

Ribose and deoxyribose

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6
Q

On what end is a free sugar available for bonding on a nucleoside?

A

3’ end

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7
Q

Purine vs Pyrimidine

A

Purine: 2 carbon-nitrogen rings – Adenine and guanine

Pyrimidine: 1 carbon-nitrogen ring – cytosine, thymine, uracil

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8
Q

What bond connects nucleotides? Between what Carbons?

A

phosphodiester bond between C3 of one pentose sugar and C5 of another

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9
Q

What is the difference between a nucleotide, nucleoside, and nitrogenous base?

A

Nitrogenous base: purine + pyrimidine
Nucleoside: pentose sugar + nitrogenous ring
Nucleotide: Phosphate group: pentose sugar + nitrogenous base

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10
Q

What are the 2 pathways of nucleotide synthesis?

A

De-novo: synthesis of metabolic precursors (AA, ribose-5-phosphate, CO2, NH3/ammonia)

Salvage pathway: purine/pyrimidine bases released from the degradation of nucleotides are recycled to make new mRNA/nucleotides (doesn’t need precursors)

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11
Q

Can purine/pyrimidine bases be synthesized as independent molecules?

A

No, they are ALWAYS part of a nucleotide.

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12
Q

What are purine rings always built upon?

A

a Ribose phosphate

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13
Q

What are pyrimidine rings first synthesized as? What are they attached to after?

A

Orotate, then attached to ribose phosphate

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14
Q

What is the precursor for 5-phosphoribosyl 1-pyrophosphate (PRPP)?

A

Ribose-5-phosphate

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15
Q

What AA is the precursor of purines?

A

Glycine

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16
Q

What AA is the precursor of pyrimidines?

A

Aspartate

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17
Q

What is the role of glutamine in nucleotide synthesis?

A

Amino group donor

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18
Q

What is the 1st step in de novo synthesis of purines?

A

PRPP joins with glutamine which gives PRPP an amino group

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19
Q

What does glycine provide in the de novo synthesis of purines?

A

Backbone

20
Q

What step in the de novo synthesis of purines only occur in higher eukaryotes?

A

AIR to CAIR

21
Q

What is the purine ring built on in de novo synthesis of purines?

A

PRPP

22
Q

What is the end product of the de novo synthesis of purines? Which is then converted to what?

A

IMP –> AMP/GMP

23
Q

In order to convert IMP to AMP, what AAs are used and how do they alter the molecule? de novo synthesis of purines

A

Aspartate gives an amino group (GTP dependent)

Fumarate backbone is then removed & amino group added to 6th carbon, forming AMP

24
Q

In order to convert IMP to GMP, what AAs are used and how do they alter the molecule? de novo synthesis of purines

A

IMP –> XMP

From XMP –> GMP:

  • ATP dependent.
  • amino group added from Glutamine onto 2nd C
  • Glutamate backbone leaves
25
Q

Where does specific regulation start occurring in the de novo synthesis of purines?

A

IMP –> AMP/GMP

26
Q

What limits the synthesis of AMP? GMP? de novo synthesis of purines

A

GTP limits AMP

ATP limits GTP

Reciprocal inhibition.

27
Q

What inhibits the reaction from Ribose-5-phosphate –> PRPP in de novo synthesis of purines?

A

ADP

28
Q

What inhibits the reaction from PRPP –> 5-phosphoribosylamine in de novo synthesis of purines?

A

AMP, GMP, IMP

29
Q

What does the production of AMP from IMP inhibit in de novo synthesis of purines?

A

AMP inhibits 1st step of IMP–>AMP production

30
Q

What does the production of GMP from IMP inhibit in de novo synthesis of purines?

A

GMP inhibits 1st step of IMP–>GMP production

31
Q

What are the precursors of de novo synthesis of pyrimidines?

A

Aspartate, carbomoyl phosphate, PRPP

32
Q

Carbomoyl phosphate is required for de novo synthesis of pyrimidines in what part of the cell? Via what enzyme?

A

Cytosol via Carbamoyl phosphate synthetase 2

33
Q

What AA is used to produce orotate in de novo synthesis of pyrimidines? What is required for orotate to be converted to its end product?

A

Aspartate

Orotate needs to be built on PRPP, if not it can’t be converted to its end product

34
Q

What is the 1st nucleotide synthesized in de novo synthesis of pyrimidines? What is it ultimately converted to? Which AA helps? How?

A

UMP. CTP - Glutamine donates amino group on 4th Carbon

35
Q

What inhibits the de novo synthesis of pyrimidines?

A

CTP (product) inhibits 1st enzyme of the de novo synthesis of pyrimidines

36
Q

What is the main enzyme that participates in the conversion of riboneucleotides to deoxyriboneucleotides?

A

Ribonucleotide reductase

37
Q

What two enzymes transmit electrons from NADPH in the reduction of ribonucleotides to deoxyribonucleotides via ribonucleotide reductase?

A

Glutaredoxin and thioredoxin

38
Q

Discuss the electron path that involves glutaredoxin?

A

NADPH –> (GSSG–>2GSH) –> Glutaredoxin –> ribonucleotide reductase which converts (NDP–>dNDP + H2O)

39
Q

What does ribonucleotide reductase transfer to NDP to create dNDP + H2O

A

2 (-SH) groups

40
Q

What is the cofactor of Gultaredoxin?

A

2GSH

41
Q

What is the cofactor of Thioredoxin?

A

FADH2

42
Q

What is dTMP derived from?

A

CDP or UDP

43
Q

What differentiates Thiamine and Uracil?

A

Thiamine has a methyl group on C5

44
Q

Draw out the mechanism of CDP/UDP to dTMP.

A

Check

45
Q

What intermediate of the pentose phosphate pathway is PRPP made from?

A

Ribose-5-phosphate

46
Q

When high [NADPH] inhibits the pentose phosphate pathway, what doe G6P do?

A

It does glycolysis

Biochemistry 2 (8 decks)

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