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pyrimidine synthesis Flashcards

exam 4

1
Q

in contrast to the purine rind, the pyrimidine ring is synthesized

A

before being attached to PRPP

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2
Q

synthesized from UTP when the amide nitrogen of glutamine is transferred to the UTP ring by CTP synthetase

A

CTP

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3
Q

free pyrimidine bases are salvaged by

A

OPRT

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4
Q

can be converted to the deoxyribonucleoside diphosphates by reduction of the ribose moiety

A

all four ribonucleosides diphosphates

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5
Q

reaction enzyme that converts NTPs to deoxyribonucleotides diphosphates

A

ribonucleotide reductase

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6
Q

The sulfhydryl groups formed on ribonucleotide reductase as a consequence of this reaction are regenerated by reaction with NADPH, a reaction catalyzed by

A

thioredoxin reductase

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7
Q

Pyrimidines are derived from __________ and ___________

A

CARBAMOYL PHOSPHATE and ASPARTATE

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8
Q

Pyrimidine ring is assembled, then combined with PRPP to form ____

A

UTP

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9
Q

Pyrimidines

A

ALL BEGIN as UTP

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10
Q

is the pyrimidine that binds to Adenine in RNA

A

uracil

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11
Q

is the pyrimidine that binds to Adenine in DNA

A

Thymine

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12
Q

UTP is converted to ______ or the other pyrimidine

A

CTP (cytosine)

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13
Q

CTP can then be turned into _____

A

dCTP

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14
Q

HCO3- + NH4 → Glutamate + Carbamoyl Phosphate

This reaction is catalyzed by ____________ and consumes _____

A

Carbamoyl Phosphate Synthase II (CPS-II) and consumes 2 ATP

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15
Q

CPSII reaction takes place in the

A

cytosol

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16
Q

Carbamoyl Phosphate condenses with _______ to form N-Carbamoylaspartate and it is catalyzed by

A

Aspartate and catalyzed by Catalyzed by Aspartate Transcarbamoylase

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17
Q

Orotate is created via __________ and _________

A

RING-CLOSURE and OXIDATION

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18
Q

N-Carbamoylaspartate is CLOSED via Dihydroorotase to form __________

A

Dihydroorotate

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19
Q

Dihydroorotate is OXIDIZED via Dihydroorotate Dehydrogenase to ______ and results in the formation of _____

A

Orotate and results in the formation of NADH

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20
Q

CPSII, Aspartate Transcarbamoylase, and Dihydroorotase are

A

ALL located on the same enzyme

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21
Q

Orotate reacts with _____ with the action of Orotate Phosphoribosyl Transferase (OPRT) to form________

A

orotate reacts with PRPP to form Orotidylate

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22
Q

IN PURINE SYNTHESIS, the ring is made in

A

ON PRPP

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23
Q

PYRIMIDINE SYNTHESIS, the ring is made

A

separately THEN COMBINED with PRPP

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24
Q

Orotidylate loses CO2 via Orotidylate Decarboxylase to form ___

A

UMP

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25
Q

Orotic Aciduria is caused by the absence of either or both of the enzymes ________ and ______

A

OPRT or Orotidylate Decarboxylase

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26
Q

Characterized by failure of normal growth and severe anemia; high levels of orotic acid are excreted

A

orotic aciduria

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27
Q

Why is orotic acoduria treated with UMP?

A

to go PAST METABOLIC BLOCK

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28
Q

UDP + ATP ←→ UDP + ADP is _________ kinase and UMP + ATP ←→ UDP + ADP is __________ kinase

A

UDP + ATP ←→ UDP + ADP is Nucleoside Diphosphate kinase
and
UMP + ATP ←→ UDP + ADP is Base-Specific kinase

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29
Q

Cytosine can be formed from the AMINATION of UTP via the action of ____________
UTP + Glutamine + ATP + H2O → CTP + Glutamate + ADP

A

CTP Synthase

30
Q

Most regulation occurs at CPSII
PROMOTED by _____and ___
INHIBITED by __

A

PROMOTED by PRPP and ATP

INHIBITED by UTP

31
Q

UMP INHIBITS

A

Orotidylate Decarboxylase

32
Q

REMEMBER, PRPP activates _____________ (committed enzyme of purine synthesis); PRPP is a substrate for this enzyme, HGPRT, and APRT

A

Amidophosphoribosyl Transferase

33
Q

PRPP activates ____ and is RATE-LIMITING SUBSTRATE of OPRT

34
Q

When PRPP accumulates it activates _________ and ___________, meaning De Novo Synthesis of Purines and Pyrimidines tends to occur together

A

CPSII and Amidophosphoribosyl Transferase

35
Q

Remember, PRPP was used in the Purine Salvage Pathway; the Pyrimidine Salvage Pathway does

A

NOT use PRPP

36
Q

Free Pyrimidine (base) is combined with _________ with Phosphorylase to form NUCLEOSIDE (pyrimidine)

A

Ribose-1-Phosphate

37
Q

NUCLEOSIDE (pyrimidine) reacts with ATP and a Kinase to form _________ (pyrimidine)

A

NUCLEOTIDE

38
Q

Salvage Pathway is also catalyzed by ____with free pyrimidine and PRPP which form the pyrimidine nucleotide

39
Q

Thus, Uracil and Thymine catabolism occurs in

_________ and thus DONE by SAME ENZYMES

A

PARALLEL STEPS

40
Q

Nucleotide (uracil, cytosine, and thymine) conversion to nucleoside occurs via ___________ to give Uridine, Cytidine, and Thymidine

A

Phosphatase

41
Q

Cytidine is converted to _______ via Cytosine Deaminase

42
Q

Uridine and Thymidine are converted to ______ by Pyrimidine Nucleoside Phosphorylase

43
Q

Pyrimidine metabolism gives

A

SOLUBLE PRODUCTS

44
Q

can have their turnover of DNA estimated by measuring the levels of β-aminoisobutyrate

A

patients undergoing chemotherapy

45
Q

Catabolism of Uracil and Thymine (bases)

Result in __________ and _______

A

β-alanine and β-aminoisobutyrate

46
Q

ADP, GDP, UDP, CDP are all converted to the -DEOXY form (or reduced) via _________ and uses _____ as a cofactor

A

Ribonucleotide Reductase and uses NADPH as a cofactor

47
Q

Reaction is used to create –deoxribonucleotides, thus it takes place during

48
Q

it is an inhibitor of tyrosine radicals and thus REDUCES REACTIVITY of enzyme and slows down DNA synthesis in cancerous cells

A

Hydroxyurea

49
Q

CATALYTIC SITES on Ribonucleotide reductase (and control sites) consist of __________; nearby Tyrosine Radicals can _________ the reactivity of the CATALYTIC SITES

A

consist of SULFHYDRYL GROUPS and nearby tyrosine radicals INCREASE reactivity

50
Q

Thioredoxin Reductase regenerates the ___________ on Thioredoxin through consumption of NADPH via FADH2 regeneration

A

Sulfhydryls

51
Q

The Sulfhydryl groups in reibonucleotide reductase step are _________ and the Ribose is _________ to DEOXYRIBOSE

A

The Sulfhydryl groups are OXIDIZED and the Ribose is REDUCED to DEOXYRIBOSE

52
Q

OVERALL ACTIVITY SITE
of reibonucleotide reductase step :

ATP (ribose)
dATP (deoxy)

A

ATP (ribose) activates the enzyme

dATP (deoxy) inactivates the enzyme

53
Q

Binding of ATP, dATP, dTTP, and dGTP to the substrate specificity site cause the reduction and thus production of __________

A

SPECIFIC NUCLEOTIDES

54
Q

dATP will increase or decrese

A

DECREASE formation of ALL dNTs

55
Q

ATP will promote or inhibit of pyrimidines; or dCTP and dTTP

A

promote creation

56
Q

Buildup of dTTP causes DECREASE in _______ and instead INCREASE in ________

A

Buildup of dTTP causes DECREASE in pyrimidine creation and instead INCREASE in dGTP formation

57
Q

dGTP buildup promotes creation of ______ and will cause DECREASE__________by reducing dTTP and dGTP

A

dGTP buildup promotes creation of dATP and will cause DECREASE ITS OWN FORMATION by reducing dTTP and dGTP

58
Q

Remember, thymine is the version of URACIL used in DNA; thus to create thymine you will use

59
Q

dUDP is phosphorylated to

60
Q

dUTP is cleaved via dUTP Diphosphohydrolase to

61
Q

The “dUMP Reaction” is what results in the creation of dTMP

62
Q

Thymidylate Synthase will react ________ and ________ to methylate dUMP to dTMP

A

N5-N10-Methylene THF and dUMP

63
Q

REMEMBER, the creation of thymine requires N5-N10-Methylene THF to methylate dUMP; thus N5-N10-Methylene THF MUST

A

BE REGENERATED

64
Q

Dihydrofolate Reductase will reduce _____ to ____ and uses _____

A

reduces DHF to THF and uses NADPH

65
Q

Serine Hydroxymethyl Transferase is to react THF and ______ and REGENERATE N5-N10-Methylene THF

66
Q

REMEMBER, thymine is a unique pyrimidine nucleotide that is present ONLY _______; thus its synthesis can be targeted in chemotherapeutics

67
Q

will bind IRREVERSIBLY to Thymidylate Synthase and inactivate the enzyme

68
Q

Methotrexate (Aminopterin,Trimethoprim)

A

will bind to Dihydrofolate Reductase and cause an inhibition of N5-N10-Methylene THF regeneration meaning dTMP creation STOPS

69
Q

Targets rapidly dividing cells meaning there is effects on the hair follicles and bone marrow

A

Methotrexate

70
Q

Prolonged usage of methotrexate can lead to amplification of DHF Reductase gene that is _________ to Methotrexate

Biochem 4 (8 decks)

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