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pyrimidine synthesis Flashcards

exam 4 (70 cards)

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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
Orotic Aciduria is caused by the absence of either or both of the enzymes ________ and ______
OPRT or Orotidylate Decarboxylase
26
Characterized by failure of normal growth and severe anemia; high levels of orotic acid are excreted
orotic aciduria
27
Why is orotic acoduria treated with UMP?
to go PAST METABOLIC BLOCK
28
UDP + ATP ←→ UDP + ADP is _________ kinase and UMP + ATP ←→ UDP + ADP is __________ kinase
UDP + ATP ←→ UDP + ADP is Nucleoside Diphosphate kinase and UMP + ATP ←→ UDP + ADP is Base-Specific kinase
29
Cytosine can be formed from the AMINATION of UTP via the action of ____________ UTP + Glutamine + ATP + H2O → CTP + Glutamate + ADP
CTP Synthase
30
Most regulation occurs at CPSII PROMOTED by _____and ___ INHIBITED by __
PROMOTED by PRPP and ATP | INHIBITED by UTP
31
UMP INHIBITS
Orotidylate Decarboxylase
32
REMEMBER, PRPP activates _____________ (committed enzyme of purine synthesis); PRPP is a substrate for this enzyme, HGPRT, and APRT
Amidophosphoribosyl Transferase
33
PRPP activates ____ and is RATE-LIMITING SUBSTRATE of OPRT
CPSII
34
When PRPP accumulates it activates _________ and ___________, meaning De Novo Synthesis of Purines and Pyrimidines tends to occur together
CPSII and Amidophosphoribosyl Transferase
35
Remember, PRPP was used in the Purine Salvage Pathway; the Pyrimidine Salvage Pathway does
NOT use PRPP
36
Free Pyrimidine (base) is combined with _________ with Phosphorylase to form NUCLEOSIDE (pyrimidine)
Ribose-1-Phosphate
37
NUCLEOSIDE (pyrimidine) reacts with ATP and a Kinase to form _________ (pyrimidine)
NUCLEOTIDE
38
Salvage Pathway is also catalyzed by ____with free pyrimidine and PRPP which form the pyrimidine nucleotide
OPRT
39
Thus, Uracil and Thymine catabolism occurs in | _________ and thus DONE by SAME ENZYMES
PARALLEL STEPS
40
Nucleotide (uracil, cytosine, and thymine) conversion to nucleoside occurs via ___________ to give Uridine, Cytidine, and Thymidine
Phosphatase
41
Cytidine is converted to _______ via Cytosine Deaminase
URIDINE
42
Uridine and Thymidine are converted to ______ by Pyrimidine Nucleoside Phosphorylase
FREE BASE
43
Pyrimidine metabolism gives
SOLUBLE PRODUCTS
44
can have their turnover of DNA estimated by measuring the levels of β-aminoisobutyrate
patients undergoing chemotherapy
45
Catabolism of Uracil and Thymine (bases) | Result in __________ and _______
β-alanine and β-aminoisobutyrate
46
ADP, GDP, UDP, CDP are all converted to the -DEOXY form (or reduced) via _________ and uses _____ as a cofactor
Ribonucleotide Reductase and uses NADPH as a cofactor
47
Reaction is used to create –deoxribonucleotides, thus it takes place during
S-Phase
48
it is an inhibitor of tyrosine radicals and thus REDUCES REACTIVITY of enzyme and slows down DNA synthesis in cancerous cells
Hydroxyurea
49
CATALYTIC SITES on Ribonucleotide reductase (and control sites) consist of __________; nearby Tyrosine Radicals can _________ the reactivity of the CATALYTIC SITES
consist of SULFHYDRYL GROUPS and nearby tyrosine radicals INCREASE reactivity
50
Thioredoxin Reductase regenerates the ___________ on Thioredoxin through consumption of NADPH via FADH2 regeneration
Sulfhydryls
51
The Sulfhydryl groups in reibonucleotide reductase step are _________ and the Ribose is _________ to DEOXYRIBOSE
The Sulfhydryl groups are OXIDIZED and the Ribose is REDUCED to DEOXYRIBOSE
52
OVERALL ACTIVITY SITE of reibonucleotide reductase step : ATP (ribose) dATP (deoxy)
ATP (ribose) activates the enzyme | dATP (deoxy) inactivates the enzyme
53
Binding of ATP, dATP, dTTP, and dGTP to the substrate specificity site cause the reduction and thus production of __________
SPECIFIC NUCLEOTIDES
54
dATP will increase or decrese
DECREASE formation of ALL dNTs
55
ATP will promote or inhibit of pyrimidines; or dCTP and dTTP
promote creation
56
Buildup of dTTP causes DECREASE in _______ and instead INCREASE in ________
Buildup of dTTP causes DECREASE in pyrimidine creation and instead INCREASE in dGTP formation
57
dGTP buildup promotes creation of ______ and will cause DECREASE__________by reducing dTTP and dGTP
dGTP buildup promotes creation of dATP and will cause DECREASE ITS OWN FORMATION by reducing dTTP and dGTP
58
Remember, thymine is the version of URACIL used in DNA; thus to create thymine you will use
dUDP
59
dUDP is phosphorylated to
dUTP
60
dUTP is cleaved via dUTP Diphosphohydrolase to
dUMP
61
The “dUMP Reaction” is what results in the creation of dTMP
dTMP
62
Thymidylate Synthase will react ________ and ________ to methylate dUMP to dTMP
N5-N10-Methylene THF and dUMP
63
REMEMBER, the creation of thymine requires N5-N10-Methylene THF to methylate dUMP; thus N5-N10-Methylene THF MUST
BE REGENERATED
64
Dihydrofolate Reductase will reduce _____ to ____ and uses _____
reduces DHF to THF and uses NADPH
65
Serine Hydroxymethyl Transferase is to react THF and ______ and REGENERATE N5-N10-Methylene THF
SERINE
66
REMEMBER, thymine is a unique pyrimidine nucleotide that is present ONLY _______; thus its synthesis can be targeted in chemotherapeutics
in DNA
67
will bind IRREVERSIBLY to Thymidylate Synthase and inactivate the enzyme
FdUMP
68
Methotrexate (Aminopterin,Trimethoprim)
will bind to Dihydrofolate Reductase and cause an inhibition of N5-N10-Methylene THF regeneration meaning dTMP creation STOPS
69
Targets rapidly dividing cells meaning there is effects on the hair follicles and bone marrow
Methotrexate
70
Prolonged usage of methotrexate can lead to amplification of DHF Reductase gene that is _________ to Methotrexate
RESISTANT

Biochem 4 (8 decks)

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