Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

Tissues > T08 - Purine and Pyrimidine Metabolism > Flashcards

T08 - Purine and Pyrimidine Metabolism Flashcards

1
Q

What is the basic structure of purines?

A

9-membered heterocyclic, aromatic double ring w/ 5 carbons and 4 nitrogens

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Draw the generic structure of a purine. Identify where substituents can be placed.

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the oxopurines?

A

hypoxanthine (1 OH group)

xanthine (2 OH groups)

uric acid (3 OH groups)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the significance of hypoxanthine?

A

initial product of de novo purine synthesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the significance of uric acid?

A

end product of purine degradation that is excreted in urine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Knowing the structure of the oxopurines, how are the aminopurines adenine and guanine produced?

A

replace the -OH group in hypoxanthine with -NH2 → adenine

replace one of the -OH groups in xanthine with -NH2 → guanine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is the generic structure of pyrimidines?

A

single 6-membered heterocyclic ring w/ 2 nitrogens and 4 carbons

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the initial product of pyrimidine biosynthesis?

A

orotic acid, the precursor of the other pyrimidines

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is the significance of orotic acid?

A

initial product of pyrimidine biosynthesis, therefore the precursor to other pyrimidines

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

(T/F) Orotic acid’s only metabolic purpose is to serve as a pyrimidine precursor.

A

True. It does not have any other metabolic functions.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Decarboxylation of orotic acid produces

A

uracil

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Substituting a keto group of uracil with an amino group yields

A

cytosine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is the relationship between cytosine, thymine, uracil?

A

cytosine is deaminated to produce uracil

uracil is methylated to produce thymine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Differentiate between the terms nucleoside, ribonucleoside, ribonucleotide, and deoxyribonucleotide.

A

nucleoside = nitrogenous base

ribonucleoside = nitrogenous base + sugar (ribose)

ribonucleotide = nitrogenous base + sugar + 1 or more phosphate

deoxyribonucleotide = ribonucleotide with -OH at 2 position removed by ribonucleotide reductase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Write out the corresponding nucleosides and nucleotides for adenine.

A

adenine → adenosine → adenylate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Write out the corresponding nucleosides and nucleotides for guanine.

A

guanine → guanosine → guanylate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Write out the corresponding nucleosides and nucleotides for hypoxanthine.

A

hypoxanthine → inosine → inosinate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Write out the corresponding nucleosides and nucleotides for xanthine.

A

xanthine → xanthosine → xanthinate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What four compounds make up the purines?

A

adenine

guanine

hypoxanthine

xanthine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Write out the corresponding nucleosides and nucleotides for uracil.

A

uracil → uridine → uridylate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Write out the corresponding nucleosides and nucleotides for cytosine.

A

cytosine → cytidine → cytidylate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Write out the corresponding nucleosides and nucleotides for thymine.

A

thymine → thymidine → thymidylate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What three compounds make up the pyrimidines?

A

uracil

cytosine

thymine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Which form is most commonly encountered in cells — bases, nucleosides, or nucleotides?

A

nucleotides are most commonly encountered

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
How are purines primarily synthesized (i.e. what form do they assume)?
synthesized as **inosine monophosphate (IMP)**, an example of a _ribonucleotide monophosphate_ (rather than free base)
26
What are the carbon/nitrogen sources to form the purine ring?
glycine aspartate glutamine formyl-tetrahydrofolate
27
Write out the equation of the first step of purine synthesis.
glutamine + PRPP → phosphoribosylamine + glutamate + PPi
28
What enzyme catalyzes the first dedicated step of purine synthesis?
PRPP amidotransferase
29
Describe the reversibility of the first dedicated step of purine synthesis.
irreversible, because of hydrolysis of pyrophosphate bond
30
What is the second step of purine synthesis?
phosphoribosylamine → formation of first 5-membered ring → formation of second 6-membered ring → **inosine monophosphate**
31
Inosine monophosphate is a common precursor for which two compounds?
adenosine monophosphate (an adenylate) guanosine monophosphate (a guanylate)
32
How is IMP converted to AMP?
replace the carbonyl group of IMP with an amino group
33
The net synthesis of AMP from phosphoribosylamine consumes how many phosphates?
_4 phosphates consumed:_ 2 to make the 5-membered ring 1 to make the 6-membered ring (i.e. form IMP) 1 to replace IMP C=O group w/ NH2 (i.e. form AMP)
34
How is IMP converted to GMP?
add C=O to form XMP then add NH2 to form GMP
35
The net synthesis of GMP from phosphoribosylamine consumes how many phosphates?
_5 phosphates consumed:_ 2 to make the 5-membered ring 1 to make the 6-membered ring (i.e. form IMP) 2 for IMP → XMP → GMP
36
How are the syntheses of AMP and GMP kept in balance?
_reciprocal regulation:_ AMP synthesis requires GTP and is feedback-inhibited by AMP GMP synthesis requires ATP and is feedback-inhibited by GMP
37
AMP and GMP reciprocally regulate their syntheses. However, what happens if both AMP and GMP levels are high?
IMP (the precursor) will be degraded and excreted as uric acid instead of making more AMP/GMP
38
How is purine synthesis enzymatically regulated?
_control of glutamine-PRPP amidotransferase:_ * binding of substrate (PRPP) → conformational change in enzyme → increases activity * enzyme is allosterically feedback-inhibited by purines
39
A defect in the feedback inhibition of glutamine-PRPP amidotransferase results in
_gout:_ faulty feedback inhibition → overproduction of purines → increased uric acid formation
40
What are salvage reactions?
reusing bases or nucleosides to reform nucleotides
41
What are the two purine salvage enzymes?
hypoxanthine/guanine phosphoribosyltransferase (HPRT) adenine phosphoribosyltransferase (APRT)
42
What are the reactions catalyzed by hypoxanthine/guanine phosphoribosyltransferase (HPRT)?
hypoxanthine + PRPP → IMP + PPi guanine + PRPP → GMP + PPi
43
What is the reaction catalyzed by adenine phosphoribosyltransferase (APRT)?
adenine + PRPP → AMP + PPi
44
What is Lesch-Nyhan syndrome?
a deficiency of the hypoxanthine/guanine phosphoribosyltransferase (HPRT) enzyme
45
What is the clinical result of Lesch-Nyhan syndrome?
accumulation of hypoxanthine and guanine → degraded → high uric acid levels
46
What is the presentation of Lesch-Nyhan syndrome? (2)
severe neurological defects self-injurious behavior
47
What is the inheritance pattern of Lesch-Nyhan syndrome?
X-linked recessive
48
How are nucleotides converted to nucleosides?
using **5' nucleotidases**: e.g. AMP → adenosine + Pi
49
How are nucleosides converted to bases?
by **nucleoside phosphorylases**: e.x. guanosine + Pi → guanine + ribose-5-phosphate
50
(T/F) Adenylate cannot be directly converted to guanylate.
**True**. Conversion must go through IMP.
51
(T/F) Adenine can be deaminated.
**False.** Adenine cannot be deaminated.
52
List the steps in the conversion of hypoxanthine to uric acid.
hypoxanthine → [oxidation via xanthine oxidase] → xanthine → [oxidation via xanthine oxidase] → uric acid
53
How is gout treated?
with allopurinol, a hypoxanthine analog that acts as a suicide substrate of xanthine oxidase
54
What is the relationship between guanine and xanthine?
guanine can be **deaminated** to form xanthine
55
Draw out the overall pathway(s) of purine synthesis/degradation.
56
What is an important difference in the early synthesis of pyrimidines versus purines?
pyrimidines are synthesized as free bases, not bound to a sugar + phosphate (as is the case for purines)
57
What are the initial products of pyrimidine nucleotide synthesis?
orotate → **orotidylate** (a.k.a. orotidine monophosphate) [*precursor pyrimidine*] → other pyrimidines
58
Draw a diagram that shows the origins of the carbons and nitrogens in a pyrimidine ring.
59
What is the first step in pyrimidine synthesis?
synthesis of carbamylphosphate
60
What enzyme catalyzes the first step of pyrimidine synthesis?
carbamylphosphate synthetase II (CPS2)
61
How does CPS2 in pyrimidine synthesis differ from CPS1 in ureagenesis? (3)
CPS2: _cytosolic_ uses _glutamine_ as a nitrogen source does _not_ require N-acetylglutamate as an activator
62
What is the second step of pyrimidine synthesis?
combining carbamylphosphate + aspartate
63
What catalyzes the second step of pyrimidine synthesis?
aspartate transcarbamylase (ATCase)
64
What is the third step of pyrimidine synthesis?
dehydration reaction that closes ring → formation of **dihydroorotate**
65
Describe how the enzymes that catalyze the first three steps of pyrimidine synthesis are encoded.
CPS2, ATCase, and dihydroorotase are encoded by **CAD**, a single polypeptide
66
What enzyme catalyzes the third step of pyrimidine synthesis?
dihydroorotase
67
After dihydroorotate is formed after the first 3 steps of pyrimidine synthesis, what further processing does it undergo?
dihydroorotate → [dehydrogenation] → orotate → [ribose/phosphate transfer] → orotidylate → [decarboxylation] → urdiylate monophosphate (UMP)
68
List out the overall intermediates in pyrimidine synthesis.
carbamyl phosphate → some ring-like structure → dihydroorotate (closed ring) → orotate → orotidylate → uridylate monophosphate
69
What catalyzes the conversion of dihydroorotate to UMP?
dihydroorotate dehydrogenase UMP synthase (catalyzes orotate → orotidylate *and* orotidylate → UMP)
70
How is cytidine synthesized?
add amino group to UTP (addition must occur at nucleoside triphosphate level)
71
What is the nitrogen source in cytidine synthesis?
glutamine
72
How is pyrimidine nucleotide synthesis regulated?
_via CPS2_: inhibited by UTP activated by PRPP
73
How are pyrimidine bases salvaged to reform nucleotides?
uracil + PRPP → UMP + PPi (catalyzed by _UMP synthase_)
74
What enzyme synthesizes all four deoxyribonucleotides?
ribonucleotide reductase
75
Deoxyribonucleotide synthesis requires what cofactor?
requires NADPH for reducing power
76
What are the substrates for the ribonucleotide reductase reaction?
A**D**P, G**D**P, C**D**P, U**D**P
77
What is the major inhibitor of ribonucleotide reductase?
dATP
78
Thymidine, a nucleoside, can exist only in what nucleotidic form?
only exists as a deoxyribonucleotide
79
How is deoxythymidylate synthesized? (2)
UDP → [ribonucleotide reductase] → dUDP → dUMP → [thymidylate synthase] → dTMP *or* dCMP → [deamination] → dUMP → [thymidylate synthase] → dTMP
80
What supplies the methyl group of thymidine?
5,10-methylenetetrahydrofolate
81
What is the significance of 5,10-methylenetetrahydrofolate in terms of deoxyribonucleotide synthesis and cancer therapy?
the 5,10-methylenetetrahydrofolate reaction is the main target of **methotrexate** and **antifolates** → reduces dTMP synthesis → inhibits cell division
82
What compounds are released when pyrimidines are degraded?
beta-amino acids CO2 ammonia
83
Write out the pathway of uracil degradation. (3)
uracil → dihydrouracil → beta-alanine
84
Write out the pathway of thymine degradation.
thymine → dihydrothymine → beta-aminoisobutyric acid
85
How does the oxidation of allopurinol alleviate gout?
allopurinol → [oxidation] → oxypurinol, which can't be further oxidized by xanthine oxidase because of the position of the nitrogen, so it stops xanthine oxidase activity
86
Differentiate between xanthine and hypoxanthine in terms of solubility.
hypoxanthine = highly soluble xanthine = not soluble
87
Allopurinol can treat gout by inhibiting xanthine oxidase. What is another pathway/mechanism by which allopurinol can treat gout? (4)
allopurinol → [HPRT enzyme] → allopurinol ribonucleotide → allosterically inhibits PRPP synthetase/glutamine-PRPP amidotransferase → decreases overall purine synthesis
88
What are antimetabolites?
structural analogs of bases or nucleotides
89
Write out the pathway of 6-mercaptopurine (6MP) action.
azathioprine → 6MP → [HPRT enzyme] → 6MP ribonucleotide → feedback inhibition of glutamine-PRPP amidotransferase → inhibition of purine synthesis
90
What inactivates 6-mercaptopurine?
xanthine oxidase
91
Write out the pathway of 5-fluorouracil (5FU) action.
5FU → 5FU ribonucleotide triphosphate (5FUTP) → incorporated into mRNA → inhibits maturation of m/rRNA
92
What inhibits thymidylate synthase?
FdUMP
93
Write out the pathway of cytosine arabinoside (AraC) action. (4)
AraC, a nucleoside → Ara-CTP, a nucleotide → incorporated into DNA instead of CTP → blocks DNA synthesis
94
Why isn't methotrexate used to treat gout?
too toxic
95
What is a side effect of methotrexate treatment?
reduction in synthesis of methionine, causing homocysteine to accumulate (homocystinuria)
96
What is leukovorin?
formyl-THF that is more stable in air and used to "rescue" normal cells following methotrexate treatment
97
What is acyclovir?
inactive analog of GMP that functions as an antiviral agent
98
What is aminopterin?
a drug not used today that has similar effects to methotrexate
99
What is the active form of acyclovir?
acyclovir triphosphate
100
Write out the pathway of acyclovir action.
acyclovir → [phosphorylated in infected cells by thymidine kinase] → acyclovir triphosphate → inhibits DNA synthesis
101
Describe the function of nucleotide analogs azidothymidine (AZT) and dideoxyionsine (ddI).
used to treat HIV because of ability to inhibit reverse transcriptase
102
Describe the use of ganciclovir.
used to treat cytomegalovirus (CMV) infections
103
Describe the use of ribavirin. (2)
used to treat respiratory syncytial virus (RSV) used to treat hep C infections

Tissues (23 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions