Nucleotide metabolism Flashcards
1
Q
What is the source of N1 in purine synthesis?
A
Aspartate amino group
2
Q
Which compound donates C2 and C7 in purine synthesis?
A
N10-formyl THF
3
Q
What are the sources of N3 and N9 in purine synthesis?
A
Amide group of glutamine
4
Q
Which atoms in purine synthesis are contributed by glycine?
A
C4, C5, and N7
5
Q
What is the direct source of C6 in purine synthesis?
A
CO2
6
Q
Are purine bases synthesized directly?
A
No, they are formed as ribonucleotides
7
Q
What is the precursor molecule for purine synthesis?
A
Ribose 5-phosphate
8
Q
Which organ is the major site of purine nucleotide synthesis?
A
Liver
9
Q
Which cells cannot produce purines?
A
Erythrocytes, polymorphonuclear leukocytes, and brain cells
10
Q
Which pathway produces ribose 5-phosphate?
A
Hexose monophosphate shunt
11
Q
What is the first step in purine synthesis?
A
Ribose 5-phosphate reacts with ATP to form PRPP
12
Q
Which enzyme catalyzes the committed step of purine biosynthesis?
A
PRPP glutamyl amidotransferase
13
Q
Which molecules inhibit PRPP glutamyl amidotransferase?
A
IMP, AMP, GMP
14
Q
Which molecule reacts with PRPP to form 5-phosphoribosylamine?
A
Glutamine
15
Q
Which enzyme catalyzes the conversion of PRPP to 5-phosphoribosylamine?
A
PRPP glutamyl amidotransferase
16
Q
What does phosphoribosylamine react with to form glycinamide ribotide (GAR)?
A
Glycine
17
Q
Which coenzyme is required for the formation of formylglycinamide ribotide?
A
N10-formyl tetrahydrofolate
18
Q
Which molecule donates the second amide group in purine synthesis?
A
Glutamine
19
Q
What is the function of ATP in purine ring closure?
A
Drives imidazole ring formation
20
Q
Which reaction incorporates CO2 in purine synthesis?
A
Conversion of 5-aminoimidazole ribosyl 5-phosphate to aminoimidazole carboxylate ribosyl 5-phosphate
21
Q
Does the CO2 incorporation step require biotin or ATP?
A
No
22
Q
Which molecule condenses with aminoimidazole carboxylate ribosyl 5-phosphate?
A
Aspartate
23
Q
Which enzyme cleaves fumarate in purine synthesis?
A
Adenosuccinate lyase
24
Q
Which enzyme catalyzes the final step to form inosine monophosphate (IMP)?
A
Cyclohydrolase
25
What is the parent purine nucleotide?
Inosine monophosphate (IMP)
26
Which coenzyme is essential for purine nucleotide synthesis?
Folic acid (THF)
27
Which drugs inhibit folic acid synthesis in microorganisms?
Sulfonamides
28
Why don�t sulfonamides affect humans?
Humans obtain folic acid from the diet
29
Which drug inhibits purine synthesis and is used for cancer treatment?
Methotrexate
30
Which two reactions in purine synthesis require THF?
Reaction 4 and Reaction 10
31
What is the effect of methotrexate on cells?
Inhibits DNA/RNA synthesis, causing side effects like anemia and baldness
32
Which molecule condenses with IMP to form adenylsuccinate?
Aspartate
33
Which enzyme catalyzes adenylsuccinate cleavage to form AMP?
Adenylsuccinase
34
Which cofactor is required for IMP conversion to XMP?
NAD+
35
Which molecule donates an amide nitrogen to XMP to form GMP?
Glutamine
36
Which drug inhibits both AMP and GMP synthesis?
6-Mercaptopurine
37
Which enzyme does 6-mercaptopurine inhibit in the AMP pathway?
Adenylsuccinase
38
Which enzyme does 6-mercaptopurine inhibit in the GMP pathway?
IMP dehydrogenase
39
Which enzymes convert monophosphates to di- and triphosphates?
NMP kinases and NDP kinases
40
Which molecules are salvaged in the purine salvage pathway?
Adenine, guanine, hypoxanthine
41
Which enzyme converts adenine to AMP?
Adenine phosphoribosyl transferase
42
Which enzyme converts guanine and hypoxanthine to GMP and IMP?
HGPRT
43
What is the ribose donor in the salvage pathway?
PRPP
44
Why is the salvage pathway important for erythrocytes and brain?
These cells lack de novo purine synthesis
45
Which disease is caused by a defect in HGPRT?
Lesch-Nyhan syndrome
46
What regulates purine nucleotide synthesis?
PRPP concentration
47
Which enzyme controls purine synthesis by feedback inhibition?
PRPP glutamyl amidotransferase
48
Which molecules inhibit PRPP glutamyl amidotransferase?
AMP and GMP
49
What inhibits adenylsuccinate synthetase?
AMP
50
What inhibits IMP dehydrogenase?
GMP
51
How are ribonucleotides converted to deoxyribonucleotides?
Reduction at C2 of ribose
52
Which enzyme catalyzes ribonucleotide reduction?
Ribonucleotide reductase
53
What provides reducing equivalents for ribonucleotide reductase?
Thioredoxin
54
Which enzyme regenerates reduced thioredoxin?
Thioredoxin reductase
55
What is the cofactor for thioredoxin reductase?
NADPH
56
What does lead poisoning cause?
Kidney damage and decreased uric acid excretion causing gout
57
What is the prevalence of gout?
3 per 1,000 persons
58
Which gender is mostly affected by gout?
Males
59
Which women are as susceptible to gout as men?
Post-menopausal women
60
How many types of gout are there?
Two
61
What are the two types of gout?
Primary and secondary
62
What is primary gout caused by?
Inborn error of metabolism leading to uric acid overproduction
63
What is primary gout mostly related to?
Increased purine nucleotide synthesis
64
Which enzyme's variant forms contribute to primary gout?
PRPP synthetase
65
Why do variant PRPP synthetase enzymes lead to gout?
They lack feedback control by ADP and CDP
66
What does the lack of PRPP synthetase regulation cause?
Increased purine production
67
Which enzyme involved in primary gout lacks feedback control?
PRPP glutamylamidotransferase
68
Which enzyme deficiency causes Lesch-Nyhan syndrome?
HGPRT
69
Which pathway is HGPRT involved in?
Purine salvage pathway
70
How does HGPRT deficiency increase purine synthesis?
Decreased salvage and impaired feedback regulation
71
Which purines accumulate in HGPRT deficiency?
Hypoxanthine and guanine
72
What disease is associated with glucose 6-phosphatase deficiency?
Von Gierke�s disease
73
Why does von Gierke�s disease lead to increased purine synthesis?
Increased HMP shunt activity
74
Which molecule accumulates in von Gierke�s disease?
Lactic acid
75
How does lactic acid accumulation contribute to gout?
It interferes with uric acid excretion
76
Which enzyme increases NADP+ levels, leading to purine overproduction?
Glutathione reductase
77
What does increased NADP+ stimulate?
HMP shunt
78
Which three enzymes directly regulate purine synthesis?
PRPP synthetase, PRPP glutamylamidotransferase, HGPRT
79
What is secondary gout caused by?
Increased uric acid synthesis or decreased excretion
80
Which conditions lead to increased uric acid synthesis?
Cancers, psoriasis, trauma, starvation
81
Which organ dysfunction can lead to secondary gout?
Kidney dysfunction
82
What is the normal uric acid pool size?
1,200 mg
83
What is the uric acid pool size in gout?
3,000 mg or more
84
What is the drug of choice for primary gout?
Allopurinol
85
What is allopurinol a structural analog of?
Hypoxanthine
86
Which enzyme does allopurinol inhibit?
Xanthine oxidase
87
What type of inhibition does allopurinol exhibit?
Suicide inhibition
88
What does allopurinol get converted to?
Alloxanthine
89
Why does alloxanthine inhibit xanthine oxidase?
It is a more effective inhibitor than allopurinol
90
Which compounds accumulate due to xanthine oxidase inhibition?
Hypoxanthine and xanthine
91
Why are hypoxanthine and xanthine beneficial for excretion?
They are more soluble than uric acid
92
Besides medication, what is recommended for gout treatment?
Dietary purine and alcohol restriction
93
What lifestyle change helps with gout?
Increased water intake
94
Which anti-inflammatory drug is used for gouty arthritis?
Colchicine
95
Name three other anti-inflammatory drugs used for gout
Phenylbutazone, indomethacin, corticosteroids
96
What is the cause of pseudogout?
Calcium pyrophosphate crystal deposition
97
How does pseudogout differ from gout?
Normal serum uric acid levels
98
Which enzyme is deficient in Lesch-Nyhan syndrome?
HGPRT
99
Who first described Lesch-Nyhan syndrome?
Michael Lesch and William L. Nyhan
100
Which chromosome carries the HGPRT gene?
X chromosome
101
Why does Lesch-Nyhan syndrome affect only males?
It is X-linked
102
What are the main symptoms of Lesch-Nyhan syndrome?
Gouty arthritis, mental retardation, self-mutilation
103
Which behaviors are characteristic of Lesch-Nyhan syndrome?
Biting fingers and lips
104
How does HGPRT deficiency increase purine degradation?
Accumulation of PRPP and decreased IMP/GMP
105
Does uric acid toxicity cause neurological symptoms in Lesch-Nyhan syndrome?
No
106
Does allopurinol treatment help neurological symptoms in Lesch-Nyhan syndrome?
No
107
Which enzyme deficiency causes SCID?
Adenosine deaminase (ADA)
108
Which immune cells are affected in ADA deficiency?
T-cells and B-cells
109
What does ADA deficiency lead to?
dATP accumulation
110
Why does dATP accumulation cause immunodeficiency?
It inhibits ribonucleotide reductase
111
Which enzyme deficiency impairs only T-cell function?
Purine nucleoside phosphorylase deficiency
112
What accumulates in purine nucleoside phosphorylase deficiency?
dGTP
113
What is dGTP�s effect on T-cells?
Inhibits their development
114
What is folic acid essential for?
Purine nucleotide synthesis
115
Which drug inhibits folic acid metabolism for cancer treatment?
Methotrexate
116
Why is the salvage pathway important for brain and erythrocytes?
They lack de novo purine synthesis
117
What is the final product of purine metabolism?
Uric acid
118
What is the main disorder associated with uric acid overproduction?
Gout
119
What is hypouricemia?
Serum uric acid levels <2 mg/dL
120
Which enzyme deficiency causes hypouricemia?
Xanthine oxidase deficiency
121
What accumulates in xanthine oxidase deficiency?
Xanthine and hypoxanthine
122
What condition is associated with xanthinuria?
Xanthine kidney stones
123
What is the main difference between purine and pyrimidine synthesis?
Pyrimidine ring is synthesized first, then attached to ribose
124
What are the three main precursors for pyrimidine synthesis?
Aspartate, glutamine, CO2
125
Which enzyme catalyzes the first step of pyrimidine synthesis?
Carbamoyl phosphate synthetase II (CPS II)
126
Which molecules activate CPS II?
ATP and PRPP
127
Which molecules inhibit CPS II?
UTP and UDP
128
What is the committed step in bacterial pyrimidine synthesis?
Aspartate transcarbamoylase (ATCase)
129
Which enzyme catalyzes pyrimidine ring closure?
Dihydroorotase
130
Which nucleotide is synthesized first in pyrimidine synthesis?
Orotidine monophosphate (OMP)
131
What does OMP decarboxylate to?
UMP
132
Which enzyme catalyzes UMP formation?
OMP decarboxylase
133
What is the end product of pyrimidine degradation?
?-alanine and ?-aminoisobutyrate
134
Which enzyme catalyzes the salvage of pyrimidines?
Pyrimidine phosphoribosyltransferase
135
What is orotic aciduria caused by?
Orotate phosphoribosyltransferase and OMP decarboxylase deficiency
136
What are the symptoms of orotic aciduria?
Anemia, growth retardation, orotic acid in urine
137
What is the treatment for orotic aciduria?
Uridine and cytidine supplementation
138
What causes secondary orotic aciduria?
Ornithine transcarbamoylase (OTC) deficiency
139
What happens in OTC deficiency?
Carbamoyl phosphate accumulates and increases orotic acid synthesis
140
What are nucleotide coenzymes synthesized from?
B-complex vitamins
141
Name five nucleotide coenzymes
FMN, FAD, NAD+, NADP+, Coenzyme A
