Nucleotide Metabolism (complete) Flashcards
1
Q
Which bases are purines
A
Adening
Guanosine
2
Q
which bases are pyrimidines
A
Cytosine
thymine
Uracil
3
Q
what is the structure of the pyrimidines
A
an individual 6 membered ring
4
Q
what is the structure of purines
A
a 2 membered ring with an attached 5 membered ring
5
Q
how do you differentiate between Adenine and Guanosine
A
Adenine has a NH2
Guanine has a carbonyl
6
Q
how do you differentiate between Cytosine, thymine, and uracil
A
Cytosine has NH2
thymine has a methyl group
Uracil has neither
7
Q
- Nucleotides are only involved in RNA and DNA synthesis
a. True
b. False
A
False
8
Q
- A nucleoside is
a. A nucleobase
b. A nucleobase and a ribose sugar
c. A nucleobase, a ribose sugar and a phosphate group
d. A nucleobase, a ribose sugar, a phosphate group and acetyl CoA
A
B
9
Q
- Purine biosynthesis regulated by:
a. AMP,
b. ADP
c. IMP
d. GMP
e. All of the above
A
E
10
Q
- Which is the final step in the pathway for pyrimidine biosynthesis
a. UMP
b. CMP
c. TMP
d. TTP
A
B
11
Q
- 5-fluorouracil is an inhibitor of
a. purine bio synthesis
b. pyrimidine biosynthesis
c. thymidine synthesis
d. Adenosine synthesis
A
C
12
Q
- Another name for an anti-metabolite is:
a. Anti-toxin
b. Anti-freeze
c. Inhibitor
d. Allosteric modifier
A
Inhibitor
13
Q
- Ribonucleotide Reductase activates the tyrosine radical with
a. Iron cofactor
b. Copper cofactor
c. NAD cofactor
d. Folate cofactor
A
A
14
Q
What are the functions of nucleotides
A
Energy for metabolism (ATP) Enzyme cofactors (NAD+) Signal transduction (cAMP)
15
Q
what are the functions of nucelic acids
A
Storage of genetic info (DNA)
transmission of genetic info (mRNA)
processing genetic info (ribozymes)
protein synthesis (tRNA and rRNA)
16
Q
What is a nucleobase
A
nitrogenous base (A, T, U, C, G)
17
Q
What is a nucleoside
A
nitrogenous base and a pentose (the sugar)
18
Q
What is a nucleotide
A
nitrogenous base, pentose, and phosphate (1, 2, or 3)
19
Q
in de novo biosynthesis of purines are the bases and ribose made seperately and then put together
A
no, the base is synthesized while attached to the pentose
20
Q
what is the pentose used in DNA and RNA
A
ribose
21
Q
what amino acid provides most amino groups for newly made nucleotides
A
Gln (glutamine)
22
Q
what is the precursor for purines
A
glycine (gly)
23
Q
what is the precursor for pyrimidines
A
Asp (aspartic acid)
24
Q
What things contribute to the formation of a purine
A
aspartate (N) CO2 (C) formate (2-Cs) glycine (C=C-N) glutamine (2-Ns)
ACFGG
25
what does de novo biosynthesis of purines begin with
PRPP
26
in the de novo biosynthesis of purines what does PRPP interact with
Gln (adds an N)
27
after PRPP has reacted with Gln in de novo biosynthesis what does that molecule interact with
Gly (adds C=C--N)
28
What is the first intermediate in de novo biosynthesis of purines that has a full purine ring
inosinate (IMP)
29
what things can by synthesized from IMP
Adenine and Guanine
30
How does inosinate (IMP) get converted to Adenylate (AMP)
1. inosinate + aspartate and GTP = adenylsuccinate
| 2. Adenylsuccinate + Fumerate = adenylate
31
how does inosinate (IMP) get converted to Guanylate (GMP)
1. inosinate + H2O and NAD+ = xanthylate (XMP)
| 2. XMP + Gln and ATP = Guanylate
32
What are the enzymes required to turn IMP into AMP
1. adenylosuccinate synthetase
| 2. adenylosuccinate lyase
33
what are the enzymes required to turn IMP into GMP
1. IMP dehydrogenase
| 2. XMP glutamine amidotransferase
34
What are the five major mechanisms of regulation of purine biosynthesis
1. glutamine-PRPP amidotransferase is inhibited by IMP, AMP, GMP
2. IMP dehydrogenase inhibited by GMP
3. Adenylosuccinate synthetase inhibited by AMP
4. GTP limits conversion of IMP to AMP, ATP limits conversion of IMP to GMP
5. PRPP synthesis is inhibited by ADP and ADP
35
What inhibits the first enzyme in de novo biosynthesis of purines
IMP, AMP, GMP
| the products of de novo biosynthesis of purines
36
What is the first enzyme in de novo biosynthesis of purines
glutamine- PRPP amidotransferase
37
What inhibits the enzyme IMP dehydrogenase, and that prevents the synthesis of what
GMP inhibits IMP dehydrogenase
| that prevents the formation of XMP (and thus GMP)
38
what inhibits the enzyme adenylosuccinate synthetase, and that prevents the synthesis of what
AMP inhibits adenylosuccinate
| that prevents the formation of adenylosuccinate ( and thus AMP)
39
What effect does GTP have on de novo biosynthesis
it limits the conversion of IMP to AMP
40
what effect does ATP have on de novo biosynthesis
it limits the conversion of IMP to GTP
41
What inhibits the formation of PRPP
ADP and GDP
42
what is a main way that purine and pyrimidine biosynthesis differ
in purine biosynthesis the purine ring is made onto the ribose
in pyrimidine biosynthesis the pyrimidine ring is made, then attached to the ribose
43
what is the first step in biosynthesis of pyrimidines
Asp and N-carbamoylphosphate
44
what is the enzyme that catalyzes the Asp and N-carbamoylphosphate reaction that begins de novo biosynthesis of pyrimidines
ATCase (aspartate transcarbamoylase)
45
what is the main intermediate of pyrimidine synthesis, the one that is made first, and from there you make all of the others
UMP
46
how do you get from UMP to CTP
UMP is converted to UTP, then UTP is converted to CTP
47
does TMP come from UMP or CTP
both
48
how do you get TMP from UMP
UMP --> UDP --> dUDP --> dUTP --> dUMP -->dTMP
49
how do you get TMP from CTP
CTP --> CDP --> dCDP --> dCTP --> dUTP --> dUMP --> dTMP
50
How is de novo pyrimidine synthesis regulated
CTP (the end product) inhibits aspartate trans carbamoylase (the first enzyme)
ATP accelerates aspartate carbamoylase
51
what inhibits de novo pyrimidine synthesis
CTP
52
what accelerates de novo pyrimidine synthesis
ATP
53
what is the enzyme that helps convert dUMP to dTMP
thymidylate synthase
54
what does the conversion of dUMP to dTMP by thymidylate synthase create (though indirectly)
tetrahydrofolate (THF)
55
in dUMP and dTMP and all of those things with the d, what does the d stand for
Deoxygenized versions of those molecules
56
What happens to levels of TMP when you have low levels of folic acid
with low levels of folic acid you can't turn UMP into TMP
57
what happens to the DNA when you have low levels of folic acid, and thus low levels of TMP
UMP can't be converted to TMP so Uracil gets put into the DNA instead of thymine
58
What happens to DNA with uracil in it (this happens with a lack of folic acid, and thus low levels of TMP)
repair mechanisms remove the uracil by creating strand breaks that affect the structure and function of DNA (this is associated with cancer, heart disease, and neurological impairment)
59
Why is THF a good target for cancer treatment
because if you inhibit the thymidylate synthase in targeted cancer (causing its DNA to be altered)
60
what is another name for an antimetabolite
an inhibitor
61
what are antifolates
drugs that block the action of folate
62
what are the two main antifolates important to dTMP production
fluorouracil
| methotrexate
63
What does the anti-folate drug fluorouracil do
it is converted into FdUMP which inhibits thymidylate synthase
64
what does the anti-folate drug methotrexate do
inhibits dihydrofolate reductase, this is what makes THF (competitive inhibitor)
65
what is the difference between competitive inhibitors and suicide inhibitors
competitive inhibitors bind to enzymes temporarily and block it from binding to its usually substrate, they come off and the enzyme is ready to bind to its substrate
suicide inhibitors bind to enzymes permanently, so that it will never bind to its substrate again
66
What does ribonucleotide reductase do
it initiates radical chemistry and takes the 2' OH group and puts a 2' H group
67
are there multiple pathways that activate ribonucleotide reductase
yes
68
why are there multiple ways to activate ribonucleotide reductase
because it is such an important enzyme that if one pathway shuts down there has to be another way to activate it or we will suffer serious consequences
69
what is the structure of ribonucleotide reductase
it is a tetramer
70
What are the substrates of ribonucleotide reductase
ADP
UDP
CDP
GDP
71
What are the products of ribonucleotide reductase
dATP
dUDP
dCDP
dGDP
72
What things regulate ribonucleotide reductase
ATP (activates it)
dATP (deacitvates it)
low amounts of a certain NTP can make the ribonucleotide reductase synthesize more of that certain NTP
73
what happens in the salvage pathway
free bases react with PRPP to reform nucleotides
74
When purines are degraded what is the end product
uric acid
75
how does AMP get converted into Uric acid
AMP --> IMP --> hypoxanthine --> xanthine --> uric acid
76
how does GMP get converted into uric acid
GMP --> Guanine --> xanthine --> uric acid
77
When pyrimidines are degraded what are the end products
Succinyl-CoA (used in Citrate cycle)
| NH4 (then to urea)
78
What causes Lesch-Nyhan syndrome
overproduction of uric acid
79
who is mostly affected by Lesch-Nyhan syndrome
males
80
what are the characteristics of Lesch-Nyan syndrome
neurological and behavioral abnormalities
gouty arthritis
uric acid accumulation in the kidney and bladder
involuntary muscle movements
people can't walk
self injury is most common and distinctive
81
what is orotic aciduria
the excessive secretion of orotic acid in the urine
82
what does orotic aciduria cause
a form of anemia and mental and physical retardation
83
what type of anemia is associated with orotic aciduria
megaloblastic anemia
84
the disturbance of what pathway leads to orotic acidura
the pyrimidine synthesis pathway
85
how is orotic aciduria treated
by administering CMP and UMP
