Module 7 Flashcards
(133 cards)
1
Q
Monomeric units that make the nucleic acids DNA and RNA
A
Nucleotides
2
Q
Responsible for the storage and passage of theinformation needed for the productions of proteins?
A
Nucleic acids
3
Q
Each nucleotides consists of?
A
Pentose sugar,
Nitrogenous base
Phosphate group
4
Q
Nucleotides result from linking one or more phosphates with a nucleoside onto the 5’ end of the molecule through
A
Esterfication
5
Q
5-carbon sugar in a pentose ring form
A
Pentose sugar
6
Q
RNA contains ribose, which has a hydroxyl group in both the
A
2 and 3 position
7
Q
DNA has only a single hydroxyl group in the
A
3 position
8
Q
Lacks a 2’-OH group
A
2 deoxyribose
9
Q
Bond between adenine and deoxyribose
A
Glycosidic bond
10
Q
Nucleosides
A
dAdenosine
11
Q
Nucleotides
A
dAdenylic acid ( dAMP)
12
Q
A nitrogenous base is attached by a glycosidic bond to the __________of the nucleotide’s sugar
A
1 carbon
13
Q
Purinesconsist of linked 5-membered and 6membered rings__________ and _________) which can be found in DNA or RNA
A
Adenine A
Guanine G
5 and 6 membered rings
14
Q
Pyrimidines consist of 6-membered rings
A
Cytosine C
Thymine T
Uracil U
15
Q
Found in DNA and RNA
A
Cytosine
16
Q
Found in DNA
A
Thymine
17
Q
Found in RNA
A
Uracil
18
Q
Nitrogenous base are
A
Planar, aromatic, and heterocyclic
19
Q
Nitrogenous base derived from
A
Purine and pyrimidines
20
Q
Nitrogenous base numbering of bases are
A
Unprimed
21
Q
The sugar is linked to the base via a ___________ bond to the __________________
A
b-Nglycosidic bond
N-1 of pyrimidines
N-9 of purines
22
Q
Purine nucleosides end in
A
Sine
23
Q
Pyrimidine nucleosides end in
A
Dine
24
Q
Nucleotides are linked together by ________________ between the _________ on the sugar of one nucleotide through a phosphate molecule to the ____________ on the sugar of another nucleotide
A
Phosphodiesterase bonds
3 hydroxyl
5 hydoxyl
25
Bondsof nucleotides are broken by?
Phosphodiesterase
26
Bond between complementary nucleotide chain and normal nucleotide chain.
Hydrogen bond
27
a second messenger in response to nitric oxide during smooth muscle relaxation
cAMPand cGMP
28
Function of nucleodtides
Syhtesis of cyclic AMP and GMP
Methyl group transfer
Glycogen, bilirubin, phosphoglyceride synthesis
29
Nucleotides absorb
UV lights
30
used as antivirals and in cancer chemotherapy
Synthetic nucleotide
31
targets for cancer chemotherapy and viral disease treatment
Purine and pyrimidine synthesis
32
activated precursors in nucleic acid synthesis
Nucleoside triphosphate
33
purines are not initially synthesized as free bases–First purine derivative formed is
Inosine monophophate
34
AMP and GMP are formed from
IMP or inosine monophosphate
35
The activated sugar used is 5-phosphoribosyl-1pyrophosphate, PRPP
Inosine monophosphate
36
PRPP is generated by the action of PRPP synthetase and requires energy in the form of
ATP
37
IMP is inhibited by
ADP and GDP (Allosteric
38
First committed step of purine synthesis
IMP
39
The major site of purine synthesis is in the
Liver
40
Synthesis of the purine nucleotides begins with ____________ and leads to the first fully formed nucleotide, ________________
PRPP
| Inosine 5 moniphosphate
41
Synthesis of IMP requires
```
5ATP
2glutamine
1glycine
1Co2
1aspartate
2formate
```
42
The pathway leading to AMP requires energy in the form of
GTP
43
leading to GMP requires energy in the form of
ATP
44
Important enzyme and product in synthesis of AMP
Adenylosucinate lyase
| Fumarate
45
Important enzyme and product in synthesis of GMP
GMP syhthetase
| Glutamine and glutamate
46
The utilization of GTP in the pathway to AMP synthesis allows the cell to control the proportions of AMP and GMP to near ____________
Equivalence
47
Increase GTP
increase AMP
48
The synthesis of PRPP by PRPP synthetase is feed-back inhibited by
Purine 5 nucleotides
49
The essential rate limiting steps in purine biosynthesis occur at the
First two step of the pathway
PRPP synthetase
Amino transferase reaction
50
The amidotransferase reaction (2ndstep) catalyzed by PRPP glutamyl amidotransferase is also feed-back inhibited allosterically by
binding ATP, ADP and AMP at one inhibitory site and GTP, GDP and GMP at another
51
Increase ATP
Increase GMP
52
Increase AMP
Increase GMP
53
Increase GMP
Increase AMP
54
GTP AMP
Adenylosuccinate
55
ATP GMP
Xanthylic acid
56
Catabolism of the purine nucleotides leads ultimately to the production of ___________ which is insoluble and is excreted in the urine as __________
Uric acid
| Sodium urate crystals
57
The synthesis of nucleotides from the purine bases and purine nucleosides takes place in a series of steps known as the
Salvage pathway
58
The free purine bases, adenine, guanine, and hypoxanthine, can be reconverted to their corresponding nucleotides by
Phosphoribosylation
59
Two key transferase enzymes are involved in the salvage of purines
Adenosine phophoriboyltransferase
| hypoxanthine-guanine phosphoribosyltransferase
60
A critically important enzyme of purine salvage in rapidly dividing cells is ___________ (ADA) which catalyzes the deamination of adenosine to inosine
Adenosine deaminase
61
Deficiency in ADA results in the disorder called
Severe combined immunodeficiency
62
can also contribute to the salvage of the bases through a reversal of the catabolism pathways. However, this pathway is less significant than those catalyzed by the phosphoribosyltransferases
Purine nucleotide phosphorylases
63
The synthesis of AMP from IMP and the salvage of IMP via AMP catabolism have the net effect of deaminating aspartate to
Fumarate
64
Catabolism of purine nucleotide
purine nucleotide cycle
65
the muscle-specific isoenzyme of AMP deaminase, and deficiencies in myoadenylate deaminase lead to post-exercise fatigue, cramping and myalgias
Myoadenylate deaminase
66
Clinical problems associated with nucleotide metabolism in humans are predominantly the result of
Abnormal catabolism of purine
67
Most forms of gout are the result of _______________ or to a partial deficiency in the salvage enzyme, __________
Excess purine production
| HGPRT
68
Responsible for re-forming IMP and GMP from hypoxanthine and guanine
HGPRT and the salvage system
69
Most forms of gout can be treated by administering the antimetabolite
Allopurinol
70
Allopurinol structural analog of hypoxanthine that strongly inhibits
Xanthine oxidase
71
condition that results from the precipitation of urate (uric acid) as monosodium urate (MSU) or calcium pyrophosphate dihydrate (CPPD) crystals in the synovial fluid of the joints, leading to severe inflammation and arthritis
Gout
72
syndrome results from the loss of a functional HGPRT gene
Lesch nyhan syndrome
73
The disorder is inherited as a sex-linked trait, with the HGPRT gene on the
X chromosome q 26-27
74
Patients with this defect exhibit not only severe symptoms of gout but also a severe malfunction of the nervous system. •In the most serious cases, patients resort to selfmutilation. •Death usually occurs before patients reach their
20th year
75
most often (90%) caused by a deficiency in the enzyme adenosine deaminase (ADA
SCID
76
ADA deficiency selectively leads to a destruction of ________________, the cells that mount immune responses
B and T lymphocytes
77
In the absence of ADA, ______________ is phosphorylated to yield levels of dATP that are 50-fold higher than normal
Deoxyadenosine
78
The net effect of SCID is to inhibit __________ synthesis
DNA
79
Since lymphocytes must be able to proliferate dramatically in response to antigenic challenge, the inability to synthesize DNA seriously impairs the immune responses, and the disease is usually fatal in infancy unless special protective measures are taken
Nice to know
80
A less severe immunodeficiency results when there is a lack of __________________ another purinedegradative enzyme
Purine nucleoside phophorylase PNP
81
Glycogen storage disease that also lead to excessive uric acid production
Von gierke disease
82
Von gierke results from a dificiency in
Glucose 6 phosphatase
83
The increased availability of glucose-6phosphate increases the rate of flux through the pentose phosphate pathway, yielding an elevation in the level of ribose-5-phosphate and consequently PRPP
Nice to know
84
Pyrimidine Nucleotide Biosynthesis
1 glutamine
1 ATP
1 CO2
1 aspartate
85
carbamoyl phosphate used for pyrimidine nucleotide synthesis is derived from
Glutamine and bicarbonate within the cytosol
86
urea cycle carbamoyl phosphate derived from
Ammonia and bicarbonate within the mitochondrion
87
Urea cycle: pyrimidine
CPS 1; CPS 2
88
Carbamoyl phosphate is then condensed with aspartate in a reaction catalyzed by the rate limiting enzyme of pyrimidine nucleotide biosynthesis
Aspartate transcarbamoylase
89
UMP Synthesis Overview •2 ATPs needed: both used in first step
Transfer phosphate
| Hydrolyzed ADP and Pi
90
UMP syhtesis 2 condensation reactions
Carbamoyl aspartate
| OMP
91
Pyrimidine ring syhtesize from
Carbomyl phosphate and aspartate
92
Purine/Pyrimidine degradation are the same for ribonucleotides and deoxyribonucleotides •Biosynthetic pathways are only for ribonucleotide production •Deoxyribonucleotides are synthesized from corresponding ribonucleotides
Nice to know
93
Ribose sugar in DNA lacks hydroxyl group at
2 carbon
94
Reduction of 2’ carbon done via a free radical mechanism catalyzed by
Ribonucleotide reductase
95
a multifunctional enzyme that contains redox-active thiol groups for the transfer of electrons during the reduction reactions
Ribonucleotide reductase
96
RR is reduced in turn, by either
Thioredoxin or glutaredoxin
97
The ultimate source of the electrons is
NADPH
98
ATP ACTIVATES REDUCTION OF
CDP and UDP
99
INHIBITS REDUCTION OF ALL NUCLEOTIDES
dATP
100
STIMULATES ADP REDUCTION •INHIBITS CDP,UDP,GDP REDUCTION
dGTP
101
INDUCES GDP REDUCTION •INHIBITS REDUCTION OF CDP. UDP
dTTP
102
The dUMP is converted to dTMP by the action of
Thymidylate synthase
103
The de novopathway to dTTP synthesis first requires the use of dUMP from the metabolism of either UDP or CDP
Nice to know
104
The methyl group (recall that thymine is 5-methyl uracil) is donated by
N5 N10 methylene
105
The unique property of the action of thymidylate synthase is that the THF is converted to _________________, the only such reaction yielding DHF from THF
Dihydrofolate
106
In order for the thymidylate synthase reaction to continue, THF must be regenerated from DHF. This is accomplished through the action of
Dihydrofolate reductase
107
THF is then converted to N5,N10-THF via the action of _________________
Serine hydroxymethyl transferase
108
The crucial role of DHFR in thymidine nucleotide biosynthesis makes it an ideal target for chemotherapeutic agents such as ___________ and ____________, which are structural analogues of PABA and Folic acid
Sulfonamides
| Trimethoprim
109
cannot use exogenous folate but must synthesize it from PABA
Sulfonamide susceptible organisma
110
also useful as an antibacterial; it does not affect mammalian cells because it is about 50,000 times less efficient in inhibition of mammalian dihydrofolate reductase
Trimethoprim
111
used in cancer chemotherapy
Methotrexate
112
The salvage pathway to dTTP synthesis involves the enzyme ___________ which can use either thymidine or deoxyuridine as substrate
Thymidine kinase
113
Thymidine kinase is inhibited by
dTTP
114
The regulation of pyrimidine synthesis occurs mainly at the first step which is ctalyzed by
Aspartate trabscarbamoylase, ATCase
115
ATCase is inhibited by
CTP, UDP, UTP, and dUTP
116
multifunctional protein in mammalian cells. It is capable of catalyzing the formation of carbamoyl phosphate, carbamoyl aspartate, and dihydroorotate
ATCase
117
ATCase, and therefore the activity of CPSII, is localized to the __________ and prefers ___________ as a substrate
Cytoplasm
| Glutamine
118
The role of glycine in ATCase regulation is to act as a competitive inhibitor of the glutamine binding site
Glutamine binding site
119
As in the regulation of purine synthesis, ATP levels also regulate pyrimidine biosynthesis at the level of
PRPP formation
120
Catabolism of the pyrimidine nucleotides leads ultimately to __________(when CMP and UMP are degraded
Beta alanine
121
when dTMP is degraded catabolism of nucleotides
Beta aminoisobutyrate
122
The β-alanine and β-aminoisobutyrate serve as NH2 donors in transamination of
α-ketoglutarate to glutamate
123
which can be diverted to fatty acid synthesis
Malonyl CoA
124
which is converted to succinyl-CoA and can be shunted to the TCA cycle
Methylmalonyl CoA
125
The salvage of pyrimidine bases has less clinical significance than that of the purines, owing to the solubility of the byproducts of pyrimidine catabolism
Nice to know
126
Uracil can be salvaged to form UMP through the concerted action of
Uridine phisphorylase
| Uridine kinase
127
Formation of dTMP, by salvage of thymine requires
thymine phosphorylase and thymidine kinase
128
The salvage of deoxycytidine is catalyzed by
deoxycytidine kinase
129
Two inherited disorders affecting pyrimidine biosynthesis are the result of deficiencies in the bifunctional enzyme catalyzing the last two steps of UMP synthesis
orotate phosphoribosyl transferase and OMP decarboxylase
130
causes retarded growth, and severe anemia caused by hypochromic erythrocytes and megaloblastic bone marrow
Orotic aciduria
131
also common in orotic acidurias
Leukopenia
132
can also cause orotic aciduria because it can act as an alternate substrate and compete with orotic acid for degradation
Allopurinol
133
Orotic aciduria can be treated with
uridine and/or cytidine
