Moyzis Flashcards
(180 cards)
0
Q
Name the purines
A
Adenine and Guanine
1
Q
About what mass of AA is used for protein synthesis in a day? For other molecules?
A
400 g/day; 30 g/day
2
Q
Which nitrogenous bases have two rings?
A
Purine
3
Q
Name the pyrimidines
A
Cytosine, Uracil, Thymine
4
Q
Which nitrogenous bases have a single ring?
A
Pyrimidine
5
Q
Which is more stable ribose or 2-deoxyribose?
A
2-deoxyribose
6
Q
What are nucleosides?
A
Pentose sugar plus base
7
Q
What is responsible for the negative charge associated with DNA?
A
Phosphate groups
8
Q
How do we name nucleotides?
A
Ribonucleoside 5’-mono/di/triphosphate
E.g. Adenosine 5’-triphosphate
9
Q
Nucleotides are?
A
Composed of a nitrogenous base, a pentose monosaccharide, and one/2/3 phosphate groups
10
Q
T or F: Donated atoms of a nitrogenous base are added to a preformed ribose 5’-phosphate
A
T
11
Q
Purine rings contain atoms donated from?
A
Formate, Glutamine (Amide groups), Aspartate, Glycine, and Carbon dioxide
12
Q
What is the first step of purine synthesis?
A
Ribose 5-phosphate is made into 5-Phosphoribosyl-1-pyrophosphate (PRPP)
13
Q
PRPP enzyme?
A
PRPP synthetase. Needs magnesium ion and ATP
14
Q
How is PRPP synthetase regulated?
A
Positive: Inorganic phosphate
Negative: Purine ribonucleotides (end product inhibition)
15
Q
What is PRPP made into?
A
5’-Phosphoribosylamine; made by Glutamine phosphoribosyl pryrophosphate amidotranferase; consumes Glutamine and Water Releasing Glutamate and Pyrophosphate. In presence of magnesium
16
Q
What step is the commit step for purine synthesis?
A
PRPP to 5’-Phosphoribosylamine
17
Q
What is the parent purine nucleotide?
A
Inosine monophosphate (takes 4 ATP to make)
18
Q
How many ATP are required to make IMP?
A
4 ATP
19
Q
What is the mechanism of sulfonamides?
A
Block synthesis of folic acid. Since purine synthesis requries THF (a folic acid derivative) as a coenzyme, the sulfa drugs inhibit this pathway. Doesnt harm human cells since we just eat folate
20
Q
T or F: Humans can synthesize folic acid
A
F
21
Q
What is the mechanism of methotrexate?
A
Structural analog to folic acid used in cancer. Interferes with nucleotide synthesis. Hurts healthy cells too like bone marrow, hair follicles, GI tract
22
Q
What energy source is needed to make AMP?
A
GTP
23
Q
What energy source is needed to make GMP?
A
ATP
24
What inhibits IMP to AMP pathway?
AMP levels
25
What inhibits IMP to GMP pathways?
GMP levels
26
What is mycophenolic acid?
A potent reversible inhibitor of IMP dehydrogenase which prevents GMP production (promising in graft rejection prevention). Deprives rapidly producing cells of a key nucleic acid
27
What is the function of base-specific nucleoside monophosphate kinases?
Converts AMP and ATP to ADP and back. Balances M,D,T forms
28
What does adenylate kinase do?
Balances AMP, ADP, and ATP levels
29
What are nucleoside diphosphate kinases?
Converts between di and tri forms only
30
What is the source of phosphate in the nucleoside phosphate conversions?
ATP almost exclusively due to high levels
31
T or F: The pyrimidine ring is made before being attached to the ribose 5-phosphate
T; this is distinct to the piecewise method for purines
32
What are the sources for the pyrimidine ring?
Glutamine, carbon dioxide, and aspartic acid
33
What is the first step of pyrimidine synthesis?
Formation of carbamoyl phosphate from Glutamine, HCO3-, and 2 ATP via Carabmoyl phosphate synthetase II to produce carabmoyl phosphate, glutamate, 2 ADP and 1 Pi
34
What enzyme makes carbamoyl phosphate?
Carbamoyl phosphate synthetase
35
What regulates carabmoyl phosphate synthetase?
Negative: UTP
Positive: ATP and PRPP
36
Carbamoyl phosphate is converted to what first ring form?
Dihydroorotate
37
T or F: The first three steps of pyrmidine synthesis is catalyzed by three different domains on the same polypeptide
T
38
T or F: Enzymes in pyrimidine synthesis are from mitochondria genes
T
39
Dihydroorotate is made into?
Orotate
40
Orotate is made into?
OMP via PRPP
41
OMP is made into?
UMP (Uridine 5'-monophosphate)
42
T or F: Dihydroorotate is made into OMP and OMP to UMP by the same protein with different domains
T
43
What is orotic aciduria?
Orotic acid in urine due to genetic defect in the last two steps
44
How is UTP made into CTP?
Via CTP synthestase and ATP, with glutamine to glutamate as the source of nitrogen
45
What is the source of nitrogen for UTP to CTP?
Glutamine
46
What is the parent molecule for pyrimidines?
UMP
47
How is 2'-deoxyribonucleotide formed?
Via ribonucleotide reductase
48
What is the structure of ribonucleotide reductase?
Two identical B1, Two identical B2 subunits which are specific for ADP, GDP, CDP, and UDP
49
Describe the allosteric activity of Ribonucleotide reductase
Binding of dATP inhibits enzyme and prevents reduction of any NDPs effectively preventing DNA syntehsis
50
What controls the substrate specificity of ribonucleotide reductase?
Binding of NTPs to a substrate site
51
What is adenosine deaminase deficiency?
Excess dATP which prevents DNA synthesis
52
How is dTMP made?
From dUMP via thymidylate synthetase
53
What is the mechanism of 5-fluorouracil?
Thymine analog that inhibits thymidylate synthase as an antitumor agent. 5-fluorouracil to 5-FdUMP which is permanent bound.
54
What is the "suicide" inhibitor?
5-fluorouracil
55
dUMP is made to dTMP by the oxidation of what molecule?
THF (tetrahydrofolate) to dihydrofolate (DHF)
56
How is DHF reduced?
Via dihydrofolate reductase to THF
57
T or F: Methotrexate inhibits both purine synthesis as well as dUMP to dTMP
T
58
How does methotrexate inhibit pyrimidine synthesis?
Methotrexate inhibits dihydrofolate reductase (DHF to THF) which prevents dUMP to dTMP
59
How are purine nucleotides degraded?
In the small intestine into uric acid
60
What is gout?
Excess uric acid in the blood
61
How are pyrimidine nucleotides degraded?
Opened and degraded to beta-alanine and beta-aminoisobutyrate which are precursors for acetyl-CoA and succinyl-CoA respectively
62
How is uric acid produced?
Amino is removed from AMP to IMP. IMP and GMP are converted to inosine and guanosine. Inosine and guanosine are converted to bases. Guanine is deamined to xanthine. Hypoxanthine is oxidized to xanthine.
Xanthine is oxidized to uric acid
63
What is guanine deaminated to?
Xanthine
64
What is inosine converted to?
Hypoxanthine
65
What does allopurinol do?
Prevents conversion of xanthine to uric acid
66
T or F: Adenine deaminase deficiency has been treated successfully by gene therapy
T
67
What enzyme does allopurinol inhibit?
Xanthine oxidase
68
What two enzymes are responsible for purine salvage?
Adenine Phosphoribosyltransferase (APRT) and hypo-xanthine-guanine phosphoribosyltransferase (HPRT)
69
What cofactors do APRT and HPRT need?
PRPP (taken to pyrophosphate)
70
T or F: Purine salvage is irreversible
T
71
HPRT takes hypoxanthine to?
IMP
72
HPRT takes guanine to?
GMP
73
APRT takes adenine to?
AMP
74
What is Lesch-Nyhan syndrome?
X-chromosome linked recessive disorder leading to complete deficency of HPRT leading to increased PRPP and decreased IMP and GMP. Uric acid is highly produced leading to severe gout and self-mutiliation
75
What is another name for epinephrine?
Adrenalin
76
Name three catecholamines
Dopamine, norephinephrine, epinephrine
77
The catecholamines do?
Degredation of glycogen and increase blood pressure and heart output
78
What is serotonin?
5-hydroxytryptamine and plays role in pain, affective disoreders, regulation of sleep, temperature, and blood pressure
79
The catecholamines are derived from what ?
Tyrosine
80
What AA can be made into tyrosine?
Phenylalanine
81
Tyrosine is hydroxylated to?
DOPA
82
DOPA is decarboxylated to?
Dopamine
83
Dopamine can be hydroxylated to?
Norepinephrine
84
What are MAOs?
Oxidatively demainate catecholamines (monoamine oxidases)
85
What are MAO inhibitors?
Block MAO enzyme raising NT levels (used in anti-depression meds)
86
What NT is given to Parkinson's patients?
L-dopa
87
What is methylphenidate?
Blocks reuptake by dopamine transporters leading to synapse stimulus
88
What AA is the progenitor to serotonin?
Tryptophan
89
How is Tryptophan made into serotonin?
Hydroxylated and then decarboxylated
90
Low levels of serotonin is associated with?
depression
91
How to paxil and prozac work?
Block serotonin transporters and increase synaptic serotonin levels
92
T or F: Phenylalanine and Tryptophan are essential AA
TRUE (crazy)
93
Nucleotides are composed of?
Nitrogenous base, pentose monosaccharide, and 1/2/3 phosphate groups
94
How do T and U differ in structure?
T has a methyl group
95
What is a nucleoside?
Pentose and base
96
What are the five nucleoside names?
Adenosine, guanosine, cytidine, uridine, thymidine
97
What inhibits PRPP synthetase?
AMP, GMP, and IMP
98
What is the committed step in purine biosynthesis?
PRPP synthetase taking Ribose 5-phosphate to PRPP
99
What is another name for PRPP synthetase?
Glutamine phosphoribosyl pryophosphate amidotransferase
100
What controls the rate of reaction for production of PRPP?
PRPP levels (far below Km so small changes give proportional change in rate of reaction)
101
How many ATP are required to take PRPP to IMP?
4
102
What folic acid analog is required in two steps of purine synthesis?
N10-formyltetrahydrofolate
103
What does trimethoprim do?
Folate analog that selective inhibits bacterial dihydrofolate reducatase
104
T or F: AMP and GMP production are self-inhibiting (feedback)
T
105
T or F: MPA is uncompetitive inhibitor
T
106
T or F: Interconversions of phosphate lengths for nucleotides are all powered by ATP
T
107
Which are more specific: Base-specific nucleoside monophosphate kinases or nucleoside diphosphate kinase
First one, however second one only works on DP nucleosides
108
What is the source of ribose 5-phosphate in pyrimidine synthesis?
PRPP
109
What two AA are needed for both purine and pyrimidine synthesis?
Glutamine and aspartic acid
110
What is the regulated step of pyrimidine synthesis?
Synthesis of carbamoyl phosphate from glutamine and CO2 via carbamoyl phosphate synthetase (CPS) II.
111
What regulates CPS II?
Negative: UTP
Positive: ATP and PRPP
112
T of F: CPS requires biotin cofactors
F
113
Carbamoyl phosphate is made into?
Carbamoylasparate by asparate transcarbamoylase
114
Where is orate enzyme located?
Inner mitochondrial membrane
115
What three enzymes are on the same multicatalytic polypeptide in pyrimidine synthesis?
CPS II, aspartate transcarbamoylase, dihydroorotase
116
Orotate is made into?
OMP by orotate phosphoribosyl transferase converting PRPP to PP
117
OMP is made into?
UMP by OMP decarboxylase losing CO2
118
T or F: OMP decarboxylase and Orotate phosphoribosyl transferase are on the same protein
T
119
UTP is made to CTP by?
CTP synthetase
120
What provides the nitrogen in the UTP to CTP step?
Glutamine
121
2'-deoxyribonucleotides are produced from what two things?
Ribonucleodtide diphosphates and ribonucleotide reductase (enzyme)
122
What happens when dATP binds to allosteric sites on ribonucleotide reductase?
Stops overall catalytic activity (adenosine deaminase deficiency leads to toxicity)
123
dUMP is converted to what by what enzyme?
dTMP by thymidylate synthetase
124
What donates methyl group for dUMP to dTMP?
THF which is oxidized to DHF
125
T or F: Methotrexate affects both purine and dUMP to dTMP synthesis
T
126
T or F: Dietary DNA is used to a large extent in synthesis of cellular DNA
F
127
Dietary purines are converted to...
Uric acid by intestinal mucosal cells
128
Dietary pyrimidines are made into...?
Opened and degraded into soluble products releasing ammonia and CO2
129
The rate limiting enzyme in DOPA production is?
tyrosine hydroxylase
130
What inactivates catecholamines besides MAOs?
COMTs catechol-O-methyl-transferase
131
Approximate size of genome of human? Percent coding proteins? Repetitive? Gene number?
3000 Mb, 1.5 percent, >50 percent, ~25,000
132
Average exon, size, polypeptide for a gene?
9, 122 bp, 500 AA
133
RNA and DNA are degraded to what and where?
Oligonucleotides in the small gut
134
What happens to oglionucleotides in the gut?
Absorption into intestinal mucosal cells to be degraded into free bases
135
Hyperuricemia is associated with what degredation pathway?
Purine degradation leading to uric acid
136
What does idiopathic mean?
No known cause
137
What is alternative splicing?
mRNA is spliced into different processed forms introns/exons
138
T or F: Human exons are comparitively short
T
139
T or F: Human introns are short comparitively
F; they are long
140
T or F: Larger genes are more likely to be mutated
T (doesn't mean deadly, in fact most small genes are deadly if mutated)
141
T or F: Human genes have many copies
T
142
What percentage of genes have known function?
Only 50 percent!
143
Describe what is meant about genes within genes?
Sense and Anti-sense strands have different genes on them in the same gene (exons)
144
Deletion/mutation in NF1 causes?
Neurofibromatosis
145
50% of the genome is repetitive, what makes this up?
Tandem repeats at centromeres and telomeres as well as Interspersed repeats (Alu and L1)
146
Tandem repeats are often found near what on the chromosome?
Centromere (very heterochromatic)
147
What is the sequence of human telomere?
TTAGGG
148
Telomerase solves what problem in regards to DNA replication?
End replication problem
149
What happens to the telomere with age?
Shortens
150
What is dyskeratosis congenita?
Mutation in RNA portion of telomerase
151
What is the size and count of Alu?
300 bp, more than a million copies
152
What is the size and count of L1?
7kb, more than 100,000 copies (many truncated)
153
T or F: Alu and L1 are retroposons
T (move through reverse transcriptase mechanism)
154
Describe the chain reaction of L1?
Brings its own promoter and codes for endonuclease and reverse transcriptase so they are coded in again and again
155
T or F: L1 genes are used to fill DSB
T
156
T or F: L1 Reverse Tx can be used to make copies of any gene
T (pseduogene)
157
T or F: Movement of transposons is a major source of new mutation in humans
T
158
What is VJ rejoining?
A major source of diversity in antibodies due to transposon recombinase
159
What is genomic imprinting?
Maternal or Paternal allele is silenced by methylation
160
T or F: Methylation is reset in the germline
T
161
T or F: Due to X-silencing, female cells are mosaics
T
162
The maternal equivalent of Prader-Willi syndrome is?
Angelman syndrome
163
What is the out of africa hypothesis?
Modern humans evolved out of Africa 50kyrs ago and migrated throughout world
164
What is the mutation rate and how is it used anthropologically?
3 x 10^-9 mutations/bp/generation, molecular clock
165
SNPs tell us?
Each SNP tells us age of DNA
166
Allele variation tells us?
Spelling of the gene are genetic markers
167
A bottleneck leads to what?
Low genetic diversity
168
Humans are not very genetically diverse because of a ?
Genetic bottleneck
169
Humans in Africa are roughly how old? Europe? Asia? America?
100 kyrs, 40kyrs, 50-70 kyrs, 15-30 kyrs
170
Roughly how many years per generation?
20 yrs
171
Which population has the greatest genetic diversity?
African populations, then Asian and European, then Americans
172
T or F: Human genome has remnants of other species like neanderthals ?
T (meaning they mated while migrating)
173
T or F: SNPs have distinct geographic bias
T
174
DRD4 7R is associated with what?
Blunted response to dopamine and is associated with ADHD (highly prevalent in the Americas, not common in Asia for example)
175
Where is lactase gene most likely found?
Populations that ate milk (europe and Middle East)
176
What is sickle cell disease?
Common in areas where malaria is common
177
What is heterozygote advantage?
Individuals with one of each allele has an advantage (sickle cell)
178
What is the disease gene? Do we have it?
We do not have genes for disease, we have altered genes that lead to disease
179
What is the genome wide association study approach?
Use of genome level examination to tell us that a functional variation must exist without telling us function. Then we can study these to see what they are
