Nucleotides Flashcards
(139 cards)
0
Q
Metabolism of Xenobiotics: Phase 1 Reaction
A
Hydroxylation reactions
Enzyme: monooxygenases of cytochrome P450s
1
Q
Medical compounds that are foreign to the body
A
Xenobiotics
2
Q
Metabolism of Xenobiotics: Phase 2 Reaction
A
Conjugation reactions
Enzymes: Glucoronosyltransferases, sulfotransferases, glutathione S-transferases
3
Q
The monomer units or building blocks of nucleic acids
A
Nucleotides
4
Q
Nitrogen-containing heterocycles, cyclic compounds whose rings contain both carbon and other elements
A
Purines and Pyrimidines
5
Q
Sugar + Purine or Pyrimidine; the link is a ring nitrogen
A
Nucleoside
6
Q
Nucleosides with a phosphoryl group esterified to a hydroxyl group of the sugar
A
Nucleotides
7
Q
5’-phosphoryl group forms a phosphodiester bond with the 3’-OH of another nucleotide; Pgosphodiesterases catalyze the hydrolysis of phosphodiester bonds
A
Polynucleotides
8
Q
Purine ring is constructed by adding carbons and nitrogens to a preformed ribose-5-phosphate
A
Purine Synthesis
9
Q
Purine Synthesis: Sources of atoms
A
Aspartic acid Glycine Glutamine Carbon dioxide N10-formyltetrahydrofolate and N5, N10-methenyltetrahydrofolate
10
Q
In contrast, the pyrimidine ring is synthesized before being attached to ribose 5-phosphate
A
Pyrimidine Synthesis
11
Q
Pyrimidine Synthesis: Sources of atoms
A
Glutamine
Aspartic acid
Carbon dioxide
12
Q
What are the 2 compounds used in Purine Synthesis but not used in Pyrimidine Synthesis?
A
Glycine
N10-formyltetrahydrofolate and N5, N10-methenyltetrahydrofolate
13
Q
An activated pentose that participates in the synthesis of purines and pyrimidines, and in the salvage of purine bases
A
Synthesis of 5-phosphoribosyl-1-pyrophosphate (PRPP)
Substrates: ATP and ribose 5-phosphate
Enzyme: PRPP synthetase
14
Q
This is a committed step in purine nucleotide biosynthesis
Enzyme: glutamyl PRPP amidotransferase
A
Synthesis of 5’-phosphoribosylamine
15
Q
9 steps that lead to the synthesis of IMP; “Parent” purine nucleotide
A
Synthesis of inosine monophosphate
16
Q
Requires a two-step energy-requiring pathway; AMP synthesis requires GTP, while GMP synthesis requires ATP
A
Conversion of IMP to AMP and GMP
17
Q
Purines that result from the normal turnover of cellular nucleic acids or that are obtained from the diet and not degraded, can be reconverted into nucleoside triphosphates and used by the body
A
Salvage Pathways for Purines
18
Q
Salvage Pathways for Purines: Irreversible Enzymes
A
Adenine phosphoribosyltransferase (APRT) Hypoxanthine-guanine phosphoribosyltransferase (HGPRT)
19
Q
Steps in De Novo Pyrimidine Synthesis: Regulated and Rate limiting step
Enzyme: Carbamoyl phosphate synthetase II
Inhibited by UTP
Activated by ATP and PRPP
A
Synthesis of Carbamoyl phosphate
20
Q
Steps in De Novo Pyrimidine Synthesis: Dihydroorotate reductase is located inside the mitochondria; All the rest are cystosolic
A
Synthesis of Orotic Acid
21
Q
Steps in De Novo Pyrimidine Synthesis: The “parent” pyrimidine nucleotide is Orotidine monophosphate (OMP)
A
Formation of Pyrimidine nucleotide
22
Q
Steps in De Novo Pyrimidine Synthesis: Enzyme: CTP synthetase
A
Synthesis of UTP and CTP
23
Q
Steps in De Novo Pyrimidine Synthesis: Enzyme: Thymidylate synthase; N5N10-methyltetrahydrofolate is the source of the methyl group
A
Synthesis of dTMP from dUMP
24
Few pyrimidine bases are salvaged in human cells
Salvage Pathway for Pyrimidines
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Nucleoside diphosphates are synthesized from the corresponding nucleoside monophosphates using base-specific nucleoside monophosphate kinases
Conversion of nucleoside monophosphate to nucleoside diphosphates and triphosphates
26
Enzyme: Ribonucleotide reductase;
| It is multisubunit enzyme that is specific for the reduction of necleoside diphosphates to their deoxy forms
Synthesis of Deoxyribonucleosides
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Degradation of dietary nucleic acids occurs in the small intestines where a family of pancreatic enzymes hydrolyze the nucleotides to nucleosides and free bases
Purine Degradation
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The pyrimidine ring can be opened and degraded to highly soluble structures
Pyrimidine Degradation
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Sulfonamides are structural analogs of PABA that competitively inhibit bacterial synthesis of folic acid
PABA analogs
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Methotrexate and TMP inhibit the reduction of dihydrofolate to tetrahydrofolate, catalyzed by dihydrofolate reductase
Folic Acid analogs
31
Hyperuricemia with recurrent attacks of acute arthritis caused by deposition of uric acid crystals
Gouty Arthritis
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X-linked recessive deficiency in HGPRT that causes a rise in intracellular PRPP and hyperuricemia; triad of hyperuricemia, mental retardation, self-mutilation
Lesch-Nyhan Syndrome
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Purine overproduction and hyperuricemia occurs secondary to enhanced generation of PRPP precursor ribose 5-phosphate
Von Gierke's Disease
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Leads to severe combined immunodeficiency (both T and B lymphocytes affected)
Adenosine deaminase deficiency
35
Metabolically converted to 5-FdUMP which becomes permanently bound to the inactivated thymidylate synthase
5-Fluorouracil
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Low activities of orotidine phosphate decarboxylase and orotate phosphoribosyltransferase result in: Abnormal growth, megaloblastic anemia, excretion of large amounts of orotate in urine
Orotic Aciduria
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Deoxyribonucleic acid; A polymer composed of nucleotide building blocks
DNA
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5'-OH group attached to 3'-OH group; strands have directionality; bonds are cleaved hydrolytically by chemicals or hydrolyzed enzymatically by exonucleases or endonucleases
3'-5' Phosphodieters bonds
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Strands run in opposite directions
Antiparallel Strands
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Held together by hydrogen bonds and hydrophobic interactions
Complementary base pairing
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In any sample of dsDNA, the amount of adenine equals the amount of thymine, the amount of guanine equals the amount of cytosine
Chargaff's Rules
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Temperature at which one half of the helical structure is lost;
Under appropriate conditions, denaturation (annealing) may occur
Melting Temparature
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Most common; Right-handed helix with 10 residues per 360 turn of the helix
B-DNA
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Moderately dehydrated B form, also right-handed with about 11 base pairs per turn
A-DNA
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Left-handed helix that contains about 12 base pairs per turn, naturally in regions of alternating purines and pyrimidines
Z-DNA
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Five classes of small, positively charged proteins that form ionic bonds with negatively charged DNA
Histones
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Further packing of DNA due to hydrophobic interactions and in association with other non-histone proteins compacts it into _____
Chromatin
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Densely packed and transcriptionally inactive chromatin during interphase, observe by electron microscopy
Heterochromatin
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Transcriptionally active chromatin that stains less densely
Euchromatin
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Also called a nucleofilament; nucleosomes that are packed more tightly; Organized into loops that are anchored by a nuclear scaffold containing several proteins
Polynucleosome
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Prokaryotic DNA Synthesis: Group of proteins that recognize the origin of replication
Step 1: DNA A protein
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Prokaryotic DNA Synthesis: unwind the double helix ahead of the advancing replication fork
Step 2: Helicase
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Prokaryotic DNA Synthesis: Maintain the separation of the parental strands
Step 3: Single-stranded DNA-binding proteins
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Prokaryotic DNA Synthesis: Remove supercoils that interfere with the further unwinding of the double helix
Step 4: DNA topoisomerases
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DNA Toposiomerase: Type I
Swivelase (cleaves one strand)
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DNA Toposiomerase: Type II
Gyrase (cleaves both strands; target of quinolone antibiotics)
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Prokaryotic DNA Synthesis: Synthesize short stretches of RNA called primers, needed by DNA polymerase to begin DNA chain elongation
Step 5: Primase
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Prokaryotic DNA Synthesis: Catalyzes chain elongation, using 5'-deoxyribonucleoside triphosphates as substrates
Step 6: DNA Polymerase III
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Prokaryotic DNA Synthesis: Removes RNA primers using its 5'-3' exonuclease activity and fills in the resulting gaps
Step 7: DNA Polymerase I
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Prokaryotic DNA Synthesis: Seals the nicks between Okazaki fragments and catalyzes the final phospholipid ester linkage
Step 8: Ligase
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Stretches of highly repetitive DNA found at the ends of linear chromosomes; As cells divide and age, these sequences are shortened, contributing to cell death
Telomeres
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Make a DNA copy of their RNA, integrate that copy into host cells; lack of proof reading explains high mutation rate
Reverse transcriptase
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Mismatched strand, escaped proofreading
DNA Damage
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Identification of the mismatched strand
DNA Repair
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DNA Repair: Copying errors (single base or two to five base unpaired loops); Methyl-directed strand cutting, exonuclease digestion, and replacement
Mismatch Repair
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DNA Repair: Spontaneous, chemical, or radiation damage to a single base; Base removal by N-glycosylase, abasic sugar removal, replacement
Base Excision Repair
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DNA Repair: Spontaneous, chemical, or radiation damage to a DNA segment; Removal of an approximately 30-nucleotide oligomer and replacement
Nucleoside Excision Repair
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DNA Repair: Ionizing radiation, chemotherapy, oxidative free radicals; Synapsis, unwinding, alignment, ligation
Double-Strand Break Repair
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Polymers of nucleotides, but differ from DNA by containing: Ribose instead of deoxyribose, Uracil instead of thymine
RNA
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"Rampant" because it is the most common type of RNA; Associated with several proteins as a component of the ribosomes
Ribosomal RNA or rRNA
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"Tiny" because it is the smallest RNA; Adaptor molecule that carries a specific amino acid to the site of protein synthesis
Transfer RNA or tRNA
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"Massive"; Carries genetic information from the nuclear DNA to the cytosol, where it is used as the template for protein synthesis
Messenger RNA or mRNA
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A subset of RNAs significantly involved in mRNA processing and gene regulation
Small nuclear RNA or snRNA
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4-subunit enzyme that synthesizes RNA; Possesses 5'-3' polymerase activity
RNA polymerase
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Recognizes the nucleotide sequence (promoter region) at the beginning of the length of the DNA to be transcribed
Sigma factor
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Required for termination of transcription of some genes
Rho factor
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Prokaryotic DNA Transcription: RNA polymerase holoenzyme binds to the promoter region
Step 1: Initiation
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Prokaryotic DNA Transcription: RNA polymerase copying one strand of the DNA double helix, pairing Cs with Gs and As with Us
Step 2: Elongation
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Prokaryotic DNA Transcription: Maybe accomplished by RNA polymerase alone or may require ρ factor
Step 3: Termination
80
Stretch of 6 nucleotides (5'-TATAAT-3') centered about 8 to 10 nucleotides to the left of the transcription start site
Pribnow Box
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Second consensus nucleotide sequence (5'-TTGACA-3') about 35 bases to the left of the transcription start site
-35 Sequence
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Classes of RNA polymerase: For large rRNAs in the nucleolus
RNA Polymerase I
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Classes of RNA polymerase: For mRNAs
RNA Polymerase II
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Classes of RNA polymerase: For tRNAs and some other small rRNAs in the nucleoplasm
RNA Polymerase III
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TATA or Hogness box, CAAT box and GC box; Serve as binding sites for proteins called general transcription factors
Promoter Sequences
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DNA sequences that increase the rate of initiation of transcription by binding to specific transcription factors called activators
Enhancers
87
Linear copy of the transcriptional unit, the segment of DNA between specific initiation and termination sequences
Primary transcript
88
Synthesized from long precursor molecules called preribosomal RNAs
rRNAs
89
Also made from longer precursor molecules; these must have an intervening sequence removed and the 5' and 3' ends of the molecule are trimmed by ribonuclease
tRNAs
90
Regulation of gene expression in prokaryotes usually involves either initiation or termination of transcription
Genetic Regulation
91
A set of structural genes coding for a group of proteins required for a particular metabolic function along with the regulatory region that controls the expression of the structural genes
Operon
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Portion of the bacterial chromosome that controls the synthesis of the enzymes involved in lactose metabolism
Lactose Operon
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Encodes a β-galactosidase
Z gene
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Encodes a galactosidase permease, the transport protein required for the entry of lactose into the cell
Y gene
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Encodes a lac repressor protein that is constitutively expressed and located at a distant site in the DNA
i gene
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Encodes a thiogalactoside transacetylase enzyme, whose function is unknown
A gene
97
Proteins translated on Ribosomes associated with RER
Secreted proteins
Proteins inserted into the cell membrane
Lysosomal enzymes
98
Proteins translated on free cytoplasmic ribosomes
Cytoplasmic proteins
| Mitochondrial proteins
99
Consists of three bases (triplet)
Codon
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Total number of codons
64 codons
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Total codons that code for amino acids
61 codons
102
Stop codons
Nonsense codons (UAA, UGA, UAG)
103
Start codon
Initiation codon (AUG)
104
A specific codon always codes from the same amino acid
Specific Genetic Code
105
It has been conserved from very early stages of evolution with only slight differences in the manner in which the code translated
Universal Genetic Code
106
A given amino acid may have more than one triplet coding for it
Redundant Genetic Code
107
Code is read from a fixed starting point as a continuous sequence of bases, taken three at a time
Commaless Genetic Code
108
Accurate base pairing is required only in the first 2 nucleotide positions of an mRNA codon, so codon differing in the 3rd wobble position may code for the same tRNA/amino acid
tRNA wobble
109
Binds an incoming aminoacyl-tRNA
A site codon
110
Occupied by peptidyl-tRNA
P site codon
111
Occupied by the empty tRNA as it is about to exit the ribosome
E site codon
112
Amino-acetyl-tRNA synthetase (1perAA) uses an ATP scrutinizes an amino acid before and after it binds to tRNA
Charging
113
DNA Translation: Activated by GTP hydrolysis, initiation factors (eIFs) help assemble the 40s ribosomal subunit with the initiator tRNA and are released when the mRNA and the ribosomal unit assemble with the complex
Step 1: Initiation
114
DNA Translation: Aminoacyl-tRNA binds to A site; Elongation factors direct the binding of the appropriate tRNA to the codon in the empty A site
Step 2: Elongation
115
DNA Translation: Releasing factors are proteins that hydrolyze the peptidyl-tRNA bond when a stop codon occupies the A site
Step 3: Termination
116
Energy Requirements of Translation
1) tRNA aminoacylation (ATP➡️AMP)
2) Loading tRNA onto ribosome (GTP➡️GDP)
3) Translocation (GTP➡️GDP)
117
Post-translational Modification
1) Trimming excess amino acids
2) Phosphorylation
3) Glycosylation
4) Hydroxylation
5) Destruction by Ubiquitin
118
Any permanent heritable change in the DNA base sequence of an organism; Has the potential to change the base sequence of mRNA and the amino acid sequence of proteins
Mutation
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Point Mutation: Purine-Pyrimidine to Purine-Pyrimidine
Transition
120
Point mutation: Purine-Pyrimidine to Pyrimidine-Purine
Transversion
121
New codon specifies same amino acid, often base change in 3rd position of codon
Silent Mutation
122
New codon specifies a different amino acid
Missense Mutation
123
New codon is a stop codon; Shorter than normal protein, usually nonfunctional
Nonsense Mutation
124
Deletion or addition of a base; Protein usually nonfunctional, often shorter than normal
Frame shift Mutation
125
Unequal crossover in meiosis; Loss of function, protein shorter than normal or entirely missing
Large segment deletion Mutation
126
A splice site is lost through mutation
Splice donor or acceptor Mutation
127
Expansions in coding regions cause protein product to be longer than normal and unstable
Triple repeat expansion Mutation
128
Used to deduce original sequence of DNA; Dideoxynucleotides halt DNA polymerization at each base, generating sequences of various lengths that encompass the entire sequence
Sanger DNA Sequencing
129
Molecular biology lab procedure that is used to synthesize many copies of a desired fragment of DNA
Polymerase Chain Reaction
130
A DNA sample is electrophoresed on a gel and then transferred to a filter
Southern Blot
131
Similar technique but involves radioactive DNA probe binding to sample RNA
Northern Blot
132
Sample protein is separated via gel electrophoresis and transferred to a filter
Western Blot
133
Thousands of nucleic acid sequences are arranged in grids on glass or silicon
Microarrays
134
Enzyme-linked immunosorbent assay; A rapid immunologic technique testing for antigen-antibody reactivity
ELISA
135
Flourescence in situ hybridization; Flourescence probe binds to specific gene site of interest
FISH
136
Inherited difference in the pattern of restriction; Important in understanding various single-gene and multigenic diseases
Restriction Fragment Length Polymorphism
137
The production of recombinant DNA molecule that is self-perpetuating
Cloning
138
Treatment option for diseases caused by deficiency of a gene product
Gene Treatment
