Exam 2 Study Guide Flashcards
1
Q
What are genetic markers?
A
Particular sequences of DNA that correlate with disease
2
Q
What are Genome Wide Association Studies (GWAS)?
A
Correlative studies of DNA sequence variants to see if they are associated with a human disease
3
Q
What are anonymous markers?
A
Sequences of DNA not associated with disease or trait (no phenotypic affect)
4
Q
What are some traits of anonymous markers?
A
Highly variable (polymorphic), multiple alleles, high degree of heterozygosity
5
Q
What is single nucleotide polymorphism (SNP)?
A
One base difference between individuals; 7 million+
6
Q
What are the two types of SNPs?
A
Coding and noncoding
7
Q
What are the two types of coding SNPs?
A
Synonymous and non-synonymous
8
Q
What does synonymous coding do?
A
Doesn’t change protein the gene codes for
9
Q
What does non-synonymous coding do?
A
Changes the protein the gene codes for
10
Q
What are Variable Nucleotide Tandem Repeats (VNTRs)?
A
Short repeated DNA sequences that vary in length (10-100 bp) and number of repeats (3-50) among individuals; thousands of VNTR loci in human genome
11
Q
What demonstrates VNTR length?
A
DNA fingerprint, amplified in polymerase chain reaction analyzed through gel electrophoresis
12
Q
What is identity matching?
A
Matching a suspect’s DNA with DNA at a crime scene. To match two samples , they must show the same allele pattern. (CODIS uses 15 VNTR loci)
13
Q
What is inheritance matching?
A
VNTR alleles must follow rules of inheritance. In matching an individual with his parents or children, a person must have a VNTR allele that matches one from each parent
14
Q
What is gene expression?
A
How genotype is converted into phenotype
15
Q
What is the Central Dogma of Molecular Biology (CDMB)?
A
Unifying concept of molecular biology; describes information flow within cells
16
Q
According to the CDMB, what is the information flow within cells?
A
DNA stores info and is replicated, RNA contains information in DNA, RNA is used to direct synthesis of proteins
17
Q
What is the Updated Central Dogma?
A
Adds additional step that DNA can be made from RNA through reverse transcription (e.g. retroviruses like HIV have reverse transcriptase that can be used to make complementary DNA (cDNA) from RNA)
18
Q
What did Beadle and Tatum do?
A
Studied synthesis of arginine in Neurospora (bread mold), exposed bread mold to x-rays which would cause mutations
19
Q
What are the putative precursors of arginine?
A
Ornithine and citruline
20
Q
What is the conclusion about each gene Beadle and Tatum mutated?
A
Each mutated gene encoded a single enzyme in the Arg synthesis pathway
21
Q
Why is “one gene-one polypeptide” more correct than Beadle and Tatum’s original “one gene-one enzyme”?
A
An enzyme may be made up of multiple polypeptides; also, a polypeptide may not be an enzyme at all (a structural protein)
22
Q
What may happen if alternative splicing occurs?
A
One gene may code for multiple proteins
23
Q
How does a DNA sequence specify amino acids in a protein?
A
The genetic code
24
Q
What was a milestone of the 20th century?
A
Cracking the code by identifying three base codons
25
What combination of scientific specialties identify codons and the role of RNAs in protein synthesis?
Genetics, biochemistry, and organic chemistry
26
How many naturally occuring amino acids are there?
20
27
How many DNA bases are there?
4
28
How many amino acids can 1 base code for?
4
29
How many amino acids can 2 bases code for?
16
30
How many amino acids can 3 bases code for?
64
31
Who first proposed the DNA base-amino acid logic and who later verified it experimentally?
Gamow; Nirenberg
32
What was the first-made synthetic RNA polymer?
PolyU
33
When translating RNA polymer with cell extract, what is made?
Proteins
34
What protein does PolyU make?
Phe-Phe-Phe-Phe (PolyPhe)
35
What is the 3-base equivalent of PolyPhe?
UUU
36
What is the 3-base equivalent of lysine?
AAA
37
What is the 3-base equivalent of proline?
CCC
38
What are copolymers?
Polymers with more than one base
39
After translating copolymers with cell extract and varying the ratio of bases, what is induced?
Frameshift rotations
40
The nature of code is universal. What does that mean?
Virtually the same in all organisms on the planet (rare exceptions exist in some mitochondria, protozoans and mycoplasma)
41
What is the equivalence ratio of bases to codons to amino acids?
3 : 1 : 1
42
How is coding redundant?
61 codons encode amino acids, more than one codon for some amino acids, redundancy usually in 3rd position
43
Code has how many start codons?
1 (AUG, Met)
44
Code has how many stop codons?
3 (UGA, UAG, UAA)
45
Is there any punctuation other than start/stop?
No
46
At its most basic, what is RNA?
Single stranded and only synthesized 5' to 3'
47
What is messenger RNA (mRNA)?
Contain genetic information in the form of RNA and is used to direct the synthesis of a protein
48
What is ribosomal RNA (rRNA)?
Combine with ribosomal proteins to form the ribosome; not translated
49
What is transfer RNA (tRNA)?
Carry amino acids to the ribosome for incorporation into a polypeptide
50
What is micro RNA (miRNA)?
Very small RNAs that interact with mRNA to 'silence' them by preventing their translation into proteins
51
What is small nuclear RNA (snRNA)?
RNAs of **~150** nucleotides in length, involved in the **regulation of mRNA splicing**, and the regulation of **gene transcription**
52
Essentially, what is transcription?
How all RNAs are made
53
What enzyme carries out transcription?
RNA Polymerase
54
In transcription, the RNA is complementary to what?
The DNA ‘Template’ or antisense strand
55
In transcription, the RNA sequence is essentially what?
A copy of the ‘Coding’ or sense strand
56
Prokaryotic transcription and translation happen at the same time and place in the cell; what is this called?
Spatial and temporal coupling
57
When is a prokaryotictranscript (mRNA) translated?
As soon as it is made
58
In prokaryotic RNA transcript, are any additional modifications made?
No
59
Where does prokaryotic gene expression occur?
It all occurs in the cytoplasm (no nucleus)
60
In prokaryotic gene expression, what does single RNA Polymerase do?
Coordinate regulation of genes with similar function (Gene clusters called operons)
61
What is a promotor sequence?
Typically upstream (5’ end) of gene, where RNA polymerase binds
62
What is the TATA Box?
A conserved sequence in the promoter of archaea and eukaryotes (TATAAT in eubacteria)
63
What tells RNA Polymerase to stop?
Termination sequence
64
Are the promotor and termination regions transcribed?
No
65
What are the three stages of transcription?
Initiation, elongation, and termination
66
What is prokaryotic RNA Polymerase made up of?
Subunits that assemble for initiation
67
What do core enzymes do?
Synthesize RNA; 2 alpha and 2 beta
68
What do sigma factors do?
Recognize promotor region and disrupts hydrogen bonds
Binds the core enzyme to the promoter region, helps in the initial unwinding of the DNA so transcription can begin
69
What is RNA Polymerase?
A large multisubunit enzyme
70
What is a promotor?
Where RNA Polymerase attaches to the gene
71
What are holoenzymes?
Necessary for the accurate initiation of transcription; core + sigma factor; recognizes promotor
72
In prokaryotes, are additional proteins required such as transcription factors in eukaryotes?
No
73
Which was does prokaryotic transcription run?
Synthesized 5' to 3'
74
What is required in prokaryotic transcription?
DNA template and RNA monomers (ribonucleoside tri-phosphate (rNTP’s) A, U, G, and C)
75
What does core polymerase do?
Carries out transcription elongation
76
What happens once transcription begins?
Sigma factor dissociates from the core enzyme
Core enzyme continues transcription until termination
Sigma factor can go associate with other core enzymes
77
What happens during prokaryotic initiation?
Requires a specific site on DNA
Promotors are recognized by RNA holoenzyme
78
What is prokaryotic elongation?
Similar to DNA synthesis except:
Only one strand is being transcribed
Only a small section of DNA is unwound at any one time (transcription bubble)
79
What is prokaryotic termination?
Requires specific sequences on DNA
Terminator is recognized by core enzyme
Core enzyme releases from the DNA and RNA transcript
80
Many prokaryotic mRNA transcripts in bacteria are polycistronic, meaning what?
More than one gene is included in one mRNA transcript
81
What do operons usually contain?
Genes involved in similar biochemical pathways
82
What are lac operons?
Clusters of genes involved in the transport and metabolism of lactose into glucose and galactose for energy
Three proteins are made from one mRNA transcript
83
When do transcription and translation occur in prokaryotes?
Simultaneously
84
In eukaryotes, are transcription and translation coupled?
No
85
Where does eukaryotic transcription take place?
Nucleus
86
Where does eukaryotic translation take place?
Cytoplasm
87
How many RNA Polymerases are involved in eukaryotic gene expression?
Three
88
Eukaryotic transcript is processed (additionally modified) to make what?
A mature mRNA
5' Methyl Cap
3' Poly A Tail
89
What is spliced to make a mature mRNA?
RNA primary transcript
90
What does RNA Polymerase I do?
Transcribes rRNA
91
What does RNA Polymerase II do?
Transcribes mRNA (and snRNA, miRNA)
92
What does RNA Polymerase III do?
Transcribes tRNA, rRNA
93
What are the initial and final products of mRNA transcription?
Initial product transcribed by Pol II: primary transcript called (heteronuclear RNA = hnRNA) or pre-mRNA
Final product: mature mRNA, after processing
94
Why is eukaryotic initiation more complex than in bacteria?
Pol II has no sigma factor
Instead other proteins are involved in getting Pol II to bind the promoter region
95
How does eukaryotic elongation compare to prokaryotic elongation?
Similar; 5' methyl cap is also added
96
How is eukaryotic termination different from prokaryotic termination?
RNA modification
A Poly A tail will be added to the 3’ end of the newly transcribed mRNA
97
Eukaryotic initiation requires transcription factors; what are the general ones?
Necessary for basal level of transcription; form initiation complex and attract RNA pol II to the promoter (these are common in all cell types).
98
Eukaryotic initiation requires transcription factors; what are the specific ones?
Specific to certain cell types or produced in cells only under certain conditions to raise the transcription level of particular genes
99
In eukaryotic initiation, what are promotor regions?
Binding site of general factors
100
In eukaryotic initiation, what are enhancer regions?
Binding site of specific factors; may act over long distances so may be far away from promoter
Human genome contains 100,000s
101
In eukaryotes, what is the initiation complex?
Consists of transcription factors plus RNA Polymerase II
102
What can silencer sequences do in eukaryotes?
Decrease transcription
103
What happens during eukaryotic elongation/termination?
mRNA is capped at 5’ end with methyl-G-Cap with aid of methyl transferase while elongation is in progress.
104
How is eukaryotic elongation similar to that of prokaryotes?
5' to 3' (about 20 bases per second)
Occurs in transcription bubble
105
How does eukaryotic termination differ from that of prokaryotes?
Have terminator sites but end of message is not end of transcript
mRNA is cleaved at the 3’ end after transcription
~200 A’s added by PolyA Polymerase to produce 3’ poly A tail
3’ end of mRNA not created by Polymerase II
106
Why is there no no 5’ methyl cap or Poly A tail in prokaryotes?
RNA splicing
107
In RNA splicing, what does an exonic mRNA sequence do?
Encodes a protein
108
In RNA splicing, what does an intronic mRNA sequence do?
Noncoding
109
RNA transcript starts off as containing what?
Both introns and exons, heteronuclear RNA (hnRNA)
110
What does the 3' Poly-A tail do?
Prevents mRNA from being degraded
111
What does the 5' mG Cap do?
Prevents degradation and is important for positioning of the mRNA on the ribosome
112
What is splicing?
Removal of introns and ligation of exons
Must be exact or mRNA will not be properly translated
113
What is the splicing enzyme?
Spliceosome
114
What is the spliceosome?
Enzyme made up of snRNA and snRNP 'snurps'
115
How many snRNAs are in the spliceosome complex?
6 types (uridine rich): U1, U2, U3, U4, U5, and U6
116
What are snRNPs (small nuclear ribonucleoproteins)?
Proteins complexed with uridines (an RNA base similar to uracil)
117
What happens during splicing?
1. snRNAs bind to specific RNA sequences at the 5' and 3' ends of the intron (Branch point A)(adenine nucleotide)
2. snRNPs associate with other factors to form the spliceosome
3. Intron is cleaved out and attached to itself forming a lariat structure
4. Exons are joined (spliced together)
118
What is alternative splicing?
Exons can be joined together in different combinations to generate multiple mRNA and multiple proteins
Can be cell type or sex specific or developmentally specific (i.e. time specific)
119
What is an example of alternative splicing in humans?
Tyrosinase in melanocytes (5 combinations); dystrophin protein in muscle (79 exons, 18 combinations)
120
How many mRNAs can one gene have?
Multiple that code for multiple proteins
121
Does alternative splicing alter gene products?
Yes
122
What percentage of human genes are alternatively spliced?
40%
(25,000 genes can produce 80,000 different mRNAs)
123
What can Misregulated or aberrant RNA splicing lead to?
Disease (i.e. autism, cancer)
124
What are cancer-associated splicing changes (CASCs)?
In proteins, they are known to be involved in oncogenesis, could represent an important new mechanism in how cells become cancerous
125
What is the most energy-expensive step in gene expression?
Protein synthesis/translation
126
Protein synthesis/translation uses information in mRNA to produce what?
A polypeptide
127
What are the necessary components of protein synthesis/translation?
'Charged' tRNA (tRNA carrying an amino acid)
Ribosomal platform (mRNA)
Ribosomal complex
128
What is a "charging reaction"?
How amino acids become covalently bound to tRNAs
129
What is aminoacyl-tRNA synthetase?
The enzyme that catalyzes the charging reaction
There are 20 aminoacyl-tRNA synthetases, one for each of the 20 amino acids
Reaction requires energy (ATP)
130
How do ribosomes play a role in gene expression?
Factory floor for translation
Huge macromolecular structure composed of rRNA and proteins
Organized into large and small subunits
Minor structural, but not functional, differences between prokaryotic and eukaryotic ribosomes
131
When do large and small ribosomal subunits come together?
AFTER mRNA has been positioned on the small subunit
132
What was the original view of ribosome function?
rRNA was "structural" and the proteins "active"
133
What is the new view of ribosome function?
Ribosomes contain enzymatic RNA (ribozymes). Ribozymes catalyze the reactions that form the peptide bonds and release the finished peptide
134
What are the functions of the large and small ribosome subunits?
Positioning of the mRNA (small subunit)
Binding 2 charged tRNAs (both subunits)
Peptidyl transferase activity (large subunit)
Recognition of the stop codon and peptide release (large subunit + a protein release factor)
135
What are the phases of translation?
Initiation: assemble ribosome/mRNA/charged-tRNAs
Elongation: form successive peptide bonds and add amino acids to growing polypeptide chain
Termination: cleave peptide from last tRNA, release protein and mRNA, disassemble the ribosome
136
What happens during prokaryotic initiation (translation)?
Small ribosomal subunit + other factors bind the mRNA at the 5' ribosomal binding sequence
The initiator tRNA binds to the start codon (AUG)
The large ribosomal subunit joins and initiation is complete
137
What happens during eukaryotic intitiation (translation)?
The small ribosomal subunit + initiator Met tRNA and other factors bind to the 5' cap
The complex scans the mRNA until it finds the start codon (AUG)
The large ribosomal subunit joins the complex and initiation is complete
138
In genetic code, how many possible codon sequences are there?
64
139
Which sequences are stop codons?
UAA, UAG, UGA
140
What is the Codon/Anticodon Conundrum in Translation?
In the genetic code, there are 64 possible codon sequences (UAA, UAG, UGA) are stop codons
If there were a different tRNA to pair up with each possible codon combination, there would be 61 tRNAs
However msot organisms only have 45 different tRNAs
So, there are 16 codons that specify an amino acid but have no tRNA to match them
141
What is Wobble Base Pairing?
Base pairing in the 3rd position of a codon is weaker and more flexible than base pairing in the first 2 positions; allows 1 tRNA to read (or pair with) more than 1 codon
142
What joins AAs?
Covalent bonds
143
Where does peptide bond formation occur?
On the ribosome
144
What happens in elongation (translation)?
* The first charged tRNA binds to the P site
1. A new charged tRNA binds to the A site
2. Formation of the peptide bond
* Growing aa chain now is transferred from the tRNA in the P site to the tRNA in the A site
* tRNA in P site now has no aa (uncharged)
3. The ribosome moves relative to mRNA. This is called TRANSLOCATION
* Shifts the uncharged tRNA in P site to the E site (ejected)
* A new charged tRNA binds to the codon in the A site
145
What happens as release factors are recruited by a stop codon in the A site?
1. break the covalent bond between the polypeptide and the acceptor stem of the tRNA in the P site, and
2. cause the ribosomal subunits to dissociate
146
After release factors are recruited by a stop codon in the A site, now what happens to the protein?
The protein will be transported to its proper location in the cell, or the protein will be exported out of the cell
Locational markers are present in the protein itself in parts of the protein called signal sequences (SS)
SS: are 16-30 amino acids long and act as an address or zip code for the protein
147
What happens during the post-translational processing of proteins?
1. Proteins may be cleaved after synthesis (proteolysis)
1. Example: zymogens: enzymes that are not active until they are cleaved
2. Glycosylation: the addition of sugars to a protein
1. Many membrane-bound organelles are glycoproteins
3. Phosphorylation: addition of PO4 group(s) to a protein
1. The activity of many proteins are controlled by phosphorylation (cell cycle)
1. Phosphotases and kisases: enzymes that control phosphorylation
2. Phosphorylation can activate or deactivate the activity of a protein
4. Ubiquitination: addition of ubiquitin (itself a small protein)
1. Targets protein for destruction in the proteosome
1. Addition of 4 ubiquitins is required for destruction
148
What is the main rule of protein structure?
To be functional, proteins must be properly folded
149
What characteristics denote primary structure?
The sequence of amino acids, which is determined by the gene that codes for the protein
All higher levels of structure are dependent on primary structure
Peptide bonds present
150
What characteristics denote secondary structure?
Arises through hydrogen bonding between the amino hydrogen and carboxyl oxygen atoms in the peptide backbone
Does not involve R group interactions
Alpha-helix
Beta-pleated sheets: consists of two or more hydrogen bonded beta-strands (Hydrogen bonds, although weak, provide structure stability due to the large number of them present)
151
What are motifs?
The next level of secondary structure
Different combinations of beta-pleated sheets and/or alpha-helices form motifs
A beta-barrel is a large beta-sheet that twists and coils to form a closed tube that resembles a barrel
Often found in proteins that form pores in plasma membranes
152
What characteristics denote tertiary structure?
3D shape of the entire protein; includes the secondary structure and arises through interactions between the R groups of the amino acids
153
What R-group interactions exist in tertiary structures?
Electrostatic (H-bonding and ionic): attraction of positive and negatively charged R groups
Disulfide bridges: cysteine have sulfhydryl (SH) groups, which react to form covalent bond: disulfide (S-S)
Van der Waals Interaction: attraction of nonpolar groups for each other (a weak attractive force between the two nonpolar atoms due to small fleeting changes in atomic charge
Hydrophobic exclusion interactions: hydrophobic side chains will prefer to be in the interior of the protein to avoid contact with the aqueous environment
154
What are domains?
Functional units of the protein within a tertiary structure
If amino acids are the letters of a protein, secondary structures and motifs are the words and phrases of a protein and domains are the chapters of a protein
Most have multiple domains
If a protein is only one polypeptide, this is the highest level of structure
155
What are some examples of protein domains?
DNA binding domain (DBD): any protein that directly binds to DNA (transcription factor) will need a DNA binding domain
Any protein that activates transcription of a gene will need Transcriptional Activation Domain (TAD) to recruit RNA Polymerase
Scientists can deduce the function of a protein by what domains it has
156
What characteristics denote quaternary structure?
Relevant for proteins made up of multiple polypeptides (highest level of structure)
Example: hemoglobin protein in RBC's; Consists of two alpha and two beta chains
4 polypeptides=tetramer
157
What is denaturation?
Occurs in response to changes in temperature, pH, and/or ionic concentrations
All of these alter chemical interactions and change protein shape
158
What are chaperone proteins?
Enzymes that help proteins fold and/or refold
Chaperone proteins provide an optimal environment for the protein to fold in
Once thought that all newly-made proteins folded spontaneously, now know that chaperones assist in folding and/or refolding
159
What can misfolded proteins cause?
Disease, as proper folding is crucial to cellular function
160
What is cystic fibrosis?
An inherited disease in which abnormally thick mucus blocks airways causing difficulty breathing
A mutation in the CF transmembrane conductance regulator (CFTR) gene.
This mutation blocks the binding of CFTR protein with chaperone protein (causes CFTR misfolding)
161
How is Alzheimer's Disease related to misfolding?
Misfolded beta-amyloid proteins clump together to form plaques that collect between neurons and disrupt communications between neurons and cause cell death
Misfolded Tau proteins clump together to form tangles that collect inside the neuron and cause cell death
162
What are therapeutic strategies for misfolded proteins?
It’s known that Tau proteins are hyperphosphorylated in Alzheimer's
Inhibit tau protein kinases
Activate tau phosphatases
Promote the clearance of the abnormally hyperphosphorylated tau by targeting it for destruction using the ubiquitin proteasome system
163
Protein misfolding is believed to be the primary cause of:
Parkinson's disease
Huntington's disease
Creutzfeldt-Jakob disease
Many other degenerative and neurodegenerative disorders
164
What are ligands?
The signaling molecule sent out by cells that are talking
165
What cells receive the ligand with a receptor?
Cells that are listening
166
What does the ligand/receptor interaction do?
Conveys information across the membrane into the cell
167
What is autocrine signaling?
Cell signaling to itself
168
What are examples of autocrine signaling?
Immune cells: respond to wounds and infections by producing ligands that stimulate their own activation (amplifies the immune response)
Cancer cells: produce ligands that stimulate their own growth and mobility (contributes to tumor growth and metastasis)
169
What is direct cell-cell contact?
Communicate via gap junctions or surface receptors
170
What are examples of direct cell-cell contact?
Cell-cell interactions play a critical role during embryonic development, wound healing and the maintenance/repair of organs, muscles and other tissues of the body
171
What is paracrine signaling?
Cell signaling to nearby cells
172
What are examples of paracrine signaling?
Eicosanoids: signaling molecules secreted by cells that stimulate a variety of responses in their target cells, including the inflammation at sites of injury and smooth-muscle contractions
173
What is endocrine signaling?
Systemic signaling via the circulatory system
174
What are examples of endocrine signaling?
Hormones: produced by the gonads of males and females; stimulate development and maintenance of the reproductive system and secondary sexual characteristics
175
What is synaptic signaling?
Similar to paracrine, but there is a synapse between the signaling nerve cell, and the cell receiving the signal
176
What are examples of synaptic signaling?
Neurotransmitters: signaling molecules sent between a neuron and another neuron or a muscle that is controlled by neural activity
177
Can ligands be hydrophobic or hydrophilic?
They can be both!
178
Are cytoplasmic receptors intercellular or intracellular?
Intracellular
179
What do hydrophobic ligands do?
Hydrophobic ligands such as hormones diffuse across the plasma membrane and bind to intracellular receptors
Intracellular receptors then transmit the signal to the nucleus causing a cellular response
180
What can cytoplasmic hormone receptors double as?
Transcription factors
181
What happens to receptors with no hormone?
They become inactive transcription factors
182
How do hormones interact with their receptors?
Hormones bind to hormone receptors in the cytoplasm
Activated hormone receptor complex moves into the nucleus
Binds directly to enhancers, changes patterns of gene expression
183
What happens with membrane receptors?
Signals cannot pass plasma membrane
Hydrophilic ligands bind to transmembrane receptors
Ligand-bound receptor transmit the sigmal across the membrane causing a cellular response
184
What are ion channel-linked receptors that double as ion channels?
Found in nerve synpases; ligand binds and then ligand bonding opens an ion channel across the membrane
Allows ions such as Na+, K+, and Ca2+ to pass through the membrane in response to the binding of ligands
185
What are enzymatic (catalytic) receptors?
Binding of an extracellular ligand causes enzymatic activity on the intracellular side of the receptor
Many growth factor receptors are catalytic receptors
Enzymatic receptors are usually kinases (enzymes that phosphorylate other proteins)
Example: Receptor Tyrosine Kinase (RTK): adds PO4 to amino acid tyrosine residues in proteins; can autophosphorylate (add PO4 to itself) and to other proteins
186
What are kinase cascades?
When multiple kinases activate eachother in a particular order and ultimately alter the expression of genes
Ultimately, leads to the activation of transcription factors in the nucleus that alter gene expression
187
G Protein-Coupled Receptors (GPCRs)?
Receprots that interact with a G protein
G proteins bind GTP and hydrolyze it to GDP
The G protein is active when bound to GTP, inactive after it hydrolyzes the GTP to GDP
When bound to a ligand, GPCRs activate G proteins by helping them exchange GDP for a new GTP
Important in many signaling pathways; effector proteins produce second messenger molecules that mediate the cellular responses
188
What are 2nd messengers?
Ligand (1st messenger) interacts with GPCRs, leads to the activation of an effector molecule that produces a 2nd messenger
Short-lived intracellular signaling molecules
Elevated concentration of second messenger leads to rapid alteration in the activity of one or more cellula enzymes
Removal or degradation of second messenger terminate the cellular response
189
What are common 2nd messengers?
Inositol triphosphate (IP3): binds channel-linked receptor in the ER; causes release of intracellular ions and important for muscle function
cAMP made from ATP: involved in the activation of protein kinases. In addition, cAMP binds to and regulates the function of ion channels
190
What are agonists?
Pharmaceuticals that mimic action of ligand (activate receptor)
191
What are antagonists?
Pharmaceuticals that bind to but do not activate a receptor
192
Which drugs are commonly abused?
Drugs that activate the opioid receptor (GPCR)
193
What is Naloxone/Narcan?
Opiate receptor antagonist
Outcompetes agonists from binding to the opioid receptor
No agonistic activity (does not activate receptor)
Administered intravenously, intramuscularly blocks the effects of drugs such as heroine
194
What are epigenetic modifications?
Change gene expression without changing the DNA sequence; may be heritable; can change how strongly DNA and histones bind together
195
How do classic epigenetic modifications work?
By changing chromatin structure
196
What is chromatin?
DNA associated with histone proteins
197
What is a nucleosome?
146 bp of DNA wrapped around 8 histone proteins
198
What are the two types of chromatin in the cell?
Euchromatin and heterochromatin
199
What is euchromatin?
DNA and histones are *loosely* associated and DNA is available to transcription factors; can be expressed
200
What is heterochromatin?
DNA and histones are *tightly* associated and DNA is not accessible to transcription factors; cannot be expressed
201
What is chromatin remodeling?
Changing chromatin state between euchromatin and heterochromatin
202
What is the makeup of histone proteins?
Have amino terminal tails that extend out from the nucleosome core
203
What is histone acetylation?
Changes the positively charged lysine residues to negatively charged lysine residues
This change in histone charge reduces how tightly DNA binds to the histones; provides a more euchromatin structure for transcription factors
Involves the attachment of acetyl groups to lysine residues in the N-terminal tails of histones
204
What two types of enzymes control histone association
HATs and HDACs
205
What are Histone Acetyl Transferases (HATs)?
Carry out histone acetylation
206
What is hyperacetylation?
(histones more - charged)=relaxed chromatin, gene transcription is active
207
What are Histone Deacetylases (HDACs)?
Carry out histone deacetylation
208
What is hypoacetylation?
(histones more + charged)=closed chromatin, gene transcription is inhibited
209
What is DNA Methylation?
Methyl group is added to cytosine in DNA to form 5-methylcytosine
210
In DNA Methylation, what does the methyl group do?
Interferes with transcription factor binding to DNA (inhibits gene transcription)
211
What carries out cytosine methylation?
DNA Methyl Transferases (DNMTs)
212
What carries out cytosine demethylation?
DNA Demethylases
213
Where does DNA methylation occur?
Cytosines that are followed by a guanine (5' CG 3')
214
What are CpG islands?
CG-rich regions of DNA sequence within genes; C phosphodiester bonded to G
215
Where are CpG islands located?
Around the promoter and enhancer regions of genes
216
Different cell types have different methylation patterns which contribute to what?
The differences in gene expression in different cell types
217
What combines to remodel chromatin and affect gene transcription
Histone acetylation/deacetylation and DNA methylation/demethylation
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What increases secretion of dopamine in the brain area affecting wants and desires and increases drug-seeking behavior?
Drug-altered methylation
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What is genomic imprinting?
Specific example of gene methylation that is inherited by the offspring
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Genes that are paternally imprinted are only expressed on which chromosome?
Maternal chromosomes
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Genes that are maternally imprinted are expressed on which chromosome?
Paternal chromosomes
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What is parental conflict theory?
Genes that promote growth: paternally-expressed
Mutants show growth retardation
Genes that supress growth: maternally-expressed
Mutants have enhanced growth
Some imprinted genes affect the behavior of offspring
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What are other imprinting effects?
Early-life stresses can imprint the stress response of an organism into the offspring; results in increased reactivity of the hypothalamus-pituitary-adrenal axis (HPA axis)
Prenatal and early-life stress can cause offspring to suffer from chronic stress, anxiety, and depression through altered imprinting of genes critical to controlling the stress response
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What are the generational effects of early prenatal care?
Rats raised by attentive mothers were, as adults, able to deal with stress better than rats raised by negligent mothers
Levels of a receptor that regulates the reaction to stress hormones (glucocorticoids), were different in these two groups
A mother rat's level of maternal care leads to altered methylation patterns in the brains of rat pups
Methylation changes lead to the gene for the glucocorticoid receptor more accessible to transcription factos (excess expression)
