Exam 3 Flashcards
1
Q
Four elements of cell communication
A
Signaling cell
Signaling molecule
Responding cell
Receptor
2
Q
Steps in cell signaling
A
Receptor activation - ligand binds and activates a receptor
Signal transduction - signal is transmitted and amplified
Response - cells change protein activity
Termination - the system is reset
3
Q
What does high ligand concentration/binding affinity mean?
A
the response stronger and longer-lasting
4
Q
Ligands
A
Signaling SMALL molecule
Activate receptors
Ligand are released from receptors spontaneously and when they are, the receptor becomes inactive and does’t activate downstream proteins
5
Q
High/low affinity
A
High - ligands that bind for a long time
Low - ligands that rapidly disassociate
6
Q
Signal transduction
A
The receptor transmits a message to the cell through the cytoplasm
7
Q
High concentrations of signal transduction proteins mean what?
A
stronger and longer responses
8
Q
Response
A
Cell responds in many ways. It can:
Activate enzymes, turn genes, signal other cells, and cause the cell to divide or change shape
9
Q
Termination
A
Usually involves the ligand dissociating from the receptor and resetting the proteins in the signal transduction pathway
10
Q
What does strong termination response mean?
A
The effect of a ligand is short and weak
11
Q
Endocrine signaling
A
long-distance through blood
12
Q
Contact dependent signaling
A
One cell to another
A transmembrane ligand on one cell activates a transmembrane receptor on an adjacent cell
13
Q
Paracrine signaling
A
short-distance through a couple of cells
14
Q
Autocrine signaling
A
one cell to itself
the releasing cell has both the ligand and receptor
15
Q
Sonic Hedgehog (Shh) signaling pathway
A
In the spinal corn, gradients of Shh and other proteins determine neuronal identity
crucial developmental pathway involved in embryonic development, tissue homeostasis, and stem cell regulation
16
Q
Ligand binding does what?
A
changes the shape or conformation of the receptor (tertiary structure)
17
Q
What are the three main molecular switches
A
Ligand binding
Phosphorylation
GTP binding and hydrolysis
18
Q
Ligand binding
A
not a covalent linkage
Protein binds a small molecule and changes the shape and function of the protein
19
Q
allosteric effect
A
change of overall shape and function of a protein because of ligand binding
20
Q
Phosphorylation by kinases
A
the covalent addition of a phosphate group to an amino acid
Phosphates dramatically change proteins shape and activity due to its size and negative charge
turns on and off
21
Q
Dephosphorylation by phosphates
A
remove phosphate group
turns on and off
22
Q
GTP hydrolysis
A
converts GTP to GDP
same thing as GTP dephosphorylation (GDP results)
23
Q
GTP binding and hydrolysis
A
Bound GTP (Guanosine Triphosphate) turns a G-protein on
GTP hydrolysis turn it off
Does not involve phosphorylation
24
Q
Cell surface receptors
A
Allosteric activation of receptors
ligan-gated ion channels (i.e., neuronal communication)
25
Intracellular receptors
small, non-polar signaling molecules (i.e., steroids and estrogen) freely pass through the plasma membrane and activate cytoplasmic receptors
26
Fight or flight response
Adrenaline gets released
Rises blood pressure and glucose which provides body with oxygen and fuel
Adrenaline = glucose
27
Glycogen Phosphorylase
Breaks down glycogen to make glucose
28
G-protein coupled receptors
When a ligand binds to a g-protein coupled receptor, the receptor binds to and activates the G protein by replacing GDP with GTP
29
G protein subunits
α (alpha)
β (beta)
γ (gamma)
30
Activation of G proteins
Ligand binds to the G protein coupled receptor
Replaces GDP with GTP on α subunit (not phosphorylation)
GTP-Gα dissociates from the β and γ subunits and activates target proteins in the cell
Adrenaline binds to the β-adrenergic G-protein coupled receptor
Adenylate cyclase gets activated and Signal is terminated
31
cAMP
Cyclic adenosine monophosphate
Activates PKA (kinase A)
Second messenger to adrenaline, which is the "first messenger"
Adrenaline increases cAMP
32
Second messengers
Small, nonprotein, water-soluble molecules or ions that spread throughout a cell by diffusion
Cyclic AMP
Calcium ions
33
'cyclic' meaning
phosphate forms a circle with the 5' and 3' carbons in ribose
34
Kinase A
cAMP activates Kinase A to phosphorylate other proteins resulting in fight or flight response
Bonded to ligand binding pocket through hydrogen/ionic bonds
35
Kinases
Kinases phosphorylate other proteins
36
Simple Amplification
Each receptor activates multiple G proteins and adenylyl cyclase
Each AC makes many cAMP
Many Kinase As are activated
Each PKA activates multiple targets
37
Glycogen Synthase in F or F
Gets turned off
Stops the conversion of glucose to glycogen increasing glucose levels
38
Phospho-Glycogen Phosphorylase in F or F
Gets turned on
Phosphorylation of glycogen phosphorylase creates glucose
39
Glycogen phosphorylase kinase in F or F
GP kinase phosphorylates glycogen phosphorylase
GP kinase is phosphorylates by PKA
This turns it on
40
Termination of G protein signal
Adrenaline detaches from receptor
G protein converts GTP to GDP
cAMP is converted to AMP
Phosphatases remove phosphates added by kinases
41
Key steps of cell division in eukaryotes
Start with double strand of DNA
Cell grows and gets ready to replicate DNA
DNA gets replicated
Call grows and gets ready to divide
Cell divides into 2 identical daughter cells
42
Humans have ___ pairs of chromosomes for a total of ___
23, 46
43
Diploid
Have to versions of each chromosome
(i.e., humans - one from mom another from dad)
44
Homologous pair
a pair of the same chromosome
45
G1 Phase
Growth phase 1
Interphase
46
S Phase
Synthesizes DNA
duplicates chromosomes
Makes two chromatids
Interphase
47
Chromatids
Pair of exact copies of a chromosome
48
G2 phase
growth phase 2
get ready for division
Interphase
49
M phase
Cell divides into 2
Mitosis
50
Mitosis consists of
Prophase, Pro-metaphase, Metaphase, Anaphase, Telophase, and Cytokinesis
I PP MAT C
51
Prophase
sister chromatids are held together by the protein cohesin which is looped around and the centromere
Mitotic spindles made of microtubules start to form
52
Prometaphase
Nuclear envelope breaks down
Chromosomes randomly distributed
Microtubules start to capture chromatids at the kinetochores binded to the centromere
53
Metaphase
Each chromatid is attached to a microtubule
Microtubules are attached to spindle polls on opposite sides of the cell
Chromosomes get lined up in the middle of the cell
Spindle checkpoint
54
Anaphase
Cohesin is cut and chromatids separate into chromosomes
Chromosomes pulled onto opposite ends of cell
55
Telophase
Nucleus starts to reform
Chromosomes decondense
Motors and microtubules push the cell apart
56
Cytokinesis
Cell fully divides into two
Ends with two cells each with a complete identical copy of the chromosomes
57
Alleles
different versions of a gene
can have dominant and recessive
58
G0 Phase
When cells no longer divide they exit the cell cycle in G0
59
Cyclins
Proteins that go up and down at different steps in the cell cycle
Controls the massage through phases of the cell cycle
Regulates kinase
60
Cyclin-dependent kinases (CDK)
Concentration is constant
Phosphorylate other proteins to control protein activity
61
4 cyclins
G1 cyclin - activates cycle
G1/S cyclin - activates histone production
S cyclin - Activates DNA polymerase
MPF (M cyclin) - disassembles the nuclear envelope
62
Growth factors
mitogens
turn on the cycle
63
Mitogens
Bind receptor tyrosine kinases to activate Ras during G1
64
Ras
Induces Cyclin D (G1 cyclin) transcription which starts the cycle
65
Cyclin D (G1 cyclin)
Rises when growth factors activate Ras signaling pathway
Controls the expression of other genes needed to pass the next checkpoint
66
Cyclin E (G1/S cyclin)
Rises during G1 and drops during S phase
Activates Histone production
67
Cyclin E (G1/S cyclin) + a CDK
Prepares the cell for DNA replication by activating a transcription factor that creates the mRNA needed for producing histones
68
Histones
Protect DNA
DNA wraps around histones
Regulate gene expression by blocking RNA polymerase
Needed before DNA synthesis begins
69
Cyclin A (S cyclin)
Increases during S phase
Activates another CDK, which turns on DNA polymerase
70
Cyclin A (S cyclin) + a CDK
Activates DNA polymerase
Cyclin A initiates DNA synthesis by activating DNA polymerase
71
Cyclin B (M cyclin)
levels rise during mitosis which allows the formation of mitosis promoting factor (MPF)
72
Cyclin B (M cyclin) + a CDK
a Mitosis Promoting Factor (MPF)
Controls nuclear envelope structure through prophase and pro-metaphase
Phosphorylates lamin which causes it to disassemble
73
Lamin
A cytoskeletal protein that adds structure to the nucleus to provide protection to DNA
74
CDK concentration vs activity
CDK concentration is constant but its activity rises after cyclin concentration increases
75
What determines if a cell divides or not
Did the body tell the cell to divide and is the cell healthy enough to divide
76
External vs Internal signals
External signals (like growth factors) instruct cells to pass checkpoints
Internal signals determine if a cell should pass the checkpoints
77
G1/S checkpoint
controls cell size
Checks for:
molecular signals
size
Nutrients
DNA integrity
78
p53
senses DNA damage and cell health
DNA damage activates kinases that phosphorylate and turn on p53
activation of p53 blocks the cell cycle by blocking cyclin/CDKs
79
Active MAD
inhibits anaphase
Lack of microtubule attachment to a kinetochore activates MAD2 which inhibits APC (anaphase promoting complex) and thus anaphase
80
Separase
allows chromatids to separate
When all kinetochores are attached to microtubules MAD is inhibited and separase is activated by APC (anaphase promoting complex)
81
G2/M checkpoint
Checks if DNA is replicated and undamaged
82
Spindle checkpoint
checks that chromosomes are attached to microtubules
83
Chromosomes movement towards spindle poles
Can be pulled by the microtubules
Can move towards the poles through microtubule disassembly at the kinetochore
84
Replication bubble
two replication forks that move in opposite directions
85
Helicase
Unwinds the DNA duplex
86
Single-stranded binding proteins
Stabilize single strands of DNA
87
Topoisomerase II (DNA gyrase)
relieves the stress of unwinding
88
DNA polymerase (POL)
adds nucleotides to the 3' end of the daughter strand using the parental strand which is read towards 5' end
89
Leading strand
template strand gets read 3' to 5'
continuous elongation occurs at its 3' end
90
Lagging strand
Template strand is read 3' to 5'
Since elongation cannot occur on the 3' end, short stretches of NDA are made called Okazaki fragments
91
RNA primase
creates RNA with 3' end called an RNA primer
92
DNA Pol I
Replaces RNA primers with DNA
Proofreads new nucleotides and fixes its errors
93
DNA ligase
joins DNA fragments
Converts Okazaki fragments to a continuous strand of DNA
94
Clamp loader
coordinates activities
95
Telomeres
Protect the ends of dsDNA
Long telomeres mean the cell can divide many times (common in embryonic cells, stem cells, and cancerous cells)
Shorter telomeres make cell division limited (common in older cells)
96
Telomerase
Builds telomeres
Reverse transcriptase that generates DNA from an RNA template
97
How do mutations arise in relation to antibiotic experiment
randomly instead of in response to the antibiotic
98
What causes mutations
Anything that damages DNA
99
Mismatch repair
Fixes mutations
Mismatched bases are recognized because they change the shape of dsDNA
Enzymes break down DNA backbone
Exonuclease scans DNA looking for mismatches and removes the nucleotides
DNA polymerase fills the missing nucleotides using the intact strand as a template
DNA ligase connects the corrected strand
100
How do mutations alter transcription
If they change the DNA sequence in promoters, enhancers, or terminators they can alter gene expression
101
How can mutations alter mRNA processing
They can alter splicing, the formation of the 5' cap, the poly-A tail
102
How can mutations alter start or stop codons
If AUG is lost or created, translation starts there instead of where it should
If a stop codon is lost or created, translation ends there instead of where it should
Both alter protein length
103
How can mutations alter amino acids
if a codon changes, there can be no effect, a small effect, or a radical effect on protein activity
104
Silent mutation
Results in no change in the protein
synonymous
Determined by wobble
105
Missense
A mistake: simple and small
Makes a different amino acid
nonsynonymous
determined by wobble
106
Nonsense
Nothing is made afterward
a stop codon appears/is created (UAA, UAG, UGA)
107
Frameshift (Insertion or deletion)
Causes the latter half of the protein to have random amino acids by shifting the reading frame
108
Exons
Expressed gene regions
Joined together and translated into a protein by ribosomes
109
Intron
non-expressed region of DNA
Gets spliced out of mRNA so mutations here are harmless
110
conservative mutation
When an amino acid changes to one with similar composition, it might change the protein structure and activity, but it is also possible that it won't
111
Duchenne Muscular Dystrophy (DMD)
involves the disruption of dystrophin and has a severe negative effect on muscles
112
For X-linked diseases, why are females often carriers and males are usually affected?
Females are somewhat affected by these mutations because of x chromosome inactivation, but to a lesser degree
Females have two copies of the x chromosome
One good copy mostly prevents the disease
113
5'UTR
untranslated region before start codon (AUG)
114
3'UTR
Untranslated region after stop codon
115
Hemoglobin
Carries oxygen
116
Fetal hemoglobin
Has a higher O2 affinity which helps oxygen transfer from mother to fetus
Has slightly different subunits
Arose by duplication of a mutation
117
Chromosomal level insertion/deletions
This type of mutation can alter hundreds of genes
In duplications a region is present twice
In deletions a region is missing
Duplications are less harmful and can lead to evolution of new genes
118
Deletion of centromere
harmful because when the centromere is missing, microtubules can not attach to a kinetochore
cells get two or zero copies of a chromosome (lethal)
119
Inversions
When the regular order of a block of genes gets reversed
Don't change gene expression but can block recombination during gamete formation in meiosis
120
Reciprocal Translocation
Join segments from non-homologous chromosomes
Occurs in many cancers and leads to the expression of the wrong genes or chimeric proteins with abnormal function
121
Receptor tyrosine kinases (RTKs) (cancer)
Important for development, wound healing, insulin signaling, and cancer
most are single pass transmembrane proteins
122
Activation of Ras
Activated by RTKs
An adaptor protein (SOS) that binds and activates the RTK is a guanine exchange factor (GEF)
123
Small G proteins vs G proteins
Small G proteins are single proteins and are regulated by GEFs and GAPs
G proteins are regulated by B and Y subunits
124
Small G protein on and off switches
Off switch GAP = GTPase Activating proteins
On switch GEF = Guanine nucleotide exchanging factor
125
series of Mitogen-Activated Protein Kinases (MAP Ks)
A series of kinases are activated by Ras
Purpose is to amplify the signal then change gene expression
When Ras-GTP is converted to Ras-GDP, signal is terminated
126
Map K (Erk)
Activated by growth factors
Phosphorylates transcription factors that change gene expression
127
Mutated Ras
Causes cancer when over-activated/not turned off
128
Cancer
genetics + environment play a roll
Most arise when genes are altered by carcinogens and by errors in DNA replication and repair
129
Proto-oncogenes
normal genes that promote cell division but have the potential to cause cancer if mutated.
130
Oncogenes
are proto-oncogenes that have cancer-causing mutations
131
p53 (cancer)
tumor supressor
inhibits cell division
132
