The Biochemistry Of Human Cells Flashcards
1
Q
JAK/STAT Pathway Purpose
A
Stimulate hematopoietic cell growth and proliferation.
2
Q
JAK/STAT Pathway Ligand
A
Cytokines. (Interferons and Interleukins)
3
Q
JAK/STAT Receptor
A
Cytokines receptor coupled to JAK
4
Q
JAK/STAT Transduction Events
A
JAK autophosphorylates. It then binds STAT. STAT is then phosphorylated.
5
Q
JAK/STAT Target
A
Phosphorylated STAT is an active transcription factor which enters the nucleus and turns on transcription of specific cytokines response genes.
6
Q
RAS-MAPK Pathway Purpose
A
Stimulate cell growth and proliferation.
7
Q
RAS-MAPK ligand/ first messenger
A
Growth factor
8
Q
RAS-MAPK receptor.
A
Tyrosine kinase receptor.
9
Q
RAS-MAPK Transduction Events
A
RAS is activated by GTP exchange factor (GEF) which then in turn activates RAF.
10
Q
RAS-MAPK Amplification Events.
A
RAF phosphorylates MEK. MEK phosphorylates ERK
11
Q
RAS-MAPK Target.
A
ERK (MAPK) phosphorylates a number of target proteins and transcription factors.
12
Q
cAMP-PKA Pathway purpose
A
Stimulates transcription of genes encoding for (among other things) regulators of metabolic pathways.
13
Q
cAMP-PKA ligand/first messenger.
A
Peptide hormones. (Epinephrine)
14
Q
cAMP-PKA Receptor
A
7 transmembrane receptor.
15
Q
cAMP-PKA Transduction Events
A
Receptor activates large G Protein which activates adenylate cyclase stimulating cAMP production.
16
Q
cAMP-PKA Amplification Events
A
cAMP activates PKA by stimulating dissociation of regulatory subunits.
17
Q
cAMP-PKA Second messenger
A
cAMP
18
Q
cAMP-PKA Target
A
PKA. Enters nucleus and activates transcription factors.
19
Q
P13K-AKT Purpose
A
Controls cell growth and apoptosis pathways.
20
Q
P13K-AKT ligand/first messenger
A
Selected hormones (insulin), growth factors, cell survival ligands
21
Q
P13K-AKT receptor
A
Receptor dimers with intrinsic kinase domains or that bind intracellular kinases.
22
Q
P13K-AKT transduction Events
A
Receptor is phosphorylated which in turn stimulates the conversion of PIP2 to PIP3. PIP3 stimulates PDK1 which activates AKT(PKB)
23
Q
P13K-AKT Target.
A
Apoptosis control proteins, transcription factors, translation factors and cyclins
24
Q
What is the negative regulator of the P13K-AKT Pathway
A
PTEN. Phosphatase and tensin homolog. Deleted in many cancers leading to inhibition of apoptosis.
25
IP3-PKC Pathway Purpose
Selected growth factors. Mitogens. Immune signals (histamine).
26
IP3-PKC receptor
Usually a 7 transmembrane receptor
27
IP3-PKC transduction Events
Receptor activates a large G Protein. G Protein activates phospholipase C. Phospholipase C cleaves PI4,5 bisphosphate to produce IP3 and DAG.
28
IP3-PKC Amplification Events
IP3 binds to smooth Er calcium channels and stimulates the release of calcium. Calcium binds to PKC (which is anchored by DAG) and activates PKC
29
IP3-PKC target.
PKC phosphorylates a wide variety of substrates including nuclear transcription and cytoplasmic regulatory proteins.
30
How does Rigosertib work?
Inhibit activation of RAF by RAS. This prevents the amplification with MEK and ERK effectively silencing it
31
Explain the activation and inactivation of monomeric (small) G Protein.
Activation: GEF removes GDP and inserts GTP
Inactivation: GAP removes a phosphate.
32
What is a neoplasm?
New growth.
33
How does RAS pathway lead to neurofibromatosis
Mutation in NF1 gene. NF1 normally returns RAS to an inactive GDP bound state. When NF1 is mutated, RAS cannot be inactivated and may result in uncontrolled growth
34
Which amino acids can be phosphorylated?
Tyrosine. Threonine. Serine.
35
How can we prevent cancer from ErbB-2 Receptors in Ras Pathway?
Using human monoclonal antibodies to Erb-2 (Herceptin) to block binding of growth factors to receptor
36
Give an example of a molecule PKA activates
CREB (transcription factor)
37
What does Protein Kinase B do?
Also known as AKT it regulates cell proliferation, growth, and death
38
What does PTEN do?
It is a negative regulator of the PI3K-AKT Pathway. As a phosphatase, it converts PIP3 back into PIP2
39
Membranes are comprised of
lipids proteins and carbohydrates
40
What are integral membrane proteins?
Have a hydrophobic portion of their structure buried in the bilayer
41
What are peripheral membrane proteins?
Associate with the membrane through interactions with integral membrane proteins.
42
What is a membrane?
sheet like lipid bilayer
43
What is a liposome?
spherical lipid bilayer
44
What is a micelle?
spherical single lipid layer structure with polar regions facing out
45
What are exosomes and how can they be used?
They are types of vesicles and can be utilized for the detection of biomarkers before imaging or other detection methods
46
What are channels?
they move substances across the membrane via passive diffusion driven by concentration gradients
47
What are pumps?
They move substances across membranes by active energy dependent transport
48
How does the NA/K Pump Work?
Pumps in 2 K+ ions and pumps out 3 NA+ ions. Driven by ATP.
49
What is a synporter?
Transporter coupled to other transporter. Moves two substances in same direction across the membrane.
50
What is an antiporter?
Transporter coupled to another transporter. Moves two substances in opposite directions across the membrane.
51
What is an ABC transporter and what is its significance to Cancer?
It is a transporter that binds 2 ATP and through their hydrolysis causes a conformational change which expels the ligand into the extracellular space. It is relevant because cancer cells may develop resistance by evolving to utilize these transporters to pump chemo drugs out of the cell.
52
The nucleus is contiguous with which organelle
Rough ER
53
What are the two ways substances can get in and out of the nucleus?
Diffusion= small
| Through Nuclear Pore Complexes utilizing Nuclear Localization Signals= large
54
Where is protein synthesized?
On ribosomes. Either on free ribosomes if they will be used in the cell or on bound ribosomes if the protein is an integral membrane protein or a secreted protein.
55
What is the largest membranous system in the cell and what does it do?
ER. post-translational modification in rough ER. CA2+ storage, synthesis of lipids, steroids, carbs, and modification of toxic molecules in smooth ER.
56
How are secreted and integral membrane proteins inserted into ER?
The newly formed polypeptide produces a signal peptide. This binds to a Signal recognition peptide. This SRP then binds to a site on the RER near a pore called a translocon. The signal sequence is removed and the growing polypeptide chain is extended into the RER.
57
How are proteins packed into vesicles?
In the RER secreted and other soluble proteins are packaged into the lumen of the vesicle while integral membrane proteins reside in the vesicle membrane.
58
Order of organelles passed through by a protein on its way to the surface
RER, Golgi, Membrane
59
How are properly folded proteins in the ER identified?
The cell produces exit signals on cargo receptors. These receptors are bound by functional proteins. Misfolded proteins are marked by chaperone proteins.
60
How are misfolded proteins dealt with?
They are bound by chaperones and ejected into the cytosol where they are identified by N-glycanase and bound by ubiquitin. Ubiquitin marking allows proteosomes to digest the misfolded protein and recycle it for peptides and amino acids.
61
What is the lysosomes function?
To digest protein, nucleic acid, lipids and polysaccharides using acid hydrolases.
62
Name 3 lysosomal storage diseases
Tay Sachs- A.Jews
Gauchers- A. Jews
Metachromic Leukodystrophy- Navajo
63
Explain mutation causing cystic fibrosis
CFTR gene mutates. CFTR is a is a transporter of Cl- in and out of the cell in sweat glands and airway. When it does not work excess Na+ may enter the cell. This in turn forces water into the cell which dehydrates mucus and allows bacterial infection. Also sterilizes males.
64
how do vesicles know where to fuse?
```
vsnares= vesicle receptors
tsnares= target receptors
```
65
How does botulism toxin work?
It is a bacteria (clostridium botulinum) which cleaves snare proteins and prevents vesicles from finding fusion targets. this in turn blocks neurotransmitter release from these vesicles.
66
What are two types of mutations?
Gain of function
| Loss of function
67
What are the primary 3 carbs in our diet?
Starch
Sucrose
Lactose
68
What is the difference between starch and cellulose.
A single B1-4 linkage on cellulose
69
List the steps in the digestion of carbs
1) salivation
2) A-amylase
3) stomach= mechanical
4) pancreas= secretion of enzymes
5) chemical digestion in small intestine
70
What are the 3 types of sugars we break down carbs into
glucose, fructose, galactose
71
Why does starch help with good poop?
Hydroxyl group on sugar rings binds water readily.
72
Why is 2,4 dintrophenol not a great drug to take for weight loss?
even though it facilitates the diffusion of H+ back across the gradient which technically makes you work harder for energy.. it also will cause all your organs to fail.
73
What is SGLT-1. What does it do?
It is a sodium-glucose transporter. It is a synporter which transports sodium and glucose both into the cell using the sodium gradient generated by the Na/K pump.
74
What is Glut5 and what does it do?
transports fructose into the cell.
75
What is cholesterol used for?
used in the stabilization of the membrane to keep it fluid in large temperature fluxes. Also used for vitamin D synth.
76
explain hypercholesterolemia and how it can kill you.
genetic mutation that prevents the internalization of LDL by the liver. LDL stays in blood stream. Is oxidized by macrophage. creates foam cell. smooth muscle migrates and proliferates to site. platelets create thrombus. Thrombus may detatch and create embolus.
77
Chylomicron FA are uptaken by which tissues
mammary, cardiac muscle, adipose then the liver and turned to LDL
78
function of LDL
send FA through the bloodstream again for uptake by peripheral tissue
79
function of HDL
give LDL one last chance to get cholesterol to tissues. Then to transport cholesterol out of circulation for recycling into bile salts
80
What are the step of Lipid digestion?
Emulsification by bile salts from gall blader.
lipase from pancrease cleaves 2 FA
uptake via transporters (ATP independent)
Reformation of FA
Loaded onto apoB48
81
What do statins do?
HMG CoA reductase inhibitor. May be used to reduce the level of LDL in patients. Blocks cholesterol synthesis. But then somehow also can be used to treat cancer. Not fully understood.
82
What is a gene?
A segment of DNA on a chromosome (nuclear and mitochondrial) that encodes a functional RNA
83
What is a genome?
The entire complement of DNA in an organism.
| This includes nuclear DNA, mitochondrial DNA
84
How big is the human haploid nuclear genome?
3 billion. Roughly. BP
85
Definition of exome.
Sequence of the expressed region of a genome that encode for functional proteins and ncRNAs (exons).
86
What are the 3 Categories of repeats.
Simple sequence. 10%
Retrotransposons. 42%
DNA transposons. 3%
87
What are Mini Satellites?
Clusters of up to 20 KB in length with repeat units of 25bp.
88
What are Micro Satellites?
Clusters of less than 150 bp with repeat units of fewer than 13 bp. Most common are CA repeats used in paternity testing.
89
What are LINES and SINES?
Long interspersed nuclear elements
| Short interspersed nuclear elements
90
What are the two ways DNA transposons move?
Conservative transposition= excision and reinsertion
| Replicative transposition= remain in original place. Copy inserted to new position.
91
How are chromosomes identified?
Isolated in the metaphase part of mitotic division. Identified by size, position to centromere, and giemsa staining.
92
What is the epigenome?
Heritable changes in the genome and its expression that do not involve change in the sequence of DNA.
93
How are histones modified?
Covalent modifications on the tails of histone proteins.
| This "marking" may change the affinity of certain histone conformations.
94
What is euchromatin?
Uncoiled transcriptionally active chromatin.
95
What is heterochromatin?
Densely packed transcriptionally inactive chromatin.
96
What does DNA methylation do?
Methyl attaches to cytosine residue. Turns off genes by attracting histone modification enzymes and remodeling proteins. Effectively silencer.
97
What is the process for demethylation?
Methylcytosine is changed to hydroxymethylcytosine. Then the methyl alcohol is removed by an enzyme.
98
What is transgenerational epigenetic inheritance.
Controversial new hypothesis that postulates that epigenetic marks in parental gametes due to exposure are not completely erased and may be transferred to offspring.
99
What is circulating free DNA?
DNA that has been liberated from opened human cells, microbiome, tumors, fetus, transplanted organs?
Can be used in preclinical cancer diagnosis and monitoring.
100
What is melanoma?
Highly metastatic and treatment resistant cancer originating in melanocytes in the epidermis.
101
What kinda of melanoma did Bob Marley have and what is unique about it?
Acral lentiginous melanoma. Found in less than 2% of the population. Not correlated with sun exposure. Instead is believed to be caused by inherited germline mutations.
102
What do cells do?
Transform energy, respond to stress, communicate, move
103
Are there more eukaryotic or prokaryotic cells in the body?
Prokaryotic. About 10x more
104
What is totipotent?
Stem cells which make up the zygote initially. Can turn into an entire person
105
What is pluripotent?
Can give rise to any cell but not all cells.
106
What is multi potent?
A stem cell that can give rise to a range of cell types. Adult stem cells found in multi potent tissues
107
What is a unipotent cell
Cell can only give rise to a single type of cell. Satellite cells in muscle for example.
108
What is an induced pluripotent cell?
A differentiated cell which has been transfected with genes encoding specific transcription factors
109
The blastocyst gives rise to which 3 tissue types.
Ectoderm
Mesoderm
Endoderm
110
What are symmetric and asymmetric cell division.
A cell producing two of the same cells.
| A cell producing one differentiated cell and one stem cell.
111
Malignancy is characterized by
Mutations in key genes.
| Hypertrophy or hyperplasia.
112
Intrinsic causes of apoptosis and main intermediaries.
Stress radiation and chemicals. P53 leads to Caspase 3
113
Extrinsic causes of apoptosis and main intermediaries.
Ligands. CD95 leads to Caspase 3.
114
What's Lamellipodia?
Actin mediated crawling
115
Rolling
Cells on a blood vessel lumen, mediated by selectin, same as leukocytes
116
What are tight junctions?
Near apical side of epithelial cells. Composed of branching mesh-like Protein. Claudins and Occludins.
117
Adherens Junctions
Form a belt connecting actin cytoskeleton of adjacent cells.
Cadhedrin proteins. Alpha and beta catenin attached to actin. E cadhedrin loss may lead to metastasis.
118
Desmosomes
Interlocking Protein complexes linking intermediate filaments to ECM.
119
Gap Junctions.
Directly connect the cytoplasm of two cells.
| Connexin proteins. Occur everywhere except skeletal muscle and mobile cell types.
120
What is the importance of the ECM and Integrin in signaling.
ECM facilitates cell contact and integrity connect the actin cytoskeleton to ECM
121
What does methyl transferase do?
Makes sure DNA is methylated even after replication.
