MBLD Exam 2 Flashcards
(159 cards)
1
Q
What are the ways Acetyl CoA can be produced to enter the TCA cycle?
A
By sugars, fats, ketone bodies, keto- and gluco-genic amino acids.
2
Q
Which step in the TCA cycle can directly produced ATP?
A
Succinyl CoA –> Succinate
3
Q
_______ allow protons to leak back into the mitochondrial matrix by disrupting the integrity of the inner membrane, thereby eliminating the _____ gradient and ___ synthesis.
A
Uncouplers, proton gradient, and ATP synthesis
4
Q
DNP is considered a treatment used for:
1) ____
2) _____
3) ____
A
1) Cancer
2) Lyme disease
3) Diet aid
5
Q
2 essential Fatty acids:
1) ______ (w6) derived from seed oils.
2) _______ (w3) derived from fish oils
A
1) Linoleic acid
2) Alpha-Linoleic acid
6
Q
What are the main pathways of intermediary metabolism?
1) ____
2) ____
3) _____
4) ____
5) ____
A
1) Glycolysis
2) TCA Cycle
3) Urea cycle
4) Hexose monophosphate shunt (main pathway for generating NADPH
5) Triacylglycerol synthesis and degradation
7
Q
One molecule of Acetyl CoA (2 C) enters and two molecules of ____ are formed, i.e. no net loss or gain.
A
CO2
8
Q
Glycogen is the rapidly accessible storage form of ____, where it can be found in the ____ and ____.
A
Glucose
Found in the liver and muscle.
9
Q
Name the enzyme involved in Glycogen synthesis and breakdown.
1) _____
2) _____
A
1) Glycogen synthase
2) Glycogen Phosphorylase
10
Q
True/False: Gluconeogenesis is the reversal of Glycolysis.
A
False! Several unique steps overcome irreversible steps of glycolysis.
11
Q
Where does Gluconeogenesis primarily occur?
A
In the liver
12
Q
In what type of disease would you expect to find an increase in Gluconeogenesis resulting in elevated blood glucose?
A
Diabetes
13
Q
In lipid synthesis and breakdown, what is the key intermediate?
A
Acetyl CoA
14
Q
What is the process that Fatty acids may be broken down to Acetyl CoA?
A
Beta-oxidation
15
Q
Fatty acids are synthesized from acetyl CoA via _____.
A
Malonyl CoA
16
Q
_____ is also the key intermediate for ketone body synthesis and their breakdown product for entry into the TCA cycle.
A
Acetyl CoA
17
Q
Amino acids can be precursors for other nitrogen containing compounds: Name a couple of them.
A
Catecholamines (from Tyrosine) Porphyrin Histamine (from Histidine) Serotonin (from Tryptophan) Melanin Purines and pyrimidines
18
Q
What is the end product of aerobic glycolysis?
A
Pyruvate
19
Q
What are the three steps required for amino acid degradation?
A
Transamination, oxidative deamination, and formation of urea in the urea cycle.
20
Q
What is the structure of a 18:3(9,12,15) fatty acid?
A
18 carbons with 3 double bonds at positions 9, 12, and 15) from the carboxyl end.
21
Q
What is the main function of the hexose monophosphate shunt?
A
Generation of NADPH which is the main reducing agent of the cell
22
Q
How do defects in glycolysis lead to hemolytic anemia?
A
Lack of ATP from glycolysis prevents erythrocyte Na+/K+ ATPase from functioning, leading to intracellular accumulation of sodium, causing cellular swelling and rupture.
23
Q
In the Bohr effect, when there is a higher [H+] concentration, what type of allosteric effect do protons have on Hemoglobin and Oxygen binding?
A
Higher [H+], causes O2 release because a low pH stabilizes ionizable groups in deoxy Hb. Furthermore, decreased Oxygen affinity of Hb and shift to the right in the Oxygen dissociation curve. (See Goodnotes MBLD Exam 2)
24
Q
Another Bohr effect example, what type of allosteric effect does CO2 have on Hemoglobin and Oxygen binding?
A
Functions as a negative heterotrophic effector.
25
What type of effect does CO have on Hemoglobin and Oxygen binding?
CO will actually stabilize the R or oxy-Hb form (binds where Oxygen does) and functions as a positive Homotropic effector. It won't let go of CO because it has a high affinity for it (hence the positive)
26
The N-terminal glycosylation of HbA will produce _____, and the effect from there regarding oxygen binding is: (explain)
HbA1c (glucose in Hemoglobin), HbA1c "T" state exhibits tighter O2 binding than normal, leading to slower O2 dissociation.
27
In the family of B7 ligand on APCs, there are two such called: PD-L1 and PD-L2 that will bind to the receptor, ______ of activated T cells, and this binding will ____ the function of T cells.
Receptor: PD-1
| Binding will inhibit T cell function (activation)
28
Name two T cell inhibitory signals within the CD28 family: 1)____ and 2)_____
1) CTLA4
2) PD-1
(Goodnotes Exam 2 MBLD T Cell inhibitory signals)
29
The TCR on a naive CD8 T cell binds to a viral peptide bound to MHC I on an epithelial cell. What happens?
Epithelial cells do NOT express costimulatory molecules, so T cell does not receive second signal and does NOT get activated.
30
The TCR on a naive T CD8 T cell bind to a viral peptide bound to MHC I on an activated dendritic cell which also expresses CD80 (B7-1) and CD86 (B7-2). What happens?
Activated dendritic cells express MHC and costimulatory molecules, so T cell receives two signals and is activated.
31
After having received the signal through the TCR and CD28, the CD8 T cell is activated. The TCR on the activated CD8 T cell binds to a viral peptide bound to MHC I on an epithelial cell. What happens?
Once activated, the CD8 T cell only needs to bind to MHC-peptide on the target cell. The CD8 cell will kill the virally-infected epithelial cell.
32
In isotype switching VDJ region ______.
Remains the same!
33
_______ facilitate formation of DNA loops which are lost from genome --> after isotype switching B cell cannot go back to making ____.
```
Switch Regions (S)
IgM
```
34
___: Isotype on the surface of mature, naive B cells, secreted in early, acute primary infection.
IgM
35
___: secreted late in primary infection and in secondary infection, most abundant isotype in blood.
IgG
36
Isotype responsible for Opsonization and phagocytosis; complement activation; neonatal immunity (placenta transfer): ____.
IgG
37
True/False: Naive T cell is able to bind its CD40L to CD40 on an APC.
False! Not yet! Don't fall for it. (Goodnotes T and B cell activation lecture)
38
Name an example of a drug that can interact with enzymes in the extracellular space.
ACE inhibitors
39
True/False: the Occupancy model (AKA drug effects) is directly proportional to the [Drug-Receptor] complex concentration.
True
40
____: Amount of drug required to produce response, a function both of affinity and efficacy.
Potency of a drug!
41
Competitive vs Non-competitive antagonists: Which reduces agonist potency, and which reduces agonist efficacy?
Competitive antagonist: reduces agonist potency
| Non-competitive antagonist: reduces agonist efficacy.
42
Name an example of a drug that is considered a partial agonist.
Beta-blockers: the effect to a certain extent and that's it. Low efficacy!
43
Dose-response curves can be ______ (i.e. evaluate extent of a response) or _____ (i.e. quantify the population who experience a response at a given dose)
1) graded
| 2) quantal
44
_____: affect only cells adjacent to the cell producing the signal.
Juxtacrine signaling
45
Peptide and amine hormones bind to cell ______ and initiate cascade response, but Lipophilic ligands can bind directly to receptors located where?
Cell surface receptors,
| Lipophilic bind directly to receptors across the cell membrane and into the nucleus.
46
In the two types of cellular responses, what are the changes that can be made to result in an altered cytoplasmic machinery?
1) Altered protein function--changes in activity or function of specific enzymes and other proteins that preexist in the cell.
2) Altered protein synthesis--changes in the amounts of specific proteins produced by a cell, e.g. by modifying transcription factors that stimulate or repress gene expression.
47
How does Lithium work as a psychoactive drug? Where in the GPCR signaling does it affect?
1) It inhibits G protein activation of phospholipase C.
2) Inhibits the synthesis of IP3
In both cases brain activity is returned to normal.
48
Key Facts about G proteins and human disease:
1) __: in intestine is perpetually turned on in cholera
2) ___: in lung is permanently turned off in pertussis infection.
3) __: is deficient in retinitis pigmentosa and inactive in night and color blindness.
4) ___ is defective in neonatal severe hyperparathyroidism and hypercalcemia.
1) Gs
2) Gi
3) Gt
4) Gq
49
Which signaling pathway utilizes autophosphorylation on tyrosine residues to dock adaptor proteins, further activating Ras through GTP binding?
Receptor Tyrosine kinases
50
The mitogen activated protein kinase (MAPK) cascade is initiated by _____ binding of soluble ___, which is activated by phosphorylation.
Ras-GTP binding
| Raf
51
Every step in receptor tyrosine kinase signaling will have a ______, to PREVENT over-proliferation of a cell (ie. cancer)
Phosphatases
52
From an activated Akt kinase to mTOR, what are the three pathways from mTOR?
Increased glucose uptake
Increased glycolysis
Increased protein synthesis.
53
If you were a cancer cell, what are some kinases/proteins that you would want turned on in order to thrive and proliferate?
```
On:
mTOR
Akt
IAPs
cFLIP
USURPIN
Amplification of EGF-Her2
Ras (monomeric G-protein)
```
54
Insulin uses what type of receptor for signaling?
Receptor Tyrosine Kinase (RTK)
55
Glycogen breakdown in the liver utilizes two types of GPCRs: 1) _____ and 2) ____.
G-alpha-q and G-alpha-s
56
Glycogen metabolism is controlled by two enzymes, 1) ______ and 2) ______
1) Glycogen synthase
| 2) Phosphorylase
57
Insulin and adrenalin have opposite effects on glycogen synthesis: insulin promotes glycogen synthesis by activating _____ and by inhibiting ____ by the _____ pathway.
1) ISPK/PP1G
| 2) GSK-3beta by the 3) P13K/PKB pathway.
58
Adrenalin in glycogen synthesis, inhibits _______ by the _____ pathway.
Glycogen synthesis by the cAMP/PKA pathway.
59
ACh in skeletal muscle and adrenalin in liver activate phosphorylase kinase by a common mechanism, an increase in _____, although the effect of ACh is by ______ and that of adrenalin by _____ channels.
1) cytosolic Ca2+
2) Voltage dependent channels
3) IP3-gated Ca2+ channels
60
An example of a pathway using JAK/STAT tyrosine kinase, would include: (x4 cytokines) (x3 hormones)
4 cytokines: IFN-gamma, IFN-alpha, and IFN-beta
| 3 hormones: Growth hormone, leptin, and erythropoietin
61
True/False: There is diversity among the JAK/STAT pathway in which there exists different isoforms.
True
62
In Hypoxia signaling, there is a need for induced erythropoietin, what type of signaling pathway does erythropoietin use?
Recall: JAK/STAT pathway
63
In Hypoxic conditions, does PHD (Proline hydroxylase) get activated, furthering the hydroxylation of HIF-1alpha by VHL?
NO! Without oxygen, PHD cannot be activated, leading to HIF-1alpha to freely bind DNA and regulate transcription of target genes.
64
Even after an activated HIF-1alpha gets through to nucleus to bind DNA, there is another regulation site that can hydroxylate it before it can bind. What is it called?
Asparagine hydroxylase = no gene expression
65
Immunity due to vaccines against Poliovirus and Hep A and B utilize the _____ effector mechanism blocking those microbes.
Neutralization
66
Fc receptor that has high affinity Macrophages, Neutrophils (phagocytosis/activation)
Fc-gammaRI
67
Fc receptor by mast cells leading to immediate hypersensitivity (IgE).
Fc-epsilonRI
68
Fc receptor by NK cells, Macrophages, dendritic cells (ADCC)
Fc-gammaRIIIA
69
Fc receptor by mucosal epithelial cells.
Poly IgR
70
Fc receptor by Placental epithelial cells.
FcRn (IgG to placenta)
71
Mucosal Associated Lymphoid Tissue in the gut utilizes the ____ to transcytose IgA.
M cell
72
Through the Antibody Dependent Cell-mediated cytotoxicity (ADCC) by NK cells, they release what two killing enzymes?
1) Perforin
| 2) Granzymes
73
What two killing enzymes are usually associated with Neutrophils in terms of ADCC?
Lytic enzymes and TNF
74
Mutations in OI (genes COL1A1, COL1A2) could produce _____ chains that ____ triple helix formation or amino acid substitutions that _______ intrastrand and inter strand bonding collagen.
shortened chains that prevent triple helix formation.
| destabilize
75
Ehler-Danlos is due to collagen defects from?
Issues with post-translational modifications (Hydroxylation) or in failure to secrete collagen.
76
Viruses vs. viroids: With the example of Adenoassisted virus, and Hepatitis D, what is a viroid?
AKA Satellite viruses require other viruses that provide essential components for their replication not provided by the host cell.
77
Recall: Replication requires __________ that amplifies (-) sense intermediate RNA into genomic (+) sense RNA.
RNA-dependent RNA Polymerase
78
What is a capsid?
The protein shell that surrounds the nucleic acid of the virus, consisting of individual capsomers.
79
What is the viral envelope?
A lipid bilayer derived from a cellular membrane (often the plasma membrane) that surrounds the capsid of enveloped viruses.
80
What are the hallmarks used to classify viruses?
Type and structure (and sense for single-stranded RNA viruses) of nucleic acid, morphology of capsid, and presence of envelope.
81
Histology: Hematoxylin is a ____ dye and stains ____ structures.
Basic dye and stains acidic structures
82
Histology: Eosin is a ___ dye and stains _____ structures.
Acidic dye and stains basic structures.
83
Name of staining for muscle/collagen.
Masson Trichrome stain
84
Name for staining for elastic fibers/collagen where muscle stains yellow.
Van Gieson (Elastic) stain
85
Name of staining for reticulin fibers (collagen Type III).
Reticulin stain
86
In Bona Marrow stains, within immature WBC and RBCs, what is the appearance of the nuclei?
Blue to violet.
87
In Supravital stains and methylene blue, what is it staining?
Reticulocyte (immature RBC) staining the ribosome pattern.
88
What is the staining called where you can see iron deposits in cells, where the staining is blue/dark blue/black?
Prussian Blue/Perl's Stain
89
Name of the staining where specific antibody for specific antigens/protein/immune complex is shown.
Immunostains (can be immunohistochemistry or immunofluorescent)
90
Term used for microscopic study of "diseased" tissue.
Pathology
91
In Fine Needle Aspiration Cytology (FNAC), how is the biopsy retrieved?
Finding a nodule within the body (near the surface or not too deep) with a fine needle to retrieve fluid for biopsy.
92
What are the four basic tissue types?
Epithelial tissue, connective tissue, muscle tissue, and nervous tissue.
93
True/False: Cell junctions are usually seen on H&E stained tissues.
False, they usually are NOT.
94
What would happen if there is a loss of/dysregulation of cell junctions?
In cancer, deregulated cellular tight junctions, result in uncontrolled proliferation of cells. There is disruption of homeostasis: results in altered signaling at cell-cell junctions - may lead to dehydration, loss of nutrients, etc.
95
Which viruses replicate in both the cytoplasm and nucleus of the cell?
Retroviruses and Hepadnaviruses
96
Cascade initiated by trans-activator in viral gene expression using cell transcription machinery: ______.
Alpha-TIF AKA VP16
97
In viral gene expression: all are expressed by host _____, and are comprised of the cascade Alpha (____), Beta, (_____), and Gamma (_______).
RNA Pol II
Alpha - Regulatory proteins
Beta - DNA replication
Gamma - Structural proteins
98
_______: is reduced virulence/pathogenesis.
Attenuation
99
True/False: The degree in which virulence is measured is by the rate of onset of symptoms or replication efficiency of a virus.
False! It is indicative of the ability of a pathogen to establish a productive infection due to presence of factors. Ex: Spike protein on virus contributes to its virulence.
100
What is the component of HIV that counteracts the cell's APOBEC's deamination?
vif
101
One of HIV's major genes is ___, which encodes matrix and core proteins (p24, p17)
gag
102
Another one of HIV's major genes is ___, which encodes reverse transcriptase, protease, integrate, and ribonuclease.
pol
103
Another one of HIV's major genes is ___ which encodes envelope proteins. gp160
env
104
What does gp160 cleave to?
gp120 and gp41
105
When gp120 is bound to CD4, what now can CD4 not recognize?
The MHC-peptide antigen presentation!
106
Viral ___ protein can interfere with host transcription, it can cross the plasma membrane and enter uninfected T cells.
Tat
107
Within flow cytometry, what is the normal ratio of CD4:CD8?
2:1
108
Aside from Reverse Transcriptase Inhibitors (Drugs), list the mnemonic and drugs for ALL relevant antiviral drugs.
Mnemonic: ME-AR-AZE-R SR-ZO (Mearazer srzo)
109
Antiviral Attachment drugs: (2)
Attachment: Maraviroc and Enfuviritide (T-20 [Maybe MT-ARAZER SRZO])
110
Antiviral Ion channel blocker drugs: (2)
Ion channel blockers: Amantadine and Rimantadine
111
Antiviral Polymerase inhibitor drugs: (3)
Polymerase inhibitors: Acyclovir, Zidovudine, Efavirenz
112
Antiviral Integrase inhibitor drugs: (1)
Raltegravir (others to recognize: Elvitegravir and Dolutegravir)
113
Antiviral Protease Inhibitor drugs: (2)
Protease inhibitors: Saquinavir and Ritonavir
114
Antiviral Neuraminidase inhibitor: (2)
Neuraminidase inhibitors: Zanamivir and Oseltamivir
115
True/False: Enfuviritide (T-20) would be a good 1st line drug to administer for inhibition of attachment.
False, it would not be a good drug for that because it is a polypeptide drug that will be administered subcutaneously. Side note: it prevents FUSION of HIV and cell membranes.
116
Maraviroc, an oral drug, _______ CCR5 receptors to prevent HIV ___ protein binding.
Antagonizes CCR5
| HIV gp120 protein binding
117
Before prescribing Maraviroc, what must be done first? Any tests?
Yes, you must first test that the HIV strain is only CCR5-tropic and cannot enter cells through CXCR4.
118
Another good drug to note is: _______ (a post-attachment entry inhibitor) "mab" against domain 2 of CD4, which prevents gp120 from interacting with co-receptors CCR5 or CXCR4 AFTER binding to CD4.
Ibalizumab
119
What is a class of drug inhibitors toward HIV reverse transcriptase?
Nucleotide/Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
120
Antiviral drugs for Reverse Transcriptase! Mnemonic and how many are there to know?
LETZA (5) to know.
121
Reverse Transcriptase Inhibitor drug that has the least inhibition of DNA polymerase gamma: _____.
Lamivudine (3TC)
122
Reverse Transcriptase Inhibitor drug that is a derivative of Lamivudine, but the advantage is daily dosing.
Emritricitabine (FTC)
123
NRTI drug that is administered as a prodrug, and must undergo further phosphorylation before inhibiting reverse transcriptase: ______.
Tenofavir - a nucleotide
124
What is the first NRTI, but is not commonly first line these days because it can produce effects like myelosuppression (anemia, neutropenia)? Inhibitor of cellular Thymidine Kinase!
Zidovudine (AZT)
125
If a patient has a mutation HLA B*5701, they are much more likely to develop ______ hypersensitivity syndrome. What are the symptoms that can manifest?
Abacavir
| Symptoms: fever, rash, GI complaints, etc)
126
What adverse effects arise due to inhibition of mitochondrial DNA Polymerase gamma?
```
Lactic acidosis
Hepatitis (micro vesicular)
Pancreatitis
Peripheral neuropathy
Lipodystrophy (also seen with protease inhibitors)
```
127
Inhibition of DNA polymerase gamma impairs ______ (pathway).
Oxidative Phosphorylation
128
Which antiviral drug that you know of so far, can inhibit mitochondrial DNA polymerase gamma?
Abacavir
129
Among the NON Nucleoside Reverse Transcriptase Inhibitors (NNRTIs), what is the mnemonic and how many to know?
NEEP (4)
| Efavirenz, Nevirapine, Etravirine, and Rilpivirine
130
Are NNRTIs incorporated into the DNA?
No, they bind NEAR the catalytic site of Reverse Trascriptase
131
Which type of antiviral drugs are contraindicated in pregnant women?
NNRTIs
132
Ritonavir is a potent ______ inhibitor, and is often given just so it can do what?
CYP3A4
| "Boosting with Ritonavir" and mix with other drugs
133
Explain what can be included in General Antiviral drug therapy, as far as drug options and how many are usually given together.
Common backbones (NRTIs) x2 + 3rd drug (NNRTI, Protease inhibitor, or integrate inhibitor)
134
Use of Ritonavir can produce an undesirable effect toward _______ disease, because of _____ inhibition.
Cushing disease
| CYP3A4 inhibition
135
Know relation in Solute partition coefficient equation: k = [Coil]/[Cwater]
More oil concentration means larger value for k, and faster movement through the bilayer.
136
Solute Diffusion Coefficient: D = KT/6(pi)rn. Know relations here. What do I need to focus on in this equation?
Focus:
1) How large the molecule is
2) How viscous it is too
137
Solute Permeability: P = kD/Dx. Know relations here. What equations are used here?
Recall solute's partition coefficient and solute's diffusion coefficient. (k and D) Basically, those two coefficient's are directly proportional to Permeability, but the farther the distance to travel for a molecule, this will lower Permeability.
138
Using Fick's Law, one can calculate two things: 1) ____ and 2) ____.
1) net Rate of diffusion
| 2) Direction of diffusion
139
What will happen if we get a large surface area cell, how will that impact diffusion?
The larger the surface area, the more area it will take to cross the bilayer, which will slow the process down.
140
Does Facilitated diffusion require ATP?
No, more so it relies on uriporters, antiporters, and symporters.
141
True/False: We can use Fick's law pretty easily in terms of facilitated diffusion.
False, there are severe limitations. Works well with Simple diffusion
142
True/False: Facilitated diffusion is usually with the gradient.
True
143
What type of drugs inhibit Na+/K+ ATPase in primary active transport?
Cardiac glycoside (Digitalis) and Ouabain
144
Osmolarity equations: Osm = ________
```
Osm = gC
g = # particles/mol in solution
C = concentration
```
145
Van't Hoff equation pertains to __________. What is the equation? pi = _________
osmotic pressure
| pi = gC(sigma)RT
146
What are ways to break the phosphate bonds of ATP? What is needed to break them?
Water (H2O) and ATPase
147
When Uncouplers are mentioned, that should prompt you to think of it in terms of?
Uncouplers allow protons to leak back into the mitochondrial matrix to eliminate the proton gradient and ATP synthesis. So think of ETC and mitochondria!
148
DNP helps the mitochondrial respiration ______, generating intracellular ______.
Speed up
| Hyperthermia
149
Within the ETC, protons are ONLY pumped into what complexes?
Complexes I, III, and IV
150
In terms to how Oxygen binds to Hb, the more Oxygen that binds to it, increases ______.
Cooperativity
151
Does Mb have cooperativity like Hb does?
No! it only has one O2 molecule.
152
How would cooperativity appear on an oxygen dissociation curve graph?
It would appear sigmoidal
153
What is the Nernst equation? What does it determine?
E(ion) = (60/z)(log [ion]out/[ion]in)
E(ion) = equilibrium potential for ion
z = ionic valence
Determines the electrical force required to just balance a gradient force.
154
How does Resistance affect the conductance and permeability?
More resistance will decrease conductance AND permeability
155
What toxin will inhibit voltage-gated Na+ channels?
Tetrodotoxin (TTX)
| Sushi anyone?
156
In order to cross the blood brain barrier, drugs must be: (3)
1) Non-protein bound
2) Non-ionized
3) Highly lipid soluble
157
In Hypoxia signaling, goes through the cell membrane to control the activity of a transcription factor through _________ modification and by _________.
Covalent modification and any hydroxylation.
158
Two drugs involved in anticancer drugs that inhibits DNA synthesis: 1) is a suicide inhibitor and 2) the other one is a competitive inhibitor. What are they?
1) 5-Fluorouracil
| 2) Methotrexate (other is Aminopterin)
159
Would an increase in CO be a (+) homotropic effector or a (+) heterotrophic effector? Furthermore, would it relax or tighten the oxyHb form?
CO has GREAT affinity for Hb, more than O2.
And it also binds at the SAME site that oxygen does, so it would be a (+) homotropic effector. When CO binds the oxyHb, it would relax the form, holding tightly onto CO, making it difficult to dissociate, and difficult for O2 to bind and get delivered.
