Histology 1 & 2 Flashcards
(183 cards)
1
Q
Name the 3 phospholipids on the P-face of the lipid bi-layer and their general functions
A
Phosphatidylserine- apoptosis, coagulation
Phosphatidylethanolamine- particularly present in nervous tissue, cell division
Phosphotidylinositol- signaling, membrane trafficking
2
Q
Name the 2 phospholipids found of the E-face of the lipid bilayer of the plasma membrane
A
Phosphatidylcholine- signaling
Sphingomyelin- myelin sheath
3
Q
What is the name of the coating formed when polysaccharides extend from integral proteins of the plasma membrane?
A
Glycocalyx
4
Q
Describe the anatomy of a lipid raft
A
Micro domain in the plasma membrane: group of integral (and peripheral?) proteins surrounded by a high concentration of glycosphingolipids and cholesterol
5
Q
Describe the difference between COP-II and COP-I
A
COP-II coats vesicles carrying proteins from the RER to the Golgi apparatus where they are modified then carried in vesicles from the trans-golgi network to the plasma membrane
COP-I vesicles carry stuff retrograde from the Golgi apparatus back to the RER
6
Q
Constitutive pathway
A
Proteins leave the cell immediately after synthesis in vesicle but with no secretory products
7
Q
Regulated Secretory Pathway
A
Protein secretion that is regulated by hormonal or neural stimuli. The proteins have to be transiently stored in vesicles within the cytoplasm.
8
Q
Describe the two types of phagocytosis (antibody vs non-antibody)
What does it mean that both are actin dependent?
Are they Clathrin dependent?
A
Antibody mediated phagocytosis is for uptake and disposal of biological materials (such as bacteria) to which antibodies attach
Non-antibody uptake still uses receptors on the cell surface but is for non-biological materials (like carbon inhalation)
Actin rearranges itself to the cell surface in order to project the cell membrane around the particle needing to be phagocytosed
No
9
Q
Describe the process of Clarthin dependent endocytosis
A
A cargo protein fuses with a cargo receptor which is then recognized by adaptin. Clarthin recognizes the adaptin and forms a coated pit which is then pinched off by dynamin and taken into the cell. The Clarthin dissociates and the vesicle fuses with an endosome
10
Q
Pinocytosis
A
“Cell drinking”; small invaginations of extracellular fluid and anything that is soluble. These vesicles eventually fuse with lysosomes.
11
Q
Describe the following signaling types: Endocrine Paracrine Synaptic Autocrine Juxtacrine
A
Endocrine- hormones are carried in the blood to their target cells
Paracrine- signaling molecule travels in extracellular fluid to a nearby cell
Synaptic- special type of paracrine; uses neurotransmitters in a synapse
Autocrine- signal molecules bind to receptors on the same cell
Juxtacrine- signaling molecules are bound to their parent cell and interact with an adjacent cell
12
Q
Enzymatic receptor
A
A ligand binds to activate usually a protein kinase which then phosphorylates another enzyme
13
Q
Channel linked receptors
A
Ligand binds to open up a channel that then lets certain ions into the cell
14
Q
G-protein coupled receptor
A
A ligand binds which causes a conformation change of a G-subunit allowing GTP to bind said protein. The G subunit leaves its receptor home to then bind other proteins such as adenyl cyclase or an ion channel which triggers secondary messengers to turn on protein kinase enzymes which phosphorylate other enzymes.
15
Q
Describe the difference between hydrophilic signaling molecules and hydrophobic signaling molecules
A
Hydrophilic- polypeptide hormones and neurotransmitters. Bind to receptors on the CELL SURFACE
Hydrophobic- steroids and thyroid hormones which can pass straight through the lipid bilayer to then bind a receptor on the nucleus (which allows it to pass into the nucleus and bind to DNA)
16
Q
What is spingomyelinase? What can a deficiency in this enzyme cause?
A
Breaks down excess sphingomyelin (myelin sheaths). A deficiency can cause excess sphingomyelin to build up inside lysosomes and causes enlarged cells in the spleen, liver, lungs, bone marrow, and brain. Type A involves an enlarged liver and jaundice in infants. Type B exhibits an enlarged spleen and liver and usually is found in preteens.
17
Q
Describe the mechanism of Multiple Sclerosis
A
Upregulation of certain cytokines from CSF (like tumor necrosis factor alpha) causes overactivation of sphingomyelinase resulting in degradation of sphingomyelin
18
Q
Describe what an acanthocyte looks like. What causes this shape?
A
Spikey cell. Abetalipoproteinemia causes an excess of sphingomyelin on the outer leaflet of red blood cell membranes.
19
Q
Describe Cystic Fibrosis
A
A mutated gene codes for a CFTR protein (which isn’t normal). This protein is a transmembrane chloride channel that doesn’t actually let chloride through. Usually, the negative charge from chloride ions draws Na+ out of the cell allowing H2O to follow thus washing away excess mucus
20
Q
Cystinuria
A
Normally a carrier protein takes cysteine out of the urine. When a mutation is inherited (both parents), recurrent kidney stones can occur.
21
Q
Describe epithelial tissue
A
Protective layer that covers surfaces of the body and lines ducts and tubes that communicate with the exterior. These cells are close together
22
Q
Describe connective tissue
A
Serves to support and strengthen. Cells are spread apart and the tissues are mainly held together by the intercellular matrix
23
Q
Which are more numerous in the CNS, glial cells or neurons? Which has the larger cell body?
A
Glial
Neuron
24
Q
Fixation
A
Small pieces of tissue are placed in solutions of chemicals that cross link proteins and inactivate degradative enzymes
25
How is dehydration accomplished?
After fixation, the section is immersed in increasing concentrations of alcohol
26
Clearing
A section is placed in a liquid miscible with both paraffin and alcohol. The resulting section is transparent
27
Name the three steps that occur after clearing
Infiltration, Embedding, and Trimming
28
Does collagen stain pink or blue in an H&E stain? Cartilage? What does this mean about the two?
Pink. This means that collagen is basic or acidophilic.
Cartilage stains blue which means it is acidic, anionic, or basophilic.
29
Describe the function of the Smooth Endoplasmic Reticulum. What does it synthesize? What is its role in detoxification and metabolism?
The smooth ER does not have ribosomes because its job is to synthesize non-protein substances such as lipids and steroid hormones (in the endocrine cells of the gonads and adrenal cortex). Cytochrome P450 is found in the SER of liver cells and is involved in the detoxification of metabolic waste products, drugs, alcohol, and other organic substances. The outer membrane of SER also contains enzymes that participate in the release of glucose from glycogen in the liver (metabolism)
30
Where is Ca2+ stored in muscle cells?
Smooth ER
31
What can be found in the cytosol/cytoplasm of a cell?
Membranous and non-membranous organelles, enzymes, oxygen, carbon dioxide, low-weight molecular substrates, metabolites, and waste products.
32
What would a cytoplasm that stains intensely with hematoxylin indicate?
The presence of active protein synthesis (high concentration of basophilic ribosomes)
33
Which types of proteins are synthesized by cytosolic ribosomes? Which are synthesized by ER bound ribosomes?
Intracellular proteins: cytosolic, mitochondria, peroxisomes, nucleus
Extracellular proteins: go first to Golgi apparatus, then are secreted in vesicles, incorporated into the membrane, or go to lysosomes
34
How does the SER work to detoxify the body?
The SER of liver cells has enzymes that work with cytochrome P450 to turn toxic agents into water soluble molecules that can be excreted
35
What types of organelles will be in large concentration in a cell that secretes steroids? What about pancreatic cells?
Smooth ER because it makes lipids and steroids
RER and Golgi because pancreatic cells are secretory cells
36
Describe sickle cell anemia
A point mutation in which valine replaces glutamine in the B chain of hemoglobin. The result is a blood cell that looks like a sickle
37
What happens if an amino acid mutation renders the RER unable to export a1-antitrypsin (A1AT)?
Emphysema
38
Chemiosmotic Coupling
Movement of protons down the concentration gradient(/electrical gradient) back into the mitochondrial matrix
39
ATP/ADP exchange protein and the Voltage Dependent Anion Channel
Exchanges ADP and ATP across inner membrane
Exchanges ADP and ATP across outer membrane
40
What is MERRF? What is the mechanism?
Myoclonic epilepsy with ragged red fibers. It affects muscle cells. A mutation of mitochondrial DNA that codes for the tRNA of lysine causes malformation of two ETC complexes.
41
What happens to denatured or misfolded proteins within the cell?
They conjugate with ubiquinone and are destroyed by proteosomes
42
What does it mean that secretory cells are polarized?
The cell has different structures in different parts. For example, a pancreatic acinar cell has RER on the basilar end and secretory vesicles on the apical end that go out towards the lumen of the gland
43
Cells with great phagocytic activity (macrophages, neutrophils) are rich in which type of organelle?
Lysosomes
44
Heterolysosome
A lysosome that is actively digesting stuff. The broken down nutrients get released back into the cell
45
ATPase
Enzyme found in proteosomes that denatures proteins bound to ubiquitin
46
What is the role of the mitochondria in apoptosis?
The mitochondria releases cytochrome c into the cytoplasm which triggers certain proteases to initiate apoptosis
47
What happens to the mitochondria when a cell undergoes mitosis?
Each new daughter cell gets half a mitochondria
48
Which types of cells might have a large amount of peroxisomes?
Liver and kidney cells (for breaking down harmful ingested substances)
49
What is the mechanism of peroxisomal digestion?
Oxidases make hydrogen peroxide out of a substrate and proteases (like catalase) immediately break it down
50
Where do lysosomes originate from? What about peroxisomes?
Lysosomes originate from the Golgi appartus. Peroxisomes originate from the ER and other peroxisomes
51
Where do lipid and glycogen metabolic enzymes come from?
Smooth ER
52
Tay Sachs disease
Lysosomal storage disorder (LSD) in which hexoaminidase A is deficient causing build up of GM-2 gangliosides in neurons (the result is a vegetative state)
53
Zellweger syndrome
Peroxisomal disorder where the proper enzymes for B oxidation cannot be incorporated because the target signal receptor (in the peroxisome) is absent. The result is lack of plasmalogen production which is the most abundant phospholipid in myelin. Nervous system is affected and it is fatal
54
What are inclusions?
Cytoplasmic structures or deposits that store macromolecules usually not bound by a membrane (lipid droplets form a single layer phospholipid membrane)
55
Cells with high metabolic activity are rich in which type of inclusion molecules?
Glycogen granules
56
What is lipofuscin? What does it look like? How is it different from melanin?
Lipofuscin appears as yellowish brown pigments and accumulates in long-lived cells (cardiac cells, neurons). They are membrane bound remnants of lysosomal byproducts that were not digestible. Melanin is a type of pigment deposit manufactured by melanocytes and pigment cells. It has a protective function.
57
Hemosiderin
Type of pigment deposit; iron-storage complex thought to be the remnants of degraded hemoglobin when an erythrocyte has been phagocytosed such as in the spleen to by a macrophage in the lungs. It appears brown in light microscopy just like lipofuscin
58
True or false: centrioles replicate during cell division
True
59
What is an Axoneme?
Makes of cilia and flagella. 9 microtubule doublets form a circle around a pair of 2 central microtubules. Dynein arms projects from one doublet to the adjacent doublet. The rhythmic grab and release of dynein arms causes motion
60
Tubulin is the building protein for which type of cell filament?
Microtubules
61
What is the main role of intermediate filaments?
Provide mechanical strength and resist shear stress (in epithelial cells, the intermediate filaments extend between cytoplasms of adjacent cells for increased rigidity)
62
Name the location of intermediate filaments composed of the following polypeptides: lamins A, B, & C, vimentin, desmin, glial fibrillary acidic protein, peripherin. What about type I keratins (acidic) or type II keratins (basic)? Neurofilament proteins?
Nuclear lamina (inner lining of nuclear envelope), many cells of mesenchymal origin, muscles cells, glial cells (astrocytes and Schwann cells), some neurons
Both types found in epithelial cells and their derivatives (hair and nails, etc.)
Neurons; axonal intermediate filaments
63
Which of the three cytoskeletal fibers are polar?
Microtubules and microfilaments (actin). Intermediate filaments are not
64
Compare and contrast the location, general structure, and function of the three types of cytoskeletal fibers.
Microtubules- radiating from centrosomes and in axonemes. One microtubule made of 13 protofilaments (made of tubulin which is an a & b dimer). Help maintain cell shape and polarity. Provide tracks for organelle movement. Move cilia and flagella
Microfilaments- made of a helical strand of two F-actin filaments (made of G-actin subunits). Concentrated beneath the cell membrane (inner surface) and in microvilli. Help change the shape of the cell membrane and link epithelial cells together. Help move cells.
Intermediate filaments- antiparallel tetramers of two rod like dimers. Found webbed throughout the cell especially at desmosomes and inside the nuclear envelope. Help maintain cell shape and hold desmosomes together.
65
Which tubulin subunit is the (+) end and which is the (-) end?
B is (+) and a is (-)
66
Dyneins and Kinesins are classified as which type of macromolecule? What is their driving force?
Which goes from + to -?
Molecular motor proteins. ATP driven.
Dyneins go from + to - and Kinesins go from - to +
67
What is a centriole? What is a centrosome? What happens during mitosis?
Centriole is a set of nine microtubule triplets (27 total). A centrosome is two perpendicular centrioles (usually near the nucleus). Before mitosis, the centrosome duplicates and the two move to opposite ends of the dividing cell
68
Where are primary cilia found?
On virtually every cell. They have a 9+0 arrangement with no dyneins and don’t do any motion
69
What is the role of protein bridges in axonemes?
They hold the A tubule to the adjacent B tubule and restrict the movement caused by dyneins (which actually produces the back and forth motion)
70
What are filamin, spectrin, fimbrin, and fascin?
Filamin and spectrin are microfilament linking proteins that help arrange actin into a stiff, cross-linked meshwork that lines the plasma membrane of cells and resists sudden forces (spectrin is known in erythrocytes). Fimbrin and fascin are actin-binding proteins found in microvilli extensions.
71
What is the aggresomal response?
That’s when intermediate filaments aggregate around damaged cell components. After the components have been eliminated, the meshwork re-expands
72
Kartagener’s syndrome
Defects in microtubules and microtubule proteins which can affect the respiratory system and the reproductive system
73
What do colchicine, vinblastine, and vincristine have in common?
They all stop the microtubule function (polymerization or mytotic spindle formation) to arrest inappropriate cell functioning.
74
What is the difference between how cytochalasin B/cytochalasin D and phalloidin impair the proper functioning of actin filaments within a cell?
The first two stop the polymerization of actin while the latter stops the depolymerization
75
How is Alzheimer’s disease related to intermediate filaments?
Neurofilaments in brain tissue can cause neurofibrillary tangles
76
What are Mallory bodies?
Inclusions of intermediate filaments components made of keratin. Happens in hepatocytes due to alcohol liver cirrhosis.
77
What are importins and exportins?
These are target proteins containing nuclear localizing signals that help certain macromolecules into and out of the nucleus
78
3 main components of the nucleolus
Nucleolar organizer DNA (codes for rRNA), pars fibrosa (transcripts of the DNA), pars granulosa (representing mature ribosomes)
79
What happens in the G1 phase?
The cell is accumulating enzymes and nucleotides required for DNA synthesis
80
What is the cell cycle?
G1, S, G2, M
81
Describe the 3 checkpoints of the cell cycle
G1/S checkpoint- is the cell healthy and big enough for DNA synthesis? Is all DNA intact?
G2/M checkpoint- is DNA completely replicated?
Metaphase/Anaphase checkpoint- is all DNA intact? Are microtubules secured to all centromeres?
82
What are the proteins that progress the cell cycle?
Cyclins and cyclin dependent kinases
83
Static cell populations
Describes a mitotic state of somatic cells that no longer divide. CNS cells, cardiac and skeletal muscle cells
84
Stable cell populations
Cells that divide slowly and episodically to maintain normal tissue or organ structure. May be stimulated by injury. Periosteal and perichondrial (bones and cartilage), smooth muscle cells, endothelial cells of blood vessels, fibroblasts of connective tissue
85
Renewing cell populations
Undergoing active mitosis; most likely stem cells
86
Slowly renewing cell populations
Most smooth muscle cells of hollow organs, fibroblasts of uterus, epithelial cells of the lens of the eye
87
Rapidly renewing cell populations
Blood cells, epithelial and dermal cells of the skin, and epithelial cells of the mucosal lining of the alimentary tract
88
Autophagosomes are usually composed of which type of membrane?
Smooth ER
89
Paraptosis
Cell death induced by growth factor receptors; mediating protein is mitogen-activated-protein-kinases (MAPKs). Multiple large vacuoles appear and mitochondria swell
90
Pyroptosis
Cell death stimulated by infectious microorganisms; Capsase-1 enzyme is the protein in question
91
What is the most prominent sign/signal of Huntington’s disease or a similar neurodegenerative disease (think nucleus)
Inclusions of abnormal proteins within the nucleus
92
What is Histone Acetyltransferase (HAT)?
The enzyme that transfers acetyl groups to histone proteins to decondense DNA
93
What are HDACs?
Histone Deaceteylases. They take acetyl groups off of DNA which silences genes and makes DNA less susceptible to DNAse
94
Rett Syndrome
An inactivating mutation of the MECP2 gene results in lack of methylated DNA protein that recruits HDACs to ultimately condense cells and turn OFF gene expression. The OVER EXPRESSION is what causes the neurodegenerative symptoms
95
Metastatic chromosomes are more or less condensed than euchromatin and heterochromatin?
More condensed
96
What is aneuploidy? What are the three types of aneuploidy? Which types are lethal?
When one or more individual chromosomes are missing (or an extra is present);
Nullisomy (both homologs missing); monosomy (only one homolog present); trisomy (three homologs present)
Nullisomy is embryonically lethal; monosomy of autosomes is lethal (Turner syndrome is monosomy of sex chromosomes)
97
What are the apparent and non-apparent symptoms of Turner Syndrome?
Apparent- edema (puffiness) of hands and feet and webbing of the neck
Non-apparent- cardiovascular problems, slow growth, and underdeveloped sexual development
Treatment is usually hormone therapy
98
Which trisomies are lethal and which are not? What are the symptoms?
Trisomies of sex chromosomes have few symptoms and life-span is normal. Trisomy of an autosome is usually lethal (especially Trisomy 16). Trisomy 13 (Patau syndrome) and Trisomy 18 (Edwards syndrome) result in cleft palate, clenched hands, microcephaly, and micrognathia (underdeveloped jaw). Trisomy 21 is known as Down Syndrome and is less fatal than other autosomal trisomies (probably because chromosome 21 is the smallest autosome)
99
Describe Wolf-Hirschhorn syndrome
Del (4) p(15.3). “Greek helmet syndrome”
100
Cri-du-chat syndrome
Terminal deletion: 46, XY, del (5) (p14.2)
101
Robertsonian Translocation
Specific class of translocation in which two acrocentric chromosomes (13, 14, 15, 21, 22) join at the centromere. It does not affect the carrier because all the genetic material is there but it will affect the gametes produced by that carrier
102
What 3 body surfaces are not covered by epithelium?
Articular cartilage, enamel of the tooth, and anterior portion of the iris
103
What two layers make up the basement membrane?
Basal lamina and reticular lamina (beneath)
104
Where can simple squamous epithelium be found?
Lining blood vessels (endothelium), lining of body cavities (mesothelium), lining of respiratory cavities (alveoli), Bowman’s capsule of the kidney
105
Where can simple cuboidal cells be found? What is their function?
Small ducts of exocrine glands, surface of ovary, kidney tubules, thyroid follicles. Absorption, secretion, and protection.
106
Where are simple columnar epithelial cells found? What is their function?
Lining of gastrointestinal tract, lining of gallbladder, some large ducts. Absorption and secretion, protection, lubrication
107
Where are stratified squamous cells found?
Lining of oral cavity, esophagus, vagina. The “wear and tear” areas
108
Where are stratified cuboidal cells found?
Sweat glands and ducts, larger ducts of exocrine glands
109
Where are stratified columnar cells found?
Largest ducts of exocrine glands
110
Where are pseudostratified epithelial cells found? Do they all touch the basement membrane?
Lining of the trachea, bronchi, nasal cavity, ductus deferents, parts of the epididymis. Yes.
111
Transitional Epithelium
Special type of stratified epithelium found exclusively in the renal system. The top layer of cells can stretch and become squamous to accommodate filling
112
Where are stratified squamous keratinized cells found? What happens to their nuclei?
Epidermis. They lose it. Main role is to be water tight
113
Endothelium vs mesothelium
Endothelium lines blood vessels while mesothelium lines body cavities (the pleura and peritoneum are made of mesothelium)
114
What do goblet cells do?
Secrete mucus to cover the epithelial lining of columnar cells
115
What is the brush border made of?
Microvilli and glycocalyx
116
Which type of filament extends into microvilli?
Microfilaments (actin) that are continuous with the matrix within the cell
117
Occludins, claudins, and ZO proteins
Transmembrane link proteins of tight junctions on epithelial cells
118
E-cadherin, catenin complexes
Transmembrane link proteins of belt desmosome (zonula adherens)
119
Integrins
Transmembrane link protein of hemidesmosomes
120
Connexins
Transmembrane link protein of gap junctions between epithelial cells
121
Cadherin family proteins
Transmembrane link proteins of desmosomes
122
What are the two main proteins found in the basal lamina? What about the reticular lamina?
Type IV collagen and laminins. Type III collagen.
123
What’s the difference between microvilli and cilia? Where are these differences found?
Microvilli do not move. They are projections whose purpose is to increase surface area for absorption. Cilia move and are composed of microtubules. Their job is to move stuff through a specific area.
Microvilli in the intestine and cilia in the trachea
124
What is the difference between thick and thin skin?
In thick skin, the keratinized layer is thicker than the cellular layer. In thin skin, it is thinner
125
What types of glycosylated features of the cell are stained pink or magenta by a PAS agent?
Mucin of goblet cells, basement membrane, brush borders, cartilage, collagen
126
What type of collagen anchors the hemidesmosomes to the basal lamina?
Type VII
127
What are basal interdigitations? What are found in the alcoves? What types of cells?
Infoldings of the basal membrane to create alcoves within the cytoplasm. Mitochondria found in the alcoves. Extra surface area makes it easier to generate an extracellular osmotic gradient. Found in epithelial cells of renal system, ducts of sweat glands, and ciliary process of the eye
128
Why is the basal membrane PAS positive?
Cause the two layers are made up of glycoproteins!
129
How are fibroblasts related to the reticular lamina?
Fibroblasts make the stuff that makes up the reticular lamina
130
Serous vs mucous gland. Give examples of each type and examples of seromucous glands
Serous is proteins packaged into secretory granules. Found in parotid glands, pancreas exocrine glands, and uterine glands. Mucus is polysaccharides added to protein substrates. Also packaged into secretory granules. Found in goblet cells of GI and respiratory tract. Some salivary glands and part of genital tract. Seromucous glands are most of the glands learned in the head and neck block.
131
Acinar vs tubular gland
```
Acinar= flask shaped
Tubular= tube shaped
```
132
What is the difference between merocrine, apocrine, and holocrine secretions?
Merocrine are normal exocytosis (salivary glands, exocrine portion of pancreas); apocrine release a piece of the cell membrane with it (mammary glands- lipid portion); holocrine is the entire cell being released as part of the secretion (sperm)
133
Sites of origin for DNA replication are rich in which nucleotides?
Adenine and Thymine (only 2 H bonds between the two)
134
What does single strand DNA binding protein do?
Ensures the single strand DNA does not re-anneal during replication
135
Ciprofloxacin
Bacterial topoisomerase inhibitor (antibiotic)
136
Irinotecan and Topotecan
Type I topoisomerase inhibitors used in treating colorectal and ovarian cancer
137
Doxorubicin, etoposide, ellipticine
Type II topoisomerase inhibitors for treating cancer
138
Difference between exonuclease activity of bacteria and eukaryotes (Okazaki fragments; RNA primer replacement)
Bacteria uses DNA polymerase I to replace the RNA bases. Eukaryotes don’t have a polymerase with exonuclease activity, so a complex containing FEN-1 and RNAse H has to be used
139
What types of cells have high telomerase activity?
Telomerase helps protect the ends of chromosomes being replicated. Post-mitotic cells have low telomerase activity while mitotic cells such as skin cells or cancer cells will have high telomerase activity
140
What is Highly Active Anti-Retroviral Therapy (HAART)?
Using analogs like AZT (thymine analog) or DDI (purine analog) for which reverse transcriptase has high affinity. They don’t have open 3’ OH groups to which DNA can attach
141
Acyclovir and Gancyclovir
Both guanosine analogs that get phosphorylated by viral proteins then incorporated into viral DNA and subsequently stop replication. Used against herpes simplex (HSV), varicella zoster (chickenpox), and herpes zoster (shingles). Gancyclovir used against cytomegalovirus.
142
Give an example of Base Excision Repair
Methylcytosine gets deaminated to become thymine. BER recognizes the T-G base pairing and replaces the T with cytosine
143
How does nucleotide excision repair work?
Say you have a thymine dimer (more problematic than a simple BP misplacement). XP-C or Rad23B recognizes this problem and recruits Helicase to unwind the DNA. Two endonucleases (XP-F and XP-G) cut out a section that then gets replaced by DNA polymerase
144
Cisplatin can be used to stop cancerous cells through apoptosis unless..
The cells have the ERCC1 gene that codes for XP-F (because this will go through and fix the messed up DNA).
145
Hereditary colorectal cancer patients are usually missing which protein? What does it do?
MLH1 or MSH2 which are both involved in mismatch excision repair
146
Patients with Xeroderma Pigmentosum cannot repair UV damaged DNA because of mutated genes coding for which portion of the NER pathway?
Recognition (XP-C), Helicase activity (TFIIH), or endonuclease activity (XP-F, XP-G)
147
Which two genes are commonly mutated in patients with Cockayne syndrome? What is their function?
ERCC8 and ERCC6. Both have helicase activity but the result is that the NER complex cannot scan for stalled transcription machinery. The result is premature aging and neurodegeneration.
148
Epidermolysis bullosa
Faulty genes encoding lamanin-5 chains. These normally link integrin and hemidesmosomes to the basement membrane. Blistering can easily occur
149
Adenocarcinoma
Cancer cells arising from glandular epithelium
150
Pemphigus and pemphigoid
Body produces abnormal antibodies against desmoglein 1&3 and linking proteins in hemidesmosomes respectively. Blistering can easily occur
151
MLH1 and MLH2
Proteins that help recognizing mispairings in DNA replication (pair of mismatch repair mechanism)
152
Highlight some of the differences between eukaryotic and prokaryotic promoter regions
Prokaryotes have a TATAAT box -10 BPs from the +1 start site. They can also have an operator within that promoter where activators or repressors bind. Eukaryotes can have a lot larger promoter region and more binding sites. At -30 is the TATA box where the TATA binding protein binds allowing the formation of the PIC (preinitiation complex). At -10 is the Inr sequence where DNA unwinds for transcription and it usually contains the +1 base pair. Other sequences can be upstream or downstream of the gene (or within it).
153
What are the 5 key proteins involved in NER?
XP-C and/or Rad23B detect the error (usually a thymine dimer), TFIIH is recruited for helicase activity, and XP-F and XP-G remove a patch surrounding the lesion
154
What is the mechanism of the Wilm’s Tumor? What are the symptoms?
The Wilm’s Tumor Gene codes for a repressor that binds the promoter region of certain protooncogenes (specifically amphiregulin, BCL-2 anti-apoptosis). If the gene is mutated, the oncogenes go to town. It presents as a painless mass in the kidneys
155
Which mutation is critical in the malformation of the Pit-1 protein (causes short stature and small bones)
B174G mutation. Required for proper binding to the Growth Hormone promoter region.
156
Describe the functions of RNA polymerase II, TFIIB, and TFIIH
Pol II catalyzes RNA synthesis. TFIIB recruits TFIIH and also has helicase activity. TFIIH has helicase activity and phosphorylates the serine residues of the CTD of Pol II (initiating it)
157
How does HIV prevent premature RNA termination?
At its 5’ end, the viral transcript binds viral TAT and host Cyclin T which activates host CDK9 which is a kinase that hyperphosphorylates RNA pol II
158
What is the Cap synthesizing complex and where is it located? When does it perform its function?
Cap synthesizing complex is attached to the CTD of RNA Pol II and it “caps” (methylates) the 5’ end of the hnRNA with 7-methyl-guanosine while transcription is still occurring.
159
Why are the 5’ cap and poly A tail so important? What enzyme cleaves the RNA transcript and where? Which enzyme adds the poly A tail?
The 5’ cap and poly A tail “mature” the RNA and help it leave the nucleus. Both stabilize the RNA. RNA pol II cleaves the transcript AFTER the poly A signal sequence AND poly A region (where the tail will be added). Poly A polymerase 3 adds the tail
160
What is a 3’ UTR?
3’ “untranslated region”. The 3’ UTR is always a stop codon
161
What are the sequences that define an intron?
GT/GU is the start of the intron and AG is the end of the intron (the exons start outside of those borders)
162
What is B-Thalassemia and what does it have to do with splicing? What is the difference between B^0 thalassemia and B+ thalassemia?
A thalassemia is any sort of mutation that affects either of the subunits that make up hemoglobin making it less effective at carrying oxygen. B thalassemia affects the B subunit. A mutation in the splice donor or splice acceptor site can cause absence of B-globin (B^0) or reduced expression of it (B+)
163
What causes Dystrophia Myotonia? What are the symptoms? (DMPK)
The Dystrophia Myotonia Protein Kinase (DMPK) usually has CTG (CUG) repeats but an autosomal dominant mutation can cause someone to have a much larger number of repeats. This makes it harder for the mRNA to leave the nucleus. Muscleblind protein which usually binds CUG-BP binds the CUG repeats on the mRNA. The increase in CUG-BP causes abnormal splicing events in other mRNA. This results in cardiac abnormalities, insulin resistance, and myotonia
164
What is ichthyosis? What causes it?
Scaly dry skin. When filaggrin mutations occur, there is no water tight barrier to retain moisture and the skin dries out.
165
Vitiligo
Skin depigmentation
166
What are the unencapsulated nerves/receptors within the dermis?
Merkel cells and associated unencapsulated nerve end, free nerve endings (sense pain, heat, noxious stimuli, etc.), root hair plexuses
167
The glassy membrane of a hair follicle is continuous with which tissue layer?
Basement membrane of the epidermis
168
The internal and external root sheaths are continuous with which cellular layer?
Stratified epidermis
169
Which hair follicle layer is considered “sheath-like”? Which follicular layer is vascularized?
The cuticle
The dermal papilla
170
Where are there no sebaceous glands in the skin?
Palms and soles
171
Name the three cell types of an eccrine sweat gland
Pyramidal dark cells- secrete EOSINOPHILIC bactericidal peptidases
Myoepithelial cells- contract to push sweat through lumen
Clear cells- produce sweat by transporting fluid from interstitial fluid into lumen
172
What do eccrine ducts reabsorb?
Na+
173
The glands of apocrine sweat glands are lined with which type of cell? What type of secretion do they exhibit?
Simple cuboidal. Merocrine (they are misnamed)
174
What is a Kozak sequence? What does it contain?
The sequence that indicates where the ribosome binds to start translation. Contains AUG codon.
175
How many types of methionine aminoacyl-tRNA molecules are there?
2
176
What are eIFs? Which ones are important in translation initiation?
Eukaryotic Initiation Factors. eIF3 binds to the 40S subunit of the ribosome first and keeps it separate from the 60S subunit. eIF2 mediates binding of the initiation methionine tRNA to the 40S subunit. This is called the preinitiation complex.
eIF4A has helicase activity to break down the secondary structure of the mRNA and eIF4B scans for the start codon AUG
177
Describe Leukoencephalopathy, CNS Hypomyelination, and Vanishing White Matter (VWM)
Fever which causes degradation of glial cells within the CNS (which provide myelination to neurons). Appears as degrading white matter on CT scan. Severity is inversely correlated with age.
Caused by a missense mutation in the gene encoding eIF2. This creates 2 problems: 1) translation is effected because the preinitiation complex doesn’t form properly, and 2) eIF2 normally stalls translation when someone has a fever otherwise proteins become misfolded. Glial cells are highly susceptible to these problems.
178
What molecule powers the reactions involving eIFs, eEFs, and translocation?
GTP hydrolysis
179
What are the respective effects of tetracycline, streptomycin, chloramphenicol, erythromycin, and rifamycin on translation elongation (all antibiotics)?
Tetracycline blocks the binding of aminoacyl-tRNA to the A-site. Streptomycin prevents the transition from the initiation complex to the elongation complex. Erythromycin prevents translocation of the ribosome 80S unit. Chloramphenicol prevents the peptidyl transferase reaction (formation of the peptide bond). Rifamycin binds RNA polymerase to prevent transcription.
180
Describe the three main functions of molecular chaperones
As elongation occurs, chaperones bind the polypeptide to prevent premature hydrophobic interactions that are not supposed to occur (later ones might be between different amino acids). Chaperones help with refolding after heat stress. Chaperones keep the protein unfolded so it can pass through a membrane (like the RER).
181
Peptidyl Prolyl cis-trans isomerase? Protein Disulfide Isomerase?
Changes trans prolines to cis prolines (better for hairpin turns)
Breaks inappropriate disulfide bonds until the correct ones can be made
182
Describe a mechanism of Alzheimer’s that involves amyloidosis.
Amyloid Precursor Protein is usually a-helical, but proteolytic cleavage can cause misfolding into B-sheets. The hydrophobic regions of these B sheets cause aggregation which creates an insoluble molecule known as an Amyloid Plaque. They aggregate in the extracellular space and cause neuronal cell death
183
For the following diseases, name the protein that is misfolded, the amyloid that is formed, and the consequence of such aggregations: Alzheimer’s, Type II diabetes, Prion disease, Huntington’s disease, Parkinson’s, Amyotrophic Lateral Sclerosis, Spinal cerebral ataxia
Alzheimer’s- Amyloid Precursor Protein, B amyloid plaques, neuronal cell death
Type II- Amylin (insulin), apoptosis of B islet cells
Prion- PrPc, PrPsc, neuronal cell death
Huntington’s- Huntingtin protein, mHTT (if trinucleotide repeats > 40), interferes with neurotransmitter release, neuronal cell death.
Parkinson’s- a-synuclein, Lewy bodies, death of dopaminergic neurons
ALS- superoxide dimutase protein (SOD), dementia/neuronal apathy
SCA- Ataxin, trinucleotide repeats coding polyQ, neuronal cell death
