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MOD Exam I > Robbins Ch 1- The Cell > Flashcards

Robbins Ch 1- The Cell Flashcards

1
Q

what percentage of the genome is comprised of protein-encoding genes?

A

1.5%

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2
Q

The banding pattern as seen in chromatids are attributed to what contents, and where do genes usually localize?

A

GC with less GC content in bands relative to interbands. Genes usually localize to interband regions.

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3
Q

The _ are noncoding regions of DNA that initiate gene transcription.

A

Promoter region, usually located upstream of of their associated gene.

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4
Q

_ are regulatory elements that can modulate gene expression over distances of 100kB or more by looping back onto promoters and recruiting additional factors that are needed to drive expression of pre-mRNA spaces.

A

Enhancers

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5
Q

The _ are spliced out of the pre-mRNA to produce the definitive message that is translated into protein

A

Introns

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6
Q

Transposons, noncoding regulatory RNA’s regulatory factor binding regions are all examples of _

A

noncoding elements

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7
Q

In higher organisms, the protein-coding genes are close together or separated by long stretches of DNA?

A

separated by long stretches of DNA

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8
Q

About what percentage of human genome either binds proteins, or assigned some functional activity?

A

80%

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9
Q

What part of the genome (coding or noncoding) that which provide the critical architectural planning?

A

noncoding regionss

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10
Q

What are some examples of non-protien-coding sequences found in the human genome?

A
  • promoter and enhancer (provide binding sites for TF
  • Binding site for factors that organize and maintain higher order chromatin structures
  • noncoding regulatory RNAs (eg. miRNA, IncRNA)
  • Mobile genetic elements (e.g. transposon)
  • telomeres
  • centromeres
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11
Q

what is polymorphism?

A

genetic variations

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12
Q

It’s said that any two individuals are 99.5% identical. what are the two most common forms of DNA variation in the human genome?

A
  1. single-nucleotide polymorphisms (SNPs)

2 copy-number variations (CNV)

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13
Q

Where are SNP’s found?

A

They occur across the genome - within exons, introns, intergenic regions, and coding regions. In coding regions it’s only about 1%.

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14
Q

SNP’s located on _ can alter gene expression where SNP may have direct influence on disease susceptibility.

A

Non-coding regions like regulatory elements.

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15
Q

Explain what it means by SNP and the causative genetic factor are in linkage disequilibrium.

A

It’s the idea that neutral SNP’s happen to be co-inherited with a disease-associated gene as a result of physical proximity.

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16
Q

what’s responsible for a large portion of human phenotypic diversity, SNP or CNV?

A

CNV

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17
Q

what is epigenetics?

A

Heritable changes in gene expression that are not caused by alterations in DNA sequences.

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18
Q

what are nucleosomes?

A

DNA segments about 147 BP long that are wrapped around a central core structure of highly conserved low molecular eight proteins called histones.

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19
Q

The DNA-histone complex resembles a series of beads on a string joined by short DNA linkers, this is commonly known as_

A

chromatin.

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20
Q

What is heterochromatin?

A

cytochemically dense and transcriptionally inactive DNA.

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21
Q

what is euchromatin?

A

cytochemically dispersed and transcriptionally active DNA

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22
Q

what effects do chromatin remodeling complexes have on histones and on DNA?

A

Chromatin remodeling complex can reposition nucleosomes (which are wrapped around histones) on DNA, exposing or obscuring gene regulatory elements such as promoters.

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23
Q

What do chromatin write complexes do?

A

carry out more than 70 different histone modifications generically denoted as marks, these include methylation, acetylation, and phosphorylation.

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24
Q

During histone methylation, what two amino acids are commonly methylated by specific write enzymes?

A

Lysine and arginine

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25
Q

During histone acetylation, _ residues are acetylated by histone acetyl transferase whose modification tend to what do?

A

lysine.

open up the chromatin and increase transcription.

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26
Q

What is the role of histone deacetylase (HDAC)?

A

reverses histone acetylation and thus leads to chromatin condensation.

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27
Q

What aa is commonly phosphorylated in histone and what effect does it have?

A

Serine. depending on the specific residue, ti can open DNA for transcription or condense it.

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28
Q

What effect doe DNA methylation have on transcription?

A

inhibits transcription

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29
Q

What role do chromatin organizing factors play?

A

bind to noncoding regions and control long-range looping of DNA.

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30
Q

what is the function of miRNA?

A

Posttranscriptional silencing of gene expression

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31
Q

Explain the process of gene silencing by miRNA work.

A

Transcription of miRNA gene produces a primary miRNA, which is progressively processed through various steps including trimming by DICER and forms a double stranded miRNA. The miRNA then unwinds and the resulting single strands are incorporated into the multiprotein RNA-induced silencing complex (RISC). Subsequent base pairing between the miRNA stand and its target mRNA directs the RISC to either induce mRNA cleavage or repress its translation.

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32
Q

what is the significance of seed sequence in mRNAs?

A

it’s located in 3’untranslated region (UTR) that determines the specificity of miRNA binding and gene silencing.

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33
Q

how do IncRNAs modulate gene expression?

A

They can bind to regions of chromatin, restricting RNA polymerase access to coding genes within region thus inhibiting transcription. It was also found that many enhancers are sites of IncRNA synthesis and thus IncRNA appears to often increase transcription from gene promoters.

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34
Q

The physiologic X chromosome inactivation as done by XIST is an example of what type of noncoding RNA?

A

long noncoding RNA

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35
Q

new proteins that are destined for the plasma membrane or beyond are produced in _ and are assembled in _ .

A

Produced in RER and assembled in Golgi

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36
Q

where are proteins destined for the cytosol produced?

A

On free ribosomes.

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37
Q

On what tissue types are you like to find cells with abundant SER?

A

gonads, liver and etc where it is used for steroid hormone and lipoprotein synthesis.

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38
Q

Lysosomes are intracellular organelles that contain degradative enzymes that permit the digestion of _

A

macromolecules like proteins, polysaccharide, lipids, and nucleic acids.

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39
Q

What role does peroxisomes play?

A

Breakdown of fatty acids, generating hydrogen peroxide in the process.

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40
Q

what role does mitochondria play?

A
  • oxidative phosphorylation
  • source of metabolic intermediates that are needed for anabolic metabolism
  • site of synthesis of certain macromolecules like heme
  • contain sensors of cell damage that can initiate apoptosis.
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41
Q

The bilayer of plasmambrane is composed of heterogenous collection of different phospholipids which are distributed asymmetrically. what are some examples of these asymmetric partitioning of phospholipids and what are their importance?

A
  1. Phosphatidylinositol - on INNER leaflet. It can be phosphorylated and serve as an electrostatic scaffold for intracellular proteins; alternatively, polyphosphoinositides can be hydrolyzed by phospholipase C to make IC 2nd signals like DAG and IP3
  2. Phosphatdylserine - normally on inner face and confers a negative charge involved in electostatic protein interaction. when this is flipped, it’s a death signal
    3 Glycolipids and sphingomyelin - on the extracellular face. Glycolipid (negatively charged) important in cell-cell interaction and cell matrix interactions, like inflammatory cell recruitment and sperm-egg interactions
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42
Q

What are the functions of the proteins and glycoproteins that are studded on the plasma membrane?

A

1 ion and metabolite transport
2 fluid-phase and receptor mediated uptake of macromolecules
3 cell-ligand, cell -matrix, and cell-cell interactions

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43
Q

Integral membrane proteins have an positive and a negative ends. Where does the positive end lie?

A

In the cytoplasmic side which anchor the proteins to the negatively charged head groups of membrane phospholipids

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44
Q

The extracellular face of the PM is diffusely studded with carbohydrates. What is the function of the glycocalyx?

A

Functions as a chemical and mechanical barrier, and is also involved in cell-cell and cell-matrix interactions

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45
Q

Channel proteins permit rapid movement of solutes that are restricted by size and charge by creating _ .

A

hydrophilic pores.

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46
Q

How to carrier proteins work to transport?

A

They bind their specific solute and undergo a series of conformational change to transfer the ligand across the membrane; their transport is slow

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47
Q

In passive transport, what two factors play a role to drive solute movement?

A

concentration and/or electrical gradient between the inside and outside of cell.

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48
Q

What kind of proteins (carrier, channels or both) are used in active transport?

A

Carrier proteins ONLY.

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49
Q

What are multidrug resistance (MDR) proteins and what is their significance in cancer therapy?

A

They pump polar compounds out of the cells. These proteins render cancer cells resistant to treatment by pumping the chemotherapeutic drugs out of the cell.

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50
Q

what are two fundamental ways that endocytosis take place.

A
  1. Small molecules take up by invagination of the plasma membrane called caveolae
  2. Bigger molecules taken up by binding to specific cell-surface receptors; internalization occurs through ta membrane invagination process driven by an intracellular coat of clathrin proteins which spontaneously assemble into a basket like lattice to drive invagination.
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51
Q

what is transcytosis?

A

movement of endocytosed vesicles between the apical and basolateral compartments of cells. this allows transferring of large amounts of intact proteins across epithelial barriers.

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52
Q

_ is a form of endocytosis that which is associated with GPI-linked molecules, cAMP binding proteins, SRC-family kinases and the folate receptor.

A

Caveolae-mediated endocytosis.

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53
Q

What is potocytosis?

A

internalization of caveolae with any bound molecules and associated extracellular fluid

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54
Q

What is the difference between potocytosis (cellular sipping) and pinocytosis (cellular drinking)?

A

Potocytosis is caveolae-mediated where caveolae containing extracellular fluid is internalized. Pinocytosis is receptor-mediated where the plasma membrane invaginates and is pinched off to form a cytoplasmic vesicle.

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55
Q

What kind of uptake mechanism do molecules like transferrin and LDL use?

A

receptor-mediated endocytosis.

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56
Q

What defect is responsible for familial hypercholesterolemia?

A

defects in receptor-mediated transport of LDL

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57
Q

What are actin microfilaments?

A

they are fibrils formed from globular protein actin (G-actin). The G actin polymerize into long filaments (F-actin) that interwine to form double-stranded helices with a defined polarity.

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58
Q

When new globular subunits are added to actin microfilaments on which end are they added?

A

positive end

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59
Q

What is the purpose of actin filaments in non-muscle cells?

A

F-actin assembles via an assortment of actin-binding proteins into well-organized bundles and network that control cell shape and movement.

60
Q

Lamin A, B and C are type of _ 1_filaments that which can be used to identify tumor cell that have originated in 2.

A
  1. Intermediate filaments

2. nuclear lamina of all cells

61
Q

Vimentin can be used to identify cell that have originated from _.

A

mesenchymal cells (fibroblasts, endothelium)

62
Q

Desmin can be use to identify cells that have originated _.

A

muscle cells

63
Q

Neurofilaments are components of _

A

axons of neurons.

64
Q

what is the general role of intermediate filament?

A

impart tensile strength and allow cells to bear mechanical stress.

65
Q

Muscular dystrophy, progeria are examples of diseases that have defects in what?

A

Mutations in lamin which are part of the intermediate filaments.

66
Q

_ are fibrils composed of non-covalently polymerized dimers of alpha and beta tubulin that is constantly elongating or shrinking how tubes with a defined polarity.

A

microtubules

67
Q

The negative end of microtubules are embedded in what?

A

microtubule organizing center (MTOC aka centrosome)

68
Q

what are the three basic types of cell junctions?

A
  1. Occluding junctions (tight junctions)
  2. Anchoring junctions (desmosomes)
  3. Communicating junction (gap junctions)
69
Q

Occluding junctions seal 1 together to create a 2 that restricts 3 movements of ions and molecules.

A
  1. adjacent cells
  2. continuous barrier
  3. paracellular
70
Q

Transmembrane proteins that mediate the cell-cell interaction as seen in occluding junction include_.

A

occludin, claudin, zonulin, and catenin

71
Q

What is the role of desmosomes?

A

mechanically attach cells and their intracellular cytoskeletons to other cells or to the ECM.

72
Q

what is a spot desmosome aka macula adherens?

A

focused adhesion between cells and is small and rivet-like.

73
Q

What is hemidesmosome?

A

Focused attachment of cell to ECM.

74
Q

What is belt desmosomes?

A

Adhesion domains as broad bands between cells.

75
Q

cell-cell desmosomal junctions are formed by homotypic association of transmembrane glycoproteins called _. What are these glycoproteins called in spot desmosome? in belt desosomes?

A

cadherins. In spot desmosomes, these cadherins are called desmogleins and desmocollins. In belt desmosomes theyre called E-cadherins.

76
Q

In hemidesmosomes, the transmembrane connector proteins are _

A

integrins

77
Q

In communicating junctions, there are dense planar array of pores called _ made from transmembrane proteins called _.

A

Connexons made from connexins.

78
Q

The permeability of the communicating junctions is rapidly reduced by _ or _.

A

lowered intracellular pH or increased intracellular Ca++.

79
Q

_ is the site for synthesis of all transmembrane proteins and lipids for plasma membrane and cellular organelles.

A

ER

80
Q

RER functions to _ directed by specific signal sequences on the N-termini of nascent proteins

A

translate mRNA into proteins.

81
Q

For proteins lackign a signal sequence, where does translation of mRNA take place?

A

on free ribosomes in the cytosol.

82
Q

What keeps proteins in the ER until all the proper modifications and conformation are complete?

A

Chaperone molecules

83
Q

In cystic fibrosis, an absence of a single amino acid (Phe) leads to the mutation in CFTR protein. what kind of protein is CFTR and what is the consequence?

A

CFTR is a membrane transporter. The defect in CFTR, leads to misfolding, ER retention, and degraded.

84
Q

What is ER stress response?

A

excess accumulation of misfolded proteins- exceeding the capacity of the ER to edit and degrade them. It leads to unfolded protein response or UPR that triggers cell death through apoptosis

85
Q

Protein modification takes place in golgi progressively as it from _ to _.

A

from cis (near the ER) to trans (near the plasma membrane)

86
Q

N-linked oligosaccharides are added to proteins in what organelle?

A

In the ER and are pruned and further modified in the golgi.

87
Q

Glycosylation of protein that which adds mannose-6-phosphate receptor destines the protein to what?

A

lysosome

88
Q

Acid hydrolases are found in what organelle?

A

lysosomes.

89
Q

what are some examples of acid hydrolase?

A

protease, nuclease, lipase, glycosidase, phosphatase, and sulfatases.

90
Q

In autophagy, senescent organelles or denatured proteins are targeted for lysosome-driven degrdation by encircling them with a double membrane derived from the ER and marked _ proteins.

A

LC3 (microtubule-associated protein 1A/1B light chain 3)

91
Q

Macromolecules destined for catabolism by lysosome get there in what three ways?

A
  1. material internalized by fluid-phase pinocytosis or receptor-mediated endocytosis which goes from early endosome to late endosome which matures into lysosome
  2. autophagy via autophagosome which fuses with lysosome
  3. Phagocytosis which forms phagosome that subsequently fuses with a lysosome.
92
Q

what is the role of proteosome?

A

degrades cytosolic proteins that are marked by ubiquitin

93
Q 
Mitochondrial disorders can be 
A. X-linked
B. autosomal
C. maternally inherited
D. All of the above
E. A and C only
F. C only
A

D. All of the above

94
Q

_ of mitochondria is the site of ATP synthesis.

A

intermembrane space

95
Q

Thermogenin are located in what part of the mitochondria and what is their function?

A

Located in inner membrane and functions to generate heat.

96
Q

What is Warburg effect?

A

It’s the idea that rapidly growing cells upregulate glucose and glutamine uptake and decrease their production of ATP per glucose molecule. Both glucose and glutamine provide carbon moieties that prime the mitochondrial TCA cycle but instead of being used to make ATP, intermediates are spun-off to make lipids and nucleic acids and proteins.

97
Q

Mitochondria regulates balance of cell survival and death via necrosis and apoptosis. In necrosis (external cellular injury) damage to mitochondria induces the formation of _ in the outer membrane.

A

mitochondrial permeability transition pores which allows dissipation of proton potential so that mitochondrial ATP generation fails and cell dies.

98
Q

Mitochondrial damage is a sign of reversible or irreversible injury?

A

irreversible.

99
Q

Both too much apoptosis and failure to of apoptosis can lead to disease. Too much apoptosis can lead to 1 and failure of apoptosis can lead to _2.

A
  1. neurodegenerative disorders

2. malignancy as seen in cancer

100
Q

Signals that most cells respond to can be classified into what general groups?

A
  1. damage to neighboring cells and pathogens via danger signals
  2. Contact with neighboring cells via gap junctions
  3. Contact with ECM via integrins
  4. Secreted molecules like growth factors, hormones, neurotransmitters, cytokines etc.
101
Q

What are some extracellular cell-cell signaling pathways:

A

paracrine signaling
autocrine signaling
synaptic signaling
endocrine signaling

102
Q

As a result of cell-surface receptor binding by a ligand, what are some downstream effects?

A
  1. open ion channels
  2. activate an associated GTP-binding regulatory protein (g-protein)
  3. activate an endogenous or associated enzyme, often a tyrosine kinase
  4. trigger a proteolytic event or change in protein binding or stability that activates a latent transcription factor (Notch, Wnt, hedgehog)
103
Q

Give an example of a receptor associated kinase activity signaling pathway, and a nonreceptor associated with kinase activity signaling pathway.

A

Receptor associated: receptor kinase kinase which responds to ligands like insulin, epidermal growth factor, platelet derived growth factor);
Non-receptor tyrosine kinase: SRC-family kinase. these have no intrinsic catalytic activity, instead a separate intracellular protein, nonreceptor tyrosine kinase- phosphorylates specific motifs on receptor or other proteins.

104
Q

the Wnt protein acts as a ligand for what receptor?

A

Frizzled family receptors.

105
Q

The wnt/Frizzled signaling pathway regulates what?

A

regulate instracellular beta catenin. Normally Beta-catenin is degraded constantly, but when Wnt binds to Frizzled, it recruits dishelved and leads to disruption fo degradatio-targeitng complex. beta-catanin can then go to nucleus to transcribe things.

106
Q

MYC and JUN are transcription factors that is needed for _.

A

regulation and drives gene expression leading of cell growth.

107
Q

_ is a transcription factor that is needed for arrest of cell growth.

A

p53

108
Q

what are some roles of growth factors?

A

-stimulates the activity of genes that are required for cell growth and cell division and it does it by:
1 promote entry of cells into cell cycle
2. relieve blocks on cell cycle progression
3. prevent apoptosis
4. Enhance biosynthesis of cellular components.

109
Q

Aside from stimulation of cell proliferation and survival, what other roles do growth factors play?

A

They drive a host of nongrowth activities like migration, differentiation, and synthetic capacity.

110
Q

Because of growth factors role in cell cycle progression, cell proliferation and survival, many growth factor pathways genes are _

A

proto-oncogenes.

111
Q

EGF and TGF-a are produced by what cells and are mitogenic what cells?

A

produced macrophages, epithelial cells and mitogenic for hepatocytes, fibroblast, and other epithelial cells.

112
Q

EGFR1 is a _ type of receptors that which when mutated can lead to cancers of lung, head&neck, breasts and brain

A

tyrosine kinase

113
Q

ERBB2 receptor mutation is commonly seen in what type of cancer?

A

Breast cancer

114
Q

Heptacytes growth factors are mitogenic for what cells?

A

hepatocytes, and most epithelial

115
Q

What cells produces HGF?

A

fibroblasts, and most mesenchymal cells, endothelium and non-hepatocyte liver cells.

116
Q

_ is the receptor for HGF which has tyrosine kinase activity and when mutated can lead to tumors mainly seen in _ and _.

A

MET.

renal and thryoid papillary carcinomas

117
Q

Which isoform of PDGF are always active?

A

PDGF, AA, AB, and BB

118
Q

PDGF acts by binding to what type of receptor?

A

tyrosine kinase

119
Q

What is the function of TGF-a

A

stimulates proliferation of hepatocytes and other epithelial cells.

120
Q

Which growth factor stimulates endothelial cells and increases vascular permeability

A

VEGF

121
Q

Which growth factor is chemotactic for neutrophils, macrophages, fibroblast, smooth muscles and activates and stimulates proliferation of fibroblasts, endothelial and other cells and stimulate ECM protein synthesis.

A

PDGF

122
Q

Which GF acts to stimulate angiogenesis and ECM protein synthesis?

A

FGF (1 and 2)

123
Q

Which GF is chemotactor for leukocytes and fibroblasts and stimulate ECM protien syntehsis and suppress acute inflammation?

A

TGF-beta

124
Q

VEGF-A plays a major role in _.

A

blood vessel development. VEGF-A is a major angiogenic factor.

125
Q

the most important inducer of VEGF production is via _

A

hypoxia-inducible factor (HIF-1) after hypoxia.

126
Q

_ belongs a family of about 30 members that include BMP, activins, inhibiins, mullerian inhibiting susbtance.

A

TGF-beta

127
Q

TGF-beta reeptors ( types 1 and II) both have 1 kinase activity and induce phosphorylation of a variety of down-stream cytoplasmic TF called 2.

A
  1. serine/threonine

2. Smads

128
Q

What effects do TGF-beta have on matrix metalloproteinase?

A

decrease MMP activity and increase activity of tissue inhibitors of proteinase (TIMPS)

129
Q

what role does ECM play?

A

1 mechanical support

  1. Control of cell proliferation
  2. scaffolding for tissue renewal
  3. establishment of tissue microenvironment.
130
Q

What is the major components of interstitial matrix?

A

Fibrillar and nonfibrillar collagens, fibronectin, elastin, proteoglycans, hyaluronate, and other.

131
Q

what is the major constituents of basement membranes?

A

amorphous nonfibrillar type IV collagen and aminin

132
Q

Listed below are constituents of ECM. For each state its function in ECM.

  1. Fibrous structural proteins (collagen and elastins)
  2. Proteoglycans and hyaluronan
  3. Adhesive glycoproteins
A
  1. Confer tensile strenght and recoil
  2. water-hydrated gell that permit copressive resistance and lubrication
  3. connect ECM elements to one another and to other cells.
133
Q

which collagen types are fibrillar and form linear fibrils stabilized by interchain hydrogen bonding.

A

type I, II, III and V. These types are major proportion of connective tissue in tendons, bones, cartilage, blood vessels, and skin.

134
Q

Explain how vitamin C deficiency leads to skeletal deformities in kids, and weak vascular wall basement membrane and poor healing in adults.i

A

The tensile strength of the fibrillar collagens derives from lateral cross-linking of the triple helices, formed by covalent bonds faciliated by the activity of lysyl oxidase. the formation of this bond is dependent on vitamin C.

135
Q

Genetic diseases like oteogenesis imperfecta and Ehler’s Danlos syndrome are defects in _.

A

collagens

136
Q

What is the role of FACITs in non-fibrillar colllagens?

A

Non-fibrillar collagens like type IV help regulate collagen fibril diameters or collagen-collagen interactions via FACITs

137
Q

Provide a general overview of proteoglycans and hyaluronan are organized.

A

Proteoglycans consist of long polysaccharides called glycosaminoglycans like keratan sulfate and chondroitin sulfate which attach to a core protein and these are then inked to a long-hyaluronic acid and polymers called hyaluronan

138
Q

what are some examples of adhesive glycoproteins as seen in ECM?

A

fibronectin (part of interstitial ECM) and laminin (part of BM)

139
Q

What role does fibronectin play?

A

In healing wounds, tissue and plasma fibronectin provide the scaffolding for subsequent ECM deposition, angiogenesis, and reepithelialization

140
Q

What group of proteins enforce the job of cell cycle checkoint?

A

CDK inhibitors and it does this by modulating CDK-cyclin complex activity

141
Q

CDKI p21, P27 and p57 inhibits which CDKs?

A

they broadly inhibit multple CDKS like CDK6, 2, and 1

142
Q

CDKI p15, p16, and p18 inhibits which CDKs?

A

CDK4 and CDK6

143
Q

Of the following CDK, Cyclin state which CDK pairs up with which cyclin and also state what phase of the cell cycle it controls by phosphorylating what proteins.
CDK: 4, 6, 2, 1
Cyclin: D, A, B, E
Check points: G1-S ; G2-M

A

Cyclin D-CDK4, Cyclin D-CDK6, and cyclin E-CDK2 regulates G1 to S transition by phosphorylating the Rb protein.

Cyclin A-CDK2; Cyclin A-CDK1 are active during S phase.

Cyclin B-CDK1 is essential for G2-to M transition.

144
Q

How do stem cells keep its properties as a stem cell?

A
  1. self-renewal

2. Asymmetric division

145
Q

Embryonic stem cells are derived from cells of what blastocyst?

A

inner cell mass

146
Q

Give an example of a multipotent stem cell.

A

mesenchymal stem cells which can differentiate into a variety of stomal cells including chondrocytes (cartilage), osteocytes (bone), adipocytes (fat), and myocytes (muscles)

MOD Exam I (4 decks)

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