1: The Cell As A Unit Of Health And Disease

Question 1

Pathos =

Logos =

Answer 1

Pathos = SUFFERING

Logos = STUDY

Question 2

The human genome contains roughly ____________ DNA base pairs

Answer 2

The human genome contains roughly 3.2 billion DNA base pairs

Question 3

proteins variously function as??

Answer 3

proteins variously function as...
>enzymes
>structural components
>signaling molecules
>used to assemble and maintain all of the cells in the body

Question 4

nuclear  genetic  material  is  organized  into  dispersed transcriptionally active
_________________?

Answer 4

nuclear  genetic  material  is  organized  into  dispersed,  transcriptionally  active euchromatin  or  densely  packed

Question 5

nuclear  genetic  material  is  organized  into dense,  transcriptionally  inactive
_______________________?

Answer 5

nuclear  genetic  material  is  organized  into  dense transcriptionally  inactive  heterochromatin

Question 6

_____________________ can  only  be  visualized  by  light  microscopy  during  cell  division. During  _____________,  they  are  organized  into  paired  chromatids  connected  at  centromeres

Answer 6

Chromosomes  (as  shown)  can  only  be  visualized  by  light  microscopy  during  cell  division. During  mitosis,  they  are  organized  into  paired  chromatids  connected  at  centromeres

Question 7

_____________________  act  as  the  locus  for  the  formation  of  a  kinetochore protein  complex  that  regulates  chromosome  segregation  at what phase?

Answer 7

centromeres  act  as  the  locus  for  the  formation  of  a  kinetochore protein  complex  that  regulates  chromosome  segregation  at  metaphase

Question 8

The  ________repetitive  nucleotide  sequences  that  cap  the  termini  of  chromatids and  permit  repeated  chromosomal  replication  without  loss  of  DNA  at  the  chromosome  ends. 

Answer 8

  The  telomeres  are  repetitive  nucleotide  sequences  that  cap  the  termini  of  chromatids and  permit  repeated  chromosomal  replication  without  loss  of  DNA  at  the  chromosome  ends. 

Question 9

chromatids  are  organized  into…….?
_______

_______

Answer 9

chromatids  are  organized  into  short  “P”  (“petite”)  and  long “Q”  (“next letter in the alphabet”)  arms. 

Question 10

________________ are  noncoding  regions  of  DNA  that  initiate  gene  transcription

Answer 10

Promoters  are  noncoding  regions  of  DNA  that  initiate  gene  transcription

Question 11

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

Answer 11

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

Question 12

_________ of the human genome that does not encode proteins. It has been known for some time that protein-coding genes in higher organisms are separated by long stretches of DNA whose function has been obscure for many years—sometime denoted as “_______________” of the genome.

Answer 12

98.5% of the human genome that does not encode proteins. It has been known for some time that protein-coding genes in higher organisms are separated by long stretches of DNA whose function has been obscure for many years—sometime denoted as “dark matter” of the genome.

Question 13

___________________ of the genome that provide the critical “architectural planning.”

Answer 13

noncoding regions of the genome that provide the critical “architectural planning.”

Question 14

2 regions that provide binding sites for transcription factors?

Answer 14

Promoter and enhancer regions that provide binding sites for transcription factors

Question 15

___________________________ are  subsequently  spliced  out  of  the  pre-mRNA  to  produce  the  definitive  message  that  is  translated  into  protein—without  the  3′-  and  5′-untranslated regions  (UTR).

Answer 15

INTRONIC SEQUENCES  are  subsequently  spliced  out  of  the  pre-mRNA  to  produce  the  definitive  message  that  is  translated  into  protein—without  the  3′-  and  5′-untranslated regions  (UTR).

Question 16

“jumping genes”

Answer 16

Mobile genetic elements

E.g. TRANSPOSON

Question 17

Special structural regions of DNA?

Answer 17

telomeres (chromosome ends)

and

centromeres (chromosome “tethers”)

Question 18

2 most common DNA variation?

Answer 18

SNPs (Single Nucleotide Polymorphisms)

CNVs (Copy Number Variations)

Question 19

variants at single nucleotide positions and are almost always biallelic (i.e., only two choices exist at a given site within the population, such as A or T)?

Answer 19

SNPs (Single-Nucleotide Polymorphisms)

Question 20

more recently identified form of genetic variation consisting of different numbers of large contiguous stretches of DNA from 1000 base pairs to millions of base pairs?

Answer 20

CNV (Copy Number Variations)

Question 21

heritable changes in gene expression that are not caused by alterations in DNA sequence?

Answer 21

EPIGENETICS

Question 22

Nucleosomes consist of DNA segments 147 base pairs long that are wrapped around a central core structure of highly conserved low molecular weight proteins called ___________

Answer 22

Nucleosomes consist of DNA segments 147 base pairs long that are wrapped around a central core structure of highly conserved low molecular weight proteins called HISTONES

Question 23

series of beads joined by short DNA linkers and is generically called ____________

Answer 23

series of beads joined by short DNA linkers and is generically called CHROMATIN

Question 24

regulates gene expression and thereby dictates cellular identity and activity?

Answer 24

unwounded nuclear chromatin

Question 25

this carry out more than 70 different histone modifications generically denoted as MARKS

Answer 25

CHROMATIN WRITER COMPLEX

Question 26

Histone marks are reversible through the activity of ________

Answer 26

CHROMATIN ERASERS

Question 27

other proteins function as __________, binding histones that bear particular marks and thereby regulating gene expression.

Answer 27

CHROMATIN READERS

Question 28

methylation of lysine residues in histones may be associated with either transcriptional activation or repression, depending on the histone residue that is “marked”.

Answer 28

HISTONE METHYLATION

Question 29

_______________________ Lysine residues are acetylated by histone acetyl transferases (HAT), whose modifications tend to open up the chromatin and increase transcription. In turn, these changes can be reversed by histone deacetylases (HDAC), leading to ________________________________

Answer 29

HISTONE ACETYLATION CHROMATIN CONDENSATION

Question 30

___________________ Serine residues can be modified by phosphorylation; depending on the specific residue, the DNA may be opened up for transcription or condensed to become inactive.

Answer 30

HISTONE PHOSPHORYLATION

Question 31

__________________ tightly regulated by methyltransferases, demethylating enzymes, and methylated-DNA-binding proteins.

Answer 31

DNA METHYLATION

Question 32

which are believed to bind to noncoding regions and control long-range looping of DNA, which is important in regulating the spatial relationships between gene enhancers and promoters that control gene expression.

Answer 32

CHROMATIN ORGANIZING FACTORS

Question 33

are encoded by genes that are transcribed but not translated.

Answer 33

Micro-RNA and Long Noncoding RNA

Question 34

____________ do not encode proteins; instead, they function primarily to modulate the translation of target mRNAs into their corresponding proteins. its transcription produces _________ generates mature single-stranded miRNAs of 21 to 30 nucleotides that are associated with a multiprotein aggregate called _______________

Answer 34

miRNA primary miRNA RNA-induced silencing complex (RISC)

Question 35

All mRNAs contain a so-called __________ in their 3′ untrans-lated region (UTR) that determines the SPECIFICITY of miRNA binding and gene silencing. In this way, the target mRNA is posttranscriptionally silenced.

Answer 35

SEED SEQUENCE

Question 36

_____________ are short RNA sequences that can be introduced experimentally into cells. These serves as substrates for Dicer and interact with the RISC complex in a mannaer analogous to endogenous miRNAs.

Answer 36

Small interfering RNAs (siRNAs)

Question 37

a repressive function involves.... ________ which is transcribed from the X chromosome and plays an essential role in physiologic X chromosome inactivation. itself escapes X inacti-vation, but forms a repressive “cloak” on the X chromo-some from which it is transcribed, resulting in gene silencing.

Answer 37

XIST

Question 38

where new PROTEIN is SYNTHESIZED and physically ASSEMBLED in GOLGI APPARATUS

Answer 38

rough ER

Question 39

where LIPIDS are synthesized

Answer 39

smooth ER

Question 40

intracellular organelles that contain DEGRADATIVE enzymes that permit the digestion of a wide-range of macromolecules, including proteins, polysaccharides, lipids, and nucleic acids.

Answer 40

Lysosomes

Question 41

specialized type of “grinder” that selectively chews up denatured proteins, releasing peptides.

Answer 41

Proteasome

Question 42

play a specialized role in the breakdown of fatty acids, generating hydrogen peroxide in this process.

Answer 42

Peroxisome

Question 43

structural proteins also maintain basic cellular shape and intracellular organization, requisites for maintaining cell polarity.

Answer 43

Cytoskeleton

Question 44

Most of the ATP that powers cells is made through oxidative phosphorylation in the _________ . also serve as an important source of metabolic intermediates that are needed for anabolic metabolism

Answer 44

Mitochondria

Question 45

____________ fluid bilayers of amphipathic phospholipids with hydrophilic head groups that face the aqueous environment and hydrophobic lipid tails that interact with each other to form a barrier to passive diffusion of large or charged molecules

Answer 45

Plasma Membrane

Question 46

on the inner membrane leaflet can be phosphorylated, serving as an electrostatic scaffold for intracellular proteins ___________ can be hydrolyzed by phospholipase C to generate intracellular second signals like diacylglycerol and inositol trisphosphate.

Answer 46

Phosphatidylinositol

Question 47

__________________ normally restricted to the inner face where it confers a negative charge involved in electrostatic protein interactions when this flips to the extracellular face, which happens in cells undergoing apoptosis (programmed cell death), it becomes an “eat me” signal for phagocytes. In the special case of platelets, it serves as a cofactor in the clotting of blood.

Answer 47

Phosphatidylserine

Question 48

__________ and ____________ are preferentially expressed on the extracellular face ______________ (and particularly gangliosides, with complex sugar linkages and terminal sialic acids that confer negative charges) are important in cell-cell and cell-matrix interactions including inflammatory cell recruitment and sperm-egg interactions.

Answer 48

Glycolopid and Shingomyelin Glycolipid

Question 49

_____________________ typically contain positively charged amino acids in their cytoplasmic domains, which anchor the proteins to the negatively charged head groups of membrane phospholipids.

Answer 49

Integral membrane proteins

Question 50

_______________ functions as a chemical and mechanical barrier, and is also involved in cell-cell and cell-matrix interactions.

Answer 50

glycocalyx

Question 51

__________ these readily passes to lipid bilayers

Answer 51

hydrophobic substances

Question 52

_______________ create hydrophilic pores, which, when open, permit RAPID movement of solutes (usually restricted by size and charge)

Answer 52

Channel proteins

Question 53

_______________ bind their specific solute and undergo a series of conformational changes to transfer the ligand across the membrane; their transport is relatively SLOW

Answer 53

Carrier proteins

Question 54

concentration and/or electrical gradient between the inside and outside of the cell drives solute movement via what transport?

Answer 54

passive transport

Question 55

____________________ of certain solutes against a concentration gradient is accomplished by carrier molecules (not channels) using energy released by ATP hydrolysis or a coupled ion gradient.

Answer 55

active transport

Question 56

______________ also include the infamous multidrug resistance (MDR) protein, which pumps polar compounds (e.g., chemotherapeutic drugs) out of cells and may render cancer cells resistant to treatment.

Answer 56

Transporter ATPases

Question 57

___________ causes a net movement of water OUT of cells

Answer 57

hypertonicity

Question 58

_________ causes a net movement of water INTO cells.

Answer 58

hypotonicity

Question 59

Uptake of fluids or macromolecules by the cell

Answer 59

Endocytosis

Question 60

invaginations of the plasma membrane

Answer 60

caveole

Question 61

For bigger molecules, uptake occurs after binding to specific cell-surface receptors; internalization occurs through a membrane invagination process driven by an intracellular coat of __________

Answer 61

CLATHRIN PROTEINS

Question 62

exported molecules FROM the cells via ___________

Answer 62

Exocytosis

Question 63

______________ is the movement of endocytosed vesicles between the apical and basolateral compartments of cells; this is a mechanism for transferring large amounts of intact proteins across epithelial barriers (e.g., ingested antibodies in maternal milk across intestinal epithelia) or for the rapid movement of large volumes of solute.

Answer 63

Transcytosis

Question 64

_____________, Caveolae (“little caves”) are noncoated plasma membrane invaginations associated with GPI-linked molecules, cyclic adenosine monophosphate (cAMP) binding proteins, SRC-family kinases, and the folate receptor

Answer 64

Caveolae-mediated endocytosis

Question 65

major structural protein of caveolae

Answer 65

Caveolin

Question 66

Internalization of caveolae with any bound molecules and associated extracellular f luid is sometimes called _______________ —literally “cellular sipping.”

Answer 66

potocytosis

Question 67

____________ ( “cellular drinking”) describes a fluid-phase process during which the plasma membrane invaginates and is pinched off to form a cytoplasmic vesicle. starts with _________

Answer 67

Pinocytosis clathrin-coated pit clathrin-coated vesicles

Question 68

____________________ is the major uptake mechanism for certain macromolecules, as exemplified by transferrin and low-density lipoprotein (LDL).

Answer 68

Receptor-mediated endocytosis

Question 69

The ability of cells to adopt a particular shape, maintain polarity, organize the relationship of intracellular organelles, and move about depends on the intracellular scaffolding of proteins called the ______________________

Answer 69

cytoskeleton

Question 70

___________ 5-9 mm example ___________ 10mm example ___________ 25mm

Answer 70

microfilament e.g actin filament (G & F actin) intermediate e.g > Lamin A, B, and C: nuclear lamina of all cells > Vimentin: endothelium, mesenchymal cells > Desmin: muscle cells, forming the scaffold on which actin and myosin contract > Neurofilaments: axons of neurons, imparting strength and rigidity > Glial fibrillary acidic protein: glial cells around neurons > Cytokeratins ``` Microtubules e.g > motor proteins: (kinesin- anterograde transport) (dynein- retrograde transport) ```

Question 71

cell to cell interaction?

Answer 71

cell junctions

Question 72

cell junction types???

Answer 72

``` occluding junction (tight) e.g occludin, claudin, zonulin, and catenin ``` anchoring junction (desmosomes) - cadherins e.g > spot desmosome/macula adherens - When the adhesion focus is between cells, and is small and rivet-like. (cadherins are called desmoglein or desmocollin) > hemidesmosome - When such a focus attaches the cell to the ECM, it is called a hemidesmosome. (cadherins are called integrins) > belt desmosome -Similar adhesion domains can also occur as broad bands between cells (cadherins are called E-cadherins) ``` communicating junctions (gap junctions) e.g connexons < connexins ```

Question 73

site for synthesis of all the transmembrane proteins and lipids for plasma membrane and cellular organelles, including ER itself.

Answer 73

ENDOPLASMIC RETICULUM

Question 74

ER + ribosomes _________ ER - ribosomes __________

Answer 74

Rough ER Smooth ER

Question 75

__________ retain proteins in the ER until these modifications are complete and the proper conformation is achieved.

Answer 75

Chaperone molecules

Question 76

excess accumulation of misfolded proteins—exceeding the capacity of the ER to edit and degrade them—leads to the _____________ (also called the ___________ or UPR) that triggers cell death through ____________

Answer 76

ER stress response unfolded protein response apoptosis

Question 77

From the RER, proteins and lipids destined for other organelles or for extracellular export are shuttled into the _______________ This organelle consists of stacked cisternae that progressively modify proteins in an orderly fashion from cis (_______) to trans (_______)

Answer 77

Golgi apparatus near the ER near the plasma membrane

Question 78

____________ can recycle proteins BACK to the ER; ____________ sorts proteins and lipids and DISPATCHES them to other organelles (including the plasma membrane), or to secretory vesicles destined for extracellular release.

Answer 78

cis Golgi network trans Golgi network

Question 79

Senescent organelles and large, denatured pro tein complexes are shuttled into lysosomes by a process called ________________

Answer 79

autophagy

Question 80

the membrane progressively expands to encircle a collection of structures and forms an ___________ which then fuses with lysosomes and the contents are catabolized.

Answer 80

autophagosome

Question 81

___________ of microorganisms or large fragments of matrix or debris occurs primarily in professional phagocytes (_______ or ________). The material is engulfed to form a _____________ that subsequently fuses with a lysosome.

Answer 81

Phagocytosis macrophages or neutrophils phagosome

Question 82

__________ play an important role in degrading cytosolic proteins

Answer 82

Proteasomes

Question 83

programmed cell death

Answer 83

apoptosis

Question 84

Outside the ___________ is the intermembrane space, site of ATP synthesis, which is, in turn, enclosed by the ___________

Answer 84

inner membrane outer membrane

Question 85

_____________: External cellular injury (toxin, ischemia, trauma) can damage mitochondria, inducing the formation of mitochondrial permeability transition pores in the outer membrane. These channels allow the dissipation of the proton potential so that mitochondrial ATP generation fails and the cell dies. ___________: Programmed cell death is a central feature of normal tissue development and turnover and can be triggered by ___________ signals (including cytotoxic T cells and inflammatory cytokines), or ____________ pathways (including DNA damage and intracellular stress).

Answer 85

Necrosis Apoptosis > extrinsic > intrinsic

Question 86

Loss of cellular communication and the “social controls” that maintain normal relationships of cells can variously lead to unregulated growth (______) or an ineffective response to an extrinsic stress (as in _______).

Answer 86

cancer shock

Question 87

Contact with neighboring cells

Answer 87

junctions

Question 88

contact with ECM

Answer 88

integrins

Question 89

________ Cells in just the immediate VICINITY are affected.

Answer 89

Paracrine signaling

Question 90

______________ occurs when molecules secreted by a cell affect that SAME CELL.

Answer 90

Autocrine signaling

Question 91

_____________ Activated neurons secrete neurotransmitters at specialized cell junctions (SYNAPSES) onto target cells.

Answer 91

Synaptic signaling

Question 92

______________ A mediator is released into the BLOODSTREAM and acts on target cells AT A DISTANCE

Answer 92

Endocrine signaling

Question 93

signal it conveys is transmitted to the cell via a specific ______________.

Answer 93

receptor protein

Question 94

Signaling molecules (________) bind their respective receptors and initiate a cascade of intracellular events culminating in the desired cellular response.

Answer 94

ligands

Question 95

____________ are transcription factors that are activated by lipid-soluble ligands that can easily cross the plasma membrane

Answer 95

Intracellular receptors

Question 96

________________ are generally transmembrane proteins with extra cellular domains that bind soluble secreted ligands. Depending on the receptor, ligand binding can then (1) open ion channels (typically at the synapse between electrically excitable cells) (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 a change in protein binding or stability that activates a latent transcription factor. Activities (2) and (3) are associated with growth factor signaling pathways that drive cell proliferation, while activity (4) is a common feature of multiple pathways (e.g., Notch, Wnt, and Hedgehog) that regulate normal development.

Answer 96

Cell-surface receptors