1: The Cell As A Unit Of Health And Disease Flashcards
Pathos =
Logos =
Pathos = SUFFERING
Logos = STUDY
The human genome contains roughly ____________ DNA base pairs
The human genome contains roughly 3.2 billion DNA base pairs
proteins variously function as??
proteins variously function as... >enzymes >structural components >signaling molecules >used to assemble and maintain all of the cells in the body
nuclear genetic material is organized into dispersed transcriptionally active
_________________?
nuclear genetic material is organized into dispersed, transcriptionally active euchromatin or densely packed
nuclear genetic material is organized into dense, transcriptionally inactive
_______________________?
nuclear genetic material is organized into dense transcriptionally inactive heterochromatin
_____________________ can only be visualized by light microscopy during cell division. During _____________, they are organized into paired chromatids connected at centromeres
Chromosomes (as shown) can only be visualized by light microscopy during cell division. During mitosis, they are organized into paired chromatids connected at centromeres
_____________________ act as the locus for the formation of a kinetochore protein complex that regulates chromosome segregation at what phase?
centromeres act as the locus for the formation of a kinetochore protein complex that regulates chromosome segregation at metaphase
The ________repetitive nucleotide sequences that cap the termini of chromatids and permit repeated chromosomal replication without loss of DNA at the chromosome ends.
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.
chromatids are organized into…….?
_______
_______
chromatids are organized into short “P” (“petite”) and long “Q” (“next letter in the alphabet”) arms.
________________ are noncoding regions of DNA that initiate gene transcription
Promoters are noncoding regions of DNA that initiate gene transcription
__________________
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.
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.
_________ 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.
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.
___________________ of the genome that provide the critical “architectural planning.”
noncoding regions of the genome that provide the critical “architectural planning.”
2 regions that provide binding sites for transcription factors?
Promoter and enhancer regions that provide binding sites for transcription factors
___________________________ 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).
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).
“jumping genes”
Mobile genetic elements
E.g. TRANSPOSON
Special structural regions of DNA?
telomeres (chromosome ends)
and
centromeres (chromosome “tethers”)
2 most common DNA variation?
SNPs (Single Nucleotide Polymorphisms)
CNVs (Copy Number Variations)
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)?
SNPs (Single-Nucleotide Polymorphisms)
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?
CNV (Copy Number Variations)
heritable changes in gene expression that are not caused by alterations in DNA sequence?
EPIGENETICS
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 ___________
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
series of beads joined by short DNA linkers and is generically called ____________
series of beads joined by short DNA linkers and is generically called CHROMATIN
regulates gene expression and thereby dictates cellular identity and activity?
unwounded nuclear chromatin
this carry out more than 70 different histone modifications generically denoted as MARKS
CHROMATIN WRITER COMPLEX
Histone marks are reversible through the activity of ________
CHROMATIN ERASERS
other proteins function as __________, binding histones that bear particular marks and thereby regulating gene expression.
CHROMATIN READERS
methylation of lysine residues in histones may be associated with either transcriptional activation or repression, depending on the histone residue that is “marked”.
HISTONE METHYLATION
_______________________ 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 ________________________________
HISTONE ACETYLATION
CHROMATIN CONDENSATION
___________________ 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.
HISTONE PHOSPHORYLATION
__________________ tightly regulated by methyltransferases, demethylating enzymes, and methylated-DNA-binding proteins.
DNA METHYLATION
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.
CHROMATIN ORGANIZING FACTORS
are encoded by genes that are transcribed but not translated.
Micro-RNA and Long Noncoding RNA
____________ 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 _______________
miRNA
primary miRNA
RNA-induced silencing complex (RISC)
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.
SEED SEQUENCE
_____________ 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.
Small interfering RNAs (siRNAs)
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.
XIST
where new PROTEIN is SYNTHESIZED
and physically ASSEMBLED in GOLGI APPARATUS
rough ER
where LIPIDS are synthesized
smooth ER
intracellular organelles that contain DEGRADATIVE enzymes that permit the digestion of a wide-range of macromolecules, including proteins, polysaccharides, lipids, and nucleic acids.
Lysosomes
specialized type of “grinder” that selectively chews up denatured proteins, releasing peptides.
Proteasome
play a specialized role in the breakdown of fatty acids, generating hydrogen peroxide in this process.
Peroxisome
structural proteins also maintain basic cellular shape and intracellular organization, requisites for maintaining cell polarity.
Cytoskeleton
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
Mitochondria
____________ 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
Plasma Membrane
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.
Phosphatidylinositol
__________________ 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.
Phosphatidylserine
__________ 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.
Glycolopid and Shingomyelin
Glycolipid
_____________________ typically contain positively charged amino acids in their cytoplasmic domains, which anchor the proteins to the negatively charged head groups of membrane phospholipids.
Integral membrane proteins
_______________ functions as a chemical and mechanical barrier, and is also involved in cell-cell and cell-matrix interactions.
glycocalyx
__________ these readily passes to lipid bilayers
hydrophobic substances
_______________ create hydrophilic pores, which, when open, permit RAPID movement of solutes (usually restricted by size and charge)
Channel proteins
_______________ bind their specific solute and undergo a series of conformational changes to transfer the ligand across the membrane; their transport is relatively SLOW
Carrier proteins
concentration and/or electrical gradient between the inside and outside of the cell drives solute movement via what transport?
passive transport
____________________ 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.
active transport
______________ 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.
Transporter ATPases
___________ causes a net movement of water OUT of cells
hypertonicity
_________ causes a net movement of water INTO cells.
hypotonicity
Uptake of fluids or macromolecules by the cell
Endocytosis
invaginations of the plasma membrane
caveole
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 __________
CLATHRIN PROTEINS
exported molecules FROM the cells via ___________
Exocytosis
______________ 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.
Transcytosis
_____________, 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
Caveolae-mediated endocytosis
major structural protein of caveolae
Caveolin
Internalization of caveolae with any bound molecules and associated extracellular f luid is sometimes called _______________ —literally “cellular sipping.”
potocytosis
____________ ( “cellular drinking”)
describes a fluid-phase process during which the plasma membrane invaginates and is pinched off to form a cytoplasmic vesicle.
starts with _________
Pinocytosis
clathrin-coated pit
clathrin-coated vesicles
____________________ is the major uptake mechanism for certain macromolecules, as exemplified by transferrin and low-density lipoprotein (LDL).
Receptor-mediated endocytosis
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 ______________________
cytoskeleton
___________ 5-9 mm
example
___________ 10mm
example
___________ 25mm
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)
cell to cell interaction?
cell junctions
cell junction types???
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
site for synthesis of all the transmembrane proteins and lipids for plasma membrane and cellular organelles, including ER itself.
ENDOPLASMIC RETICULUM
ER + ribosomes _________
ER - ribosomes __________
Rough ER
Smooth ER
__________ retain proteins in the ER until these modifications are complete and the proper conformation is achieved.
Chaperone molecules
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 ____________
ER stress response
unfolded protein response
apoptosis
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 (_______)
Golgi apparatus
near the ER
near the plasma membrane
____________ 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.
cis Golgi network
trans Golgi network
Senescent organelles and large, denatured pro tein complexes are shuttled into lysosomes by a process called ________________
autophagy
the membrane progressively expands to encircle a collection of structures and forms an ___________ which then fuses with lysosomes and the contents are catabolized.
autophagosome
___________ 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.
Phagocytosis
macrophages or neutrophils
phagosome
__________ play an important role in degrading cytosolic proteins
Proteasomes
programmed cell death
apoptosis
Outside the ___________ is the intermembrane space, site of ATP synthesis, which is, in turn, enclosed by the ___________
inner membrane
outer membrane
_____________: 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).
Necrosis
Apoptosis
> extrinsic
> intrinsic
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 _______).
cancer
shock
Contact with neighboring cells
junctions
contact with ECM
integrins
________ Cells in just the immediate VICINITY are affected.
Paracrine signaling
______________ occurs when molecules secreted by a cell affect that SAME CELL.
Autocrine signaling
_____________ Activated neurons secrete neurotransmitters at specialized cell junctions (SYNAPSES) onto target cells.
Synaptic signaling
______________ A mediator is released into the BLOODSTREAM and acts on target cells AT A DISTANCE
Endocrine signaling
signal it conveys is transmitted to the cell via a specific ______________.
receptor protein
Signaling molecules (________) bind their respective receptors and initiate a cascade of intracellular events culminating in the desired cellular response.
ligands
____________ are transcription factors that are activated by lipid-soluble ligands that can easily cross the plasma membrane
Intracellular receptors
________________ 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.
Cell-surface receptors
