The cell as a Unit of health and disease Flashcards
Pathology literally translates as _______
The study of suffering
He was prescient in assrting that disease originates at the cellular level.
Virchow
Human genome contains some ________ billion DNA base pairs
3.2
Within the genome there are only about _____ protein-encoding proteins.
20000
These are the blueprints that instruct the assembly of enzymes, structural elements, and signalling molecules within the 50 trillion cells that make up the human body.
Noncoding DNA
___% of the human genome does not encode proteins
98.5
Regions that provide binding sites for transcription factors
Promoter and enhancer
2 best-studied varieties of noncoding regulatory RNA
MicroRNA
long noncoding RNA
jumping genes, can move around the genome during evolution, resulting in variable copy number and positioning even among closely related species.
mobile genetic elements
special structural regions of DNA
-chromosome ends
telomeres
special structural regions of DNA
-chromosome tethers
centromeres
Major component of centromere
satellite DNA
is also important in maintaining the dense, tightly packed organization of heterochromatin
satellite DNA
T or F
Variation in gene regulation may prove to be more important in disease causation than structural changes in specific proteins
True
Individual variation, including differential susceptibility to diseases and environmental stimuli, is encoded in less than __% of our DNA
0.5
2 of the most common forms of DNA variation in the human genome
- SNP
2. CNV
Variants at single nucleotide positions and are almost always biallelic
SNP
Roughly ___% of SNPs occur in coding regions
1
T or false
SNPs located in noncoding regions can occur within
genomic regulatory elements, thereby altering gene
expression; in such instances, SNPs influence disease
susceptibility directly.
T
are thought
to have no effect on gene function or individual
phenotype.
Neutral variants
are a form of genetic variation consisting of different
numbers of large contiguous stretches of DNA; these
can range from 1000 base pairs to millions of base pairs.
CNVs
Approximately __% of CNVs involve gene-coding
sequences; thus CNVs may underlie a large portion
of human phenotypic diversity.
50
Nucleosomes consist
of DNA segments 147 bp long that are wrapped around
a central core structure of highly conserved low molecular
weight proteins called ____
histones.
. The naked DNA of a single human cell is about
___long
1.8 m
In
general, only the regions that are ____ are available
for transcription.
“unwound”
T or False
Histones are static
False
Histones are not static, but rather are highly dynamic
structures regulated by a host of nuclear proteins.
____ complexes, on the other hand, carry out over 70
different histone modifications generically denoted as
“marks.”
“Chromatin
writer”
are associated with histone marks that make the DNA accessible
to RNA polymerases.
Actively transcribed genes
____ have
histone marks that enable DNA compaction into heterochromatin
inactive genes
Histone marks are reversible through the
activity of ____
“chromatin erasers.”
Histone methylation. Both ___ and ___can be
methylated by specific writer enzymes.
lysines; arginines
Lysine residues are acetylated by _____, whose modifications
tend to open the chromatin and increase transcription.
histone acetyltransferases (HATs)
changes can be reversed by histone deacetylases (HDACs), leading to chromatin ____
condensation.
Histone phosphorylation. ____residues can be modified
by phosphorylation
Serine
High levels of DNA methylation in
gene regulatory elements typically result in ____
transcriptional
silencing
are believed to bind to noncoding
regions and control long-range looping of DNA, thus
regulating the spatial relationships between enhancers
and promoters that control gene expression.
Chromatin organizing factors
T or F
Genes can also be regulated by noncoding RNAs.
True
do not encode proteins; they modulate translation
of target messenger RNAs (mRNAs)
Micro-RNA
T or F
Posttranscriptional
silencing of gene expression by miRNA is a fundamental
and well-conserved mechanism of gene regulation present
in all prokaryotes
False
-Eukaryotes
The human genome encodes almost ____ miRNA genes
6000
_____ are short RNA sequences
that can be introduced experimentally into cells where they
Small interfering RNAs (siRNAs)
finer granular structures of the nucleus
Euchromatin
means
that histones are not tightly wound.
Finely granular chromatin
■ cytochemically dense and transcriptionally inactive (they are not transcribed) ■ Coarsely granular structures of the nucleus
HETEROCHROMATIN
■ cytochemically dispersed and
transcriptionally active
■ Finely granular structures of the
nucleus
EUCHROMATIN
Functions primarily to modulate the translation of
target mRNA into their corresponding proteins
Micro-RNA (miRNA)
Transcription of miRNA genes produces a
primary transcript (pri-miRNA) that is
processed into progressively smaller segments,
including trimming by the ___
Dicer
they serve as
substrates for Dicer and interact with RISC,
thereby reproducing endogenous miRNAs
function.
Small interfering RNAs (siRNAs)
The number of lncRNAs may exceed coding
mRNAs by 10- to 20- fold
LONG NON-CODING RNA (lncRNA)
LONG NON-CODING RNA (lncRNA) modulate gene expression in many ways:
○ Gene activation
○ Gene suppression
○ Promote chromatin modification
○ Assembly of protein complexes
T or F
Many normal housekeeping functions are
compartmentalized within membrane-bound
intracellular organelles
True
synthesizes new proteins destined for
the plasma membrane or point beyond
which are physically assembled in the
Golgi apparatus
Rough endoplasmic reticulum (RER)
Synthesizes proteins intended for the
cytosol
Free ribosomes
SER may be abundant in ___ and ___
where it is used for steroid hormone and
lipoprotein synthesis;
gonads; liver
“Disposal” complexes that degrade
denatured or otherwise “tagged”
cytosolic proteins.
-can trigger initiation or suppression of signalling pathways
PROTEASOMES
Are intracellular organelles containing degradative enzymes that permit digestion of a wide range of macromolecules (proteins, polysaccharides, lipids, and nucleic acids.
LYSOSOMES
○ Contain catalase, peroxidase, and other oxidative enzymes ○ They play a specialized role in the breakdown of very long-chain fatty acids, generating hydrogen peroxide in the process.
PEROXISOMES
Shuttle internalized material to the
appropriate intracellular sites
Endosomal vesicles
Most of the adenosine triphosphate
(ATP) that powers cells is generated
via_____
Mitochondrial oxidative phosphorylation
also serve as an important source of
metabolic intermediates needed for
anabolic metabolism
Mitochondria
contain important sensors of cell
damage that can initiate and regulate
programmed cell death (e.g.,
apoptosis).
Mitochondria
Movement of both organelles and proteins within
the cell, as well as the entire cell in its
environment is accomplished by the
_____
cytoskeleton.
Cytoskeleton is composed of:
Filamentous actins (microfilaments), Keratins(intermediate filaments), and microtubules
○ 5 to 9nm diameter
○ formed from the globular protein actin
(G-actin)
○ most abundant
Actin microfilaments
New subunits are typically added at the
“positive” end of the strand and
removed from the “negative” end—a
process referred to as____
actin
treadmilling
○ 10nm diameter ○ predominantly form ropelike polymers and do not usually actively reorganize like actin and microtubules ○ provide tensile strength so that cells can bear mechanical stress, e.g., in epithelia ○ They form the major structural proteins of skin and hair.
Intermediate filaments
in mesenchymal
cells
Vimentin
in muscle cells forms
the scaffold on which actin
and myosin contract.
Desmin
are critical for
neuronal axon structure and
confer both strength and
rigidity.
Neurofilaments
is expressed in glial cells
Glial fibrillary acidic protein
are expressed in
epithelial cells
cytokeratins
are intermediate filament proteins that form the nuclear lamina, define nuclear shape, and can regulate transcription.
Lamins (A, B, and C) 7
○ 25nm thick ○ composed of noncovalently polymerized α- and β-tubulin dimers organized into hollow tubes ○ These fibrils are extremely dynamic and polarized, with “+” and “−” ends.
Microtubules
is typically embedded in a microtubule organizing center (MTOC or centrosome) near the nucleus, where it is associated with paired centrioles
“−” end
elongates or recedes
in response to various stimuli by
the addition or subtraction of
tubulin dimers
“+” end
anterograde (− to
+)
Kinesins
retrograde (+ to −)
Dyneins
PLASMA MEMBRANE ● a fluid bilayer of amphipathic phospholipids — hydrophilic head groups that face the \_\_\_\_\_ and hydrophobic lipid tails that \_\_\_\_\_\_
aqueous environment; interact with each other
○ inner membrane leaflet
○ serving as an electrostatic scaffold for
intracellular proteins
PHOSHATIDYLINOSITOL
polyphosphoinositides can be hydrolyzed by \_\_\_\_\_\_to generate intracellular second signals like diacylglycerol and inositol trisphosphate
phospholipase C
○ inner face
○ confers a negative charge involved in
electrostatic protein interactions
PHOSPHATIDYLSERINE
○ extracellular face
○ They are important in cell-cell and
cell-matrix interactions
GLYCOLIPIDS AND SPHINGOMYELIN
is involved in specialized pathways of protein/lipid transport and signaling. They also act as vesicular carriers for membrane trafficking in T lymphocytes.
Lipid raft
that binds one
cell to another
Cell-adhesion molecule
special integral membrane proteins called \_\_\_\_ form transmembrane channels for water, H2O2, and other small molecules.
aquaporins
T or F Larger hydrophobic molecules, (e.g., steroid-based molecules like estradiol or vitamin D) can also cross lipid bilayers with relative impunity
True
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
pumps polar compounds (e.g.,
chemotherapeutic drugs) out of cells
and may render cancer cells resistant to
treatment.
multidrug
resistance (MDR) protein
causes net movement
of water out of the cells.
Hypertonicity
causes net movement
of water into cells.
Hypotonicity
_____are most active at pH 7.4
and are often regulated by Ca2+, whereas
_____ function best at pH 5
or less.
Cytosolic enzymes ; lysosomal enzymes
○ For smaller molecules
○ “little caves”
Caveolae-mediated endocytosis
the major structural
protein of caveolae, which, like
membrane rafts, are enriched in
glycosphingolipids and cholesterol.
Caveolin
Internalization of caveolae along with
bound molecules and associated
extracellular fluid is called _____
potocytosis
Macromolecules bound to membrane receptors (such as transferrin or low-density lipoprotein [LDL] receptors) are taken up at specialized regions of the plasma membrane called \_\_\_\_
clathrin-coated pits.
T or F The vesicles then rapidly lose their clathrin coating and fuse with a basic intracellular structure called the early endosome
False
-not acidic, basic
In this process, proteins synthesized and packaged within the RER and Golgi apparatus are concentrated in secretory vesicles, which then fuse with the plasma membrane to expel their contents.
exocytosis
is the movement of endocytosed
vesicles between the apical and
basolateral compartments of cells
Transcytosis
Ganda ni quen no?
TRUE, siz!
