SEMESTER 1 Flashcards
who created the microscope
Robert hooke (1635-1703)
how many cells in the body
approx. 37 trillion cells
what are archaea
formerly archaebacteria
many species live in extreme environments
components of the cytoskeleton
actin filaments
intermediate filaments
microtubules
role of the cytoskeleton
maintain shape and stability.
adaptation of shape .
cell division.
motility.
movement of particles within cells.
how big is a mitochondrion
0.5-1um in diameter and 1-2 um in length
what is a lysosome
single membrane bound organelle that degrade unwanted proteins and particles taken up by the cell, and membranes and organelles that are no longer needed
pH of a lysosome
4.5-5
what are peroxisomes
degrade fatty acids and toxic compounds
involved in fatty acid oxidation, produces precursors for biosynthetic pathways. (H202)
what catalysed the earliest evolution of life (LUCA)
small reactive molecules,
minerals as catalysts,
high temperatures in hydrothermal vents,
RNA world, ribozymes,
DNA more stable,
lipid bilayers spontaneously form vesicles
why is bacteria reproduction error prone
it is fast
endosymbiotic theory
eukaryotic cell engulfs bacterium and becomes an organelle
(mitochondria, chloroplasts from photosynthetic bacteria)
evidence for endosymbiosis form chloroplasts
photosystem I - similar to photosystem in green sulphur bacteria and heliobacteria
photosystem II - similar to photosystem of purple and green filamentous bacteria
what are protozoans
single celled eukaryotes, motility, predation, not animals, plants, or fungi
who discovered cholera is caused by a rod-shaped bacterium (Vibrio cholerae)
- Robert Koch (1884):
Who discovered penicillin
- Alexander Fleming (1928): Nobel Prize for Medicine 1945
do archaea cause disease?
no, they live in extreme environments
properties of viruses
outside of host cell,
retroviruses, lentiviruses - integration events can be mutagenic,
dormancy,
very small,
pandoravirus (2,500 genes) can be seen under microscope.
function of actin
defines shape of cells and sub-cellular structures.
exerts force.
cell movement.
cell division.
what is the most abundant protein in eukaryotic cells
actin 15%-10%
how many amino acids does actin have
375 (small)
what an actin bind
ATP/ADP
what causes muscular dystrophy and haemolytic anaemias
actin mutations
how does actin form a fibre
-pointed end (minus)
-barbed end (plus)
growth of fibres is slower at minus end than plus end
what regulates microfilament dynamics
approx. 60 actin binding proteins
how does actin operate during cell division
contractile actin-myosin ring that squeezes cells apart
classes of intermediate filaments
cytoplasmic: keratins (epithelia), vimentin (connective tissue, muscle cells, and glial cells) and vimentin-related, neurofilaments (nerve cells)
nuclear: nuclear lamins (in all animal cells)
function of intermediate filaments
structure and support against stretch.
provide support against mechanical stress.
what causes epidermolysis bullosa
mutations in Keratin
function of nuclear lamins
provide stability to the nucleus
what do microtubules do in cell division
push chromosomes to the midline then pull them to the poles
what are microtubules composed of
dimers of alpha and beta tubulin
13 parallel protofilaments
polarity: beta tubulin = plus end, polymerises faster
where do microtubules originate
MTOCs (microtubule organising centres) such as the centrosome
significant % of cancers have abnormal centrosomes
how is microtubule stability regulated
microtubule associated proteins
what are motor proteins
fall into 2 category’s
kinesins: transport cargo from minus end to plus end (of microtubule)
dyneins: plus to minus
what is the role of myosin-I
transport vesicles/organelle along actin fibre.
what is the basement membrane/basal lamina
2D sheet on which epithelial cells reside
fibrillar matrix
3D matrix composed of various fibres, in which cells such as fibroblasts are buried
what are the two types of extracellular matrix
basement membrane and fibrillar matrix
where do you find basement membrane
epithelium, muscle, kidney glomerulus
main components of fibrillar matrix
colagen I
fibronectin
elastin
proteoglycans
what is an occluding junction
seals different compartments away from each other ~(tight junction)
what is a cell-cell anchoring junctions
junctions that anchor cells to each other adherens junctions and desmosomes
what are cell matrix anchoring junctions
junctions that anchor cells to extracellular matrix (focal adhesion and hemidesmosome)
what is the difference between adherens junction and desmosome
both are cell cell anchoring junctions but desmosomes anchor to intermediate filaments and adherens junctions anchor to the actin filaments
what is the difference between focal adhesion and hemidesmosome
both are cell-matrix anchoring junctions but the hemidemmosome anchors to then intermediate filaments and focal adhesion anchors to actin filaments in the cell.
what are channel forming junctions
form connection between the cytoplasm of adjacent cells (gap junctions).
what do tight junctions do
turn epithelia into barriers
where are adherent junctions found on epithelial cells
in close proximity of tight junctions
how do adherens junctions help conduct morphological changes of tissues
contracting junction complexes in groups of cells (important in embryonic development)
function of lamellipodium
drive cell movement
how do cells move along basement membrane
actin filaments attach to different focal adhesions and pull the rest of the cell behind them in a crawling motion
what are cadherins
calcium dependent adhesion molecules
what are selectins
adhere white blood cells in vessels (leukocyte rolling)
how is cell adhesion involved in metastasis
tumour cells use specific mechanisms to undermine the tight sealing of epithelium and move through the blood stream to a another location and form a secondary tumour (metastasis)
what is a nissil body
clusters of neuronal endoplasmic reticulum (within the cell body (soma))
what are the dendrites of a neurone
antenna for information
what is an axon hillock
meeting point between cell body and axon where the action potential is generated
what is the axolemma
axon membrane
what is the unidirectional flow of the neutron
AP always travels from dendrites to cell body to axon
why are our brains poor in regenerating
neurones are post mitotic so can’t divide and our brains have limited active stem cells
what is the make up of the neuronal cytoskeleton and what are their functions?
microtubule: transport
neurofilaments: structural
microfilaments: structural + movement
what is the minus end and plus end of a neurone
cell body is the minus end and nerve endings are the plus ends
dynein in axonal transport
move towards minus end (cell body)
move 50-250mm/day
transport mitochondria, endocytotic vesicles
kinesin in axonal transport
move towards plus end (pre synaptic nerve endings)
move 100-400mm/day
transport mitochondria, neurotransmitter vesicles
how are axons myelinated by glial cells
glial cell sits on axon and extends membrane and wraps the membrane around many times
what’s multiple sclerosis
auto-immune disease where neurones undergo de-myelination
what are the coverings for nerve fibres
endoneurium - surround axon
perineurium - surround groups of axons called fascicles
epineurium - surround groups of fascicles
what is nissl staining
stains cell body, ER
what is a multipolar neurone
send out dendrites from the cell body in many directions
what are glial cells
non neuronal cells that are part of the nervous system
what are the major classes of glial cells
CNS:
ependymal cells
oligodendrocytes
astrocytes
microglia
PNS:
satellite cells
Schwann cells
what are astrocytes
most abundant glial cells in brain tissue
provide structural support
regulate extracellular electrolyte homeostasis
energy storage
what do oligodendrocytes do
myelinate axons in the CNS (multiple at once)
inhibit axon regeneration in the CNS
what do microglia do
provide immune defence in the brain
induce a pro-inflammatory reaction
can be activated and become phagocytitic
what are ependymal cells
line the fluid filled spaces in the brain
secrete , monitor and aid in the circulation of cerebrospinal fluid
cilia and micro villi
what is choroid plexus epithelium
specialised epithelium in all ventricles; secretes cerebro-spino fluid
what are Schwann cells
myelinate pns axons
remove myelin debris by phagocytosis
promote axon regeneration
what are satellite cells
PNS glial cells that provide structural and metabolic support
what is extracellular recording of electrical potential
electrode outside cell (group of cells)
what is intracellular recording of electrical potential
electrode inside cell (one cell)
what is patch clamping
electrode sealed to cell surface (single cell)
what is the equilibrium potential of an ion
the membrane voltage required to prevent movement of an ion down its concentration gradient
how do you measure the amount of work done at the membrane
Nernst equation:
E= 58(mV) x log [c]out / [c]in
how do you calculate concentration gradient
[c]out/ [c]in for +ve ions
[c]in / [c]out for -ve ions
membrane potential difference for K and Na
E(k) = -90mV (if above K will leave)
E(Na) = +50mV (if below Na will enter)
what can move across the lipid bilayer
small uncharged or hydrophobic molecules can freely transverse by simple diffusion
charged polar molecules require specialist proteins
what is secondary active transport across a membrane
requires an electrochemical gradient
e.g Na+/Glucose transporter (intestine)
what is the octane/water
partition coefficient
(Kow) ratio of how soluble a solute is in water compared to octanol
higher = more lipid soluble
components of K+ channel
ion filter
gate
example of mechanical gated channel
auditory receptors
what is the Jmax in a rate of uptake against external membrane concentration graphs
max rate of uptake of molecule
what is the Km in membrane transport
transporter affinity for substrate
lower Km higher affinity
where does the brain get all its energy
sugar
structure of GLUT1 glucose transporter
central cavity (aqueous cavity)
intracellular domains (latch)
what is SGLT1
sodium glucose symporters
intestinal epithelial cells for the absorption of dietary glucose
SGLT2: sodium-glucose symporters
sodium-glucose symporters
epithelial cells in proximal tubules of the kidney for reabsorption of glucose from the primary urine
how would you treat cholera with Na+/ glucose cotransporter
replacement therapy includes a high concentration of glucose , which drives Na+ back into the intestine through the Na+/glucose symporter, SGLT1
where does GLUT1 act
highly expressed in blood brain barrier, erythrocytes
where does GLUT2 act
liver, kidney, intestinal epithelium, pancreatic beta cells
where does GLUT 3 act
neurones
where does GLUT4 act
muscle, adipocytes
why are gap junctions important in neurones
smooth activation across cells
what is the width of a synapse
0.5 um
how are neurotransmitters removed from synapse
taken up by astrocytes and taken back up by presynaptic terminal
enzymes breakdown the molecule and taken into bloodstream or back to nerve
inotropic receptor
allows ions in
what is a graded potential
can be excitatory or inhibitory
gradual shift in charge following excitation
degrades over time and may not be strong enough to trigger AP along axon
temporal summation
one graded potential after another
second one adds to the first and threshold is reached
EPSP
excitatory postsynaptic potential
IPSP
inhibitory postsynaptic potential
metabotrapic receptors
combined to a G-protein
generates along-lasting more varied response
slower acting
spatial summation
addition of multiple graded potentials at once
somatic nervous system
motor fibres (general somatic efferens)
sensory fibres (general somatic afferens)
visceral (autonomic) nervous system
sympathetic = fight or flight
parasympathetic = rest and digest
motor fibres (general visceral efferens)
sensory fibres (general visceral afferens)
effect of parasympathetic nerves
constrict pupils
stimulate saliva
slow heart
constrict airways
stimulate activity of stomach
inhibit release of glucose; stimulate gallbladder
stimulate activity of intestines
contract bladder
project erection of genitals
effects of sympathetic nerves
dilate pupils
inhibit salivation
increase heartbeat
relax airways
inhibit activity of stomach
stimulate release of glucose; inhibit gall bladder
inhibit activity of intestines
secrete epinephrine and noradrenaline
relax bladder
promote ejaculation and vaginal contraction
anatomical directions
ventral forward (belly side)
dorsal back (back)
(rostral) anterior up (head)
(caudal) posterior down (feet)
planes of section
horizontal (flat)
coronal (crown)
sagital (middle part)
names for surfaces of the cerebrum
gyrus = ridges
sulcus = grooves
fissures = deep grooves
major subdivisions of the brain
forebrain
midbrain
hindbrain (pons, cerebellum, medulla)
spinal chord
4 lobes of brain
frontal lobe
parietal lobe
occipital lobe (vision)
temporal lobe (memory language)
how many pairs of spinal nerves
31
why is spinal chord shorter than vertebral column
spinal nerves hang down and leave at an angle
harder to damage
why is brain fluid filled
make brain less heavy
cushions entire brain
remove waste product
contains growth factors
how much cerebrospinal fluid do we produce each day
500ml normally reabsorbed into blood stream
if this pathway blocked = hydrocephalus
meningeal layers of CNS (protective)
pia mater (inner) tightly adhered
arachnoid mater (intermediate)
dura mater (outer)
CSF released between layers 1&2 the sub arachnoid space
how is cerebrospinal fluid recycled into the blood
via arachnoid granulations into venous blood
purpose of the cell cycle
copy genome and partition the copies equally between the daughter cells
enable a multicellular organism to grow to adult size
maintain total cell number of an adult organism
replace lost or damaged cells
prokaryote cell division
binary fission
DNA attached to cytoplasmic membrane (nucleoid)
cell enlarges and DNA duplicates
septum forms
cell divides in two
replication of DNA in prokaryotes
- circular chromosome has one origin of replication
-two replication forks form at the origin (bidirectional replication
-two identical copies of the circular chromosome
cytokinesis of prokaryote
-FtsZ distributed within cell
-FtsZ ring forms and contracts
-cell spits
how is the DNA replication speed brought up to the cytokinesis speed
-multiform replication
-replication of DNA initiated before completion of previous round
what is G1
growth phase, doubling the mass of organelles and protein, including synthesis of enzymes that will drive DNA replication
what is S phase
DNA synthesis phase. chromosome duplification
during the cell cycle how is premature chromosome separation prevented
after replication, sister chromatids are held together by cohesin
what is cohesin made up of
SMC3 and SMC1 and kleisin
what is G2
preparation for mitosis. the beginning of mitosis is marked by two events:
-chromosome condensation
-formation of mitotic spindle
what drives condensation of the chromosomes
condensin
how does condensin condense chromosomes
condensin encircles loops of DNA and compresses the sister chromatids to give a compact structure
what does the mitotic spindle bind to
kinetochore
-complex of proteins attached to the centromere
how is cohesin removed from sister chromatids
kleisin subunit of cohesin is cleaved by a protease
how do mitotic spindle have access to the chromosomes
during G2 the nuclear membrane breaks down and mitotic spindle can enter
what is the phragmoplast
guides synthesis of new cell wall in plant cell division
contains microtubules derived from the mitotic spindle
when is the cell cycle the shortest and why
early embryonic stages
division without growth
cell cycle time in liver
1 year
why do unicellular organism carry out closed mitosis
nuclear envelope remains intact throughout
spindle pole body is imbedded within the membrane
during mitosis what is distributed symetrically and symmetrically
DNA distributed symmetrically
cell fate determinants distributed asymmetrically
polarity in stem cell division
one cell is attached to niche cell and fated to retain its identity as a stem cell
and another cell is free to dissociate
what is contact inhibition
once cells contact each other they stop growing. inactivated in cancer cells
what does cyclin dependent kinase do
drive the phases of the cell cycle. it is the activity (not the levels) of the kinase that activate the phases of the cycle
what controls the activity of kinases
cyclin.
undergo cycles of synthesis and degradation so levels rise and fall
different CDKs and cyclins activate different phases
which cyclin activates G1/S CDK
cyclin E
what phase of cell cycle does G1/S CDK drive?
transition from G1 to S phase.
commits cell to the cycle
what cyclin does MCDK bind
cyclin B
what does M CDK do in the cell cycle?
promotes entry into mitosis.
activates condensin
induces nuclear membrane breakdown
how is the activity of M CDK diminished after mitosis
cyclin B degradation
G1 checkpoint
R (restriction point)
positive signal from the outside will instruct the cell to divide
G2/M checkpoint
is dna synthesis complete?
cell cycle is suspended if not
M checkpoint
is each chromosome attached to spindle?
what are anuploidies and trisomies
A: chromosome numbers other than 46
T: 3 copies of a chromosome
4 main types of intercellular communication
endocrine
paracrine
neuronal
contact dependent
what is autocrine signalling
special type of paracrine signalling where the secreting cell contains receptors for the secretory molecule
examples of signalling faces in cell signalling
hormones
growth factors
metabolic regulators
neurotransmitters
migratory cues
cell death factors
developmental patterning factors
intracellular receptors
either in the cytoplasm or in the nucleus
major membrane receptor families
ion channels
G-protein couples receptors
enzymes
G-protein couples receptors (GPCRs) structure
7 transmembrane domains
amino terminus in the exterior
carboxy terminus in the cytosol
functionality of GPCR
G protein is heterotrimeric which means it has 3 different subunits (alpha, beta and gamma)
A subunit is bound to GTP at rest, when signal binds GDP exchanges for GTP
G(alpha)-GTP activates effector enzyme adenyl cyclase which produces second messenger (cAMP)
what does cAMP do
activates protein kinase A PKA
what does protein kinase A do
phosphorylate proteins to make them functional active
has 2 subunits (regulatory and catalytic)
catalytic group phosphorylates proteins
atp phosphate donor
serine threonine kinase
what is a protein phosphatase
remove phosphate group from a protein and makes it inactive
what is protein kinase C
activated by adrenaline
(alpha 1 adrenergic receptor)
activated by ca ions and diacylglycerol
how is adrenaline able do have different effects
different receptors types for same ligand
effect of adrenaline on beta GPCR
2nd messenger:cAMP
causes glucose metabolism
effect of adrenaline on alpha 1 GPCR
2nd messenger DAG, IP3, Ca2+
causes contraction of smooth muscle
what is endocytosis
uptake of outside material(fluids and macromolecules) by invagination of the plasma membrane followed by pinching off and intracellular vesicle formation
mechanism of phagocytosis
-receptors that bind bacteria activated
-activation of F-actin polymerisation
-membrane protrudes and zippers around particle and phagosome sealed off
-F-actin disassembles
-fuses with lysosomes = phagolysosomes
degradation of content
function of macropinocytosis
uptake of fluid for feeding and removal of large number of growth factor receptors from plasma membrane
types of endocytosis
Cathrin mediated:
dynamin dependent - constitutive receptor-mediated, ligand induced receptor mediated
non-clathrin mediated:
dynamin-dependent- cave-in-mediated
dynamin-independent
Clathrin-mediated endocytosis function
receptor-mediated endocytosis allows the cell to take up specific macromolecules which are not abundant in the extracellular fluid via more than 25 different receptors
Cathrin mediated endocytosis: mechanism
egf receptor bings egf
adoption binds the inside of the receptor
bud formation
dynamin pinches off the vesicle (actin can contribute)
uncoating
what is dynamin
large protein that oligomerise into spirals
required for fission of vesicles
what is the functional unit of Cathrin
tryschelium
what mediates Cathrin cade disassembly
HSC70
auxilin
cytoplasmic pathway of a protein
-ribosome
-protein completed and released in folded form into cytoplasm (nucleus, peroxisome,cytoplasmic protein)
un folded protein transported to mitochondria where it is folded
where do endoplasmic reticulum pathway proteins get transported to
lysosomes, peroxisomes,new cytoplasmic membrane
secretory vesicles
what determines the pathway of proteins
endoplasmic reticulum signal sequence
what binds ER signal sequence to ER membrane
signal recognition particle SRP
destinations of ER pathway
-ER lumen
-further vesicular compartments
-secreted from cell
-embedded in membrane
what docks transport vesicle to plasma membrane
v-snare on vesicle and t-snare on target (membrane)
what are glycosyltranferases
enzymes in Golgi that add sugars to proteins
what three alleles of glycosyltransferases glycosylate the proteins on red blood cells
O, A, B
necrosis
traumatic cell death from acute injury
apoptosis
activation of a death programme
what causes apoptosis
-withdrawal of growth factors
-chemotherapy
-contact with cytotoxic T cells
-following a developmental programme
characteristics of necrosis
-membrane damage
-chromatin flocculation
-energy levels rapidly depleted
-leaking of cellular contents
-elicits an inflammatory response
apoptosis pathway
-chromatin condensation and membrane blebbing
-cell fragmentation (into apoptotic bodies)
-apoptopic bodies engulfed by phagocytes
why do apoptoses?
-during metamorphosis
-elimination of cells that have served their purpose
-cells infected by viruses
-cancer cells
-cells bearing excessive DNA damage
-promote self tolerance. auto reactive lymphocytes undergo apoptosis before they fully develop
where is DNA cut during apoptosis
DNA cleaved in linker regions between nucleosomes
how do we detect new free ends of DNA after apoptosis
TUNNEL assay
how does annexin V detect apoptosis cells
phosphotidile serine in plasma membrane flips and can be detected
why do phosphotidile serene lipids expose the the surface during apoptosis
this is a signal for phagocytes to bind and engulf the cell
what enzymes drive apoptosis in eukaryotes
capsases
what do caspases target
lamins
gelsolin (regulator of actin filament assembly/disassembly)
example of excess apoptosis
-heart attack
-type I diabetes Miletus
excitotoxicity
if excess glutamate is transported to a neurone it can cause unwanted cell death
how germ cells form in development
-primordial germ cells first seen in proximal epiblast pre-gastrulation.
-migrate to posterior during gastrulation
-migrate to gonads
-differentiate into egg or sperm
how meiosis ensures the gametes have the correct amount of genetic material
two cell divisions with DNA replication only taking place before the first division
how fertilisation occurs in mammals
-fusion between sperm and egg in the fallopian tube
-divides and forms a blastocyst which is then implanted into uterine wall
-sperm binds and penetrates zona pellucida
- plasma membrane of sperm fuses with egg plasma membrane
describe asexual reproduction in hydra
-little region buddy of the side of the embryo
-buds off and becomes its own organism
what is parthenogenesis
development of an embryo from an unfertilised egg cell
(haploid diploid bees)
cortical granule exocytosis
due to high Ca2+ granule membrane fuses with egg membrane
contents of granules released into space between cell membrane and vitelline envelope.
enzymes from cortical granules harden
innate immunity
non specific, rapid, response to infections, response to altered self
adaptive immunity
-specific
-slower to develop
-response to infections
-response to altered self
-can be humoural or cell mediated
-has memory
B vs T cells
Both arise from bone marrow and activated in secondary lymphoid organs and have a capacity to produce memory cells
B - mature in bone marrow, secrete antibodies
T - mature in thymus, induce a cell mediated response
antigen presenting cells
e.g dendritic cells
secondary lymphoid tissues
sites where immune responses are carried out
mesenchymal cells
connective tissue, bone, cartilage, fat
2 things stem cells must be able to do
self renew and differentiate
ensuring cultured cells are embryonic stem cells
-karyotyping
-expression of pluripotent markers
-differentiate
-transplant
reproductive cloning
enucleated egg + nucleus from somatic cell = egg with transplanted nucleus which develops into a clone of the nucleus donor
what are yamanaka factors
OCT4
SOX2
KLF4
C-MYC
The original set of reprogramming factors
antigen recognition
immunoglobin (secreted antibody and BCR) recognise whole antigen
TCR recognises processed antigen fragments presented by MHC
antibody segments
variable regions of the antibody are made up of two or three gene segments - VJ (kappa or lambda light chain) or VDJ (heavy chain)
