MTM Flashcards
What does RER do?
Synthesis and fold proteins
What does SER do?
Synthesis of lipid and phospholipid
Golgi apparatus function…
Add things in
Fold
Package
Why does mitochondria need a double membrane?
Chemiosmotic gradient
Lysosome functions
Degrade proteins with enzymes
Peroxisomes function
Absorb toxic substances
Hydrogen peroxides
Lipids
Microtubules function
Moving organelles around, hold in position
Directing traffic
Why is having a cytoskeleton important?
Keep in the right format
And orientation
Eg So villi at top of cell
Protein structure
Primary- amino acid sequence
Secondary- initial folding
Tertiary- 3d shape (that required the lowest energy)
Quaternary- more than one polypeptide chain
Side chains can be…
Charged (positive and negative)
Non-polar, aliphatic
Polar, uncharged
Aromatic
Aliphatic
Not aromatic
Straight or branched chains
Alpha helices structure
Helix
Vertical hydrogen bonds between molecules
R groups face outwards
Beta pleated sheets
R above or below
Folded sheet
Hydrogen bonds adjacent
What is globular useful for?
Secretion
Protein functions
Regulatory
Catalytic
Substrate binding/modification
Contact gene expression proteins
Bonds to specific DNA sequence
Etc
Regulation of protein function (the steps)
Synthesis
Localisation
Modification
Degradation
How are proteins localised?
Mostly all synthesised in rER
Contains sorting signal to direct to correct site
Move via transporters in membrane
The secretory pathway, how are substances secreted?
Via transport vesicles
Some have secretory vesicles
where does Protein modification occur?
Mostly done in rER (disulphide and glycosylation)
Anything else in Golgi apparatus
What is the four types of tissue?
Muscle
Nervous
Epithelia
Connective
Basal lamina is…
(Basement membrane)
Specialised form of extracellular matrix
How can the basal lamina be arranged in tissues?
Surround cells
Lies under sheets of epithelial cells
Separates two sheets of cells
Functional importance of basal lamina
Barrier
Molecular filter/prevent paracellular transport
Separate nerve from muscles at NMJ
Regenerate synapse after injury
Support
Limits contact
what is Mucousa?
The lining of different tracts/tubes
Epithelial cells secrete mucus (loose connective tissue)
what is Cell polarity?
Intrinsic asymmetry
Two key poles of epithelial cells
Base
Apex
Lateral membrane is…
Sides of cell contacting neighbouring cells
Types of intercellular junctions:
- Zonula occuldens
- Zonula adherens
- Macula adherens
- Gap junctions
- Hemidesmosomes
What is a Zonula occludens?
Cell junction
Most apical (top)
Super tight
What is a Zonula adheren?
Belt desmosome
Below ZO not as close as
What is a macula adheren?
Spot desmosome
Super common
Spot-welds
ZO and ZA and MA called junction complex
What is a gap junction?
Not so much for adhesion
More for allowing ions/molecules to pass
What is a hemidesmosome?
Not a cell-cell junction
Cell-basement junction
What are cell membrane composed of?
Mainly Phospholipids and proteins
Two sheets- bilayer
Proteins for signalling, communication and selective permeability
Four major phospholipids
Phosphatidyl-ethanolamine
Phosphatidyl-serine
Phosphatidyl-choline
Sphingomyelin
Intracellular signal transduction lipids
Phosphatidylinositol
Diacylglycerol
Ceramide
Sphingosine-1-phosphate
Transcription direction
RNA synthesised in the 5’ to 3’ direction
Template strand
Attaches to RNA molecules
Coding strand
Has same sequence as RNA (exception of uracil)
Splicing
RNA processing
Removed introns
Splicing requires…
RNA protein complexes
Called snRNP
RNA cap
Added to mRNA
Ribosome structure
Large and small subunit
mRNA binding site
P- site
A -site
tRNA carry…
Amino acids
P site is for…
Peptidyl-tRNA
A site for…
Aminoacyl-tRNA
tRNA structure
Codon
Anticodon
Polyribosome
When multiple ribosome attach to the the mRNA
Start site
AUG
The genetic code
Read in groups of 3
5’ to 3’
3 possible reading frames
Amino acids coded by a codon
Some have more than one codon
Some codons do not code amino acids(stop codons)
Universal
Mutations
Deletion
Insertion
Substitution/point mutations
Genes are transcriptional units made of:
Structural information to code for a protein
Regulatory sequences giving instructions for expression
Promoter region
A sequence right before the coding sequence
Enhancer region
A far from gene (upstream)
Gene regulatory proteins will bind to
Nucleosomes
11nm
Beads on a string
Basic units of chromatin
DNA wrapped around protein core
Protein core
8 histones
Linker
60 base pairs between histones
Histone tails function
Chemical modifications
Regulatory information
Acetylation/methylation
Ubiquitilation
Ubiquitine added to lysine
Histone acetylene transferases
Adds acetyl
Histone de-acetylases
Takes off acetyl
Epigenetics
Modifications of histones
X-inactivation
At blastocyst cells
Some cells inactivate one X chromosome and other cells the other
Random
Passed on to daughter cells
Metabolism definition
The chemical processes that occur within a living organism to maintain life
Catabolic pathway
Break down complex molecules into simple molecules and release energy
Anabolic pathways
Build complex molecules from simple and require energy (usually ATP)
Glucose metabolism
A series of reaction involving several metabolic pathways
Where are glycolysis, PPP, fatty acid synthesis conducted?
Cytosolic
Where are energy metabolism related pathways located?
Mitochondria
Where are TCA enzymes located?
Mitochondrial matrix
Apart from sic image dehydrogenase (inner membrane)
Oxidation
Gain of oxygen
Loss of electrons
Reduction
Loss of oxygen
Add electrons
Hydrolysis
Dehydration
Add/remove water
Phosphorylation
Add phosphate
Carboxylation
Add CO2
Ligation reaction
Formation of acetyl-CoA or succinyl-CoA
Where does ATP release its energy?
The 2 phosphoanhydride bonds
Releases 7.3 kcal
Steps of ATP production
Glycolysis
Oxidative decarboxylation of pyruvate
TCA cycle
Electron transport chain
Overall yield of glycolysis
Glucose -> 2 pyruvate
2ADP -> 2ATP
2NAD+ -> 2NADH
glucose to fructose 1,6 bisphosphate
(reaction type and enzyme)
two phosphorylations (hexokinase/phosphofructokinase)
one isomerisation (phosphoglucose isomerase)
f16bp is split
glyceraldehyde 3 phosphate
oxidoreduction- phosphorylation of GA-3-P to pyruvate (products)
GA-3-P
1,3 bisphosphoglycerate
3 phosphoglycerate
2 phosphoglycerate
phosphoenolpyruvate
pyruvate
oxidoreduction- phosphorylation enzymes
glyceraldehyde 2-phosphate dehydrogenase
phosphoglycerate kinase
phosphoglyceromutase
enolase
pyruvate kinase
anaerobic respiration
pyruvate to lactate
to regenerate NAD+
anaerobic respiration enzyme
lactate dehydrogenase
gluconeogenesis in liver and anaerobic respiration
cori cycle
gluconeogenesis energy cost
2 pyruvate
4 ATP
2 GTP
2NADH
= 1 glucose
reversible steps in glycolysis…
use the same enzymes in gluconeogenesis
pyruvate dehydrogenase function
mediates pyruvate decarboxylation
coverts pyruvate to acetyl coA
pyruvate decarboxylation net gain
1 CO2 produced
NAD+ reduced to NADH
how can acetyl CoA be made?
from amino acids
pyruvate
or fatty acids (reversible)
is pyruvate dehydrogenase reversible?
no
committed to aerobic
intracellular signal lipids
how do they work?
derived from plasma membrane lipids
rapidly generated
destroyed by enzymes in response
highly specific
binds to conversed regions within many different proteins
induce conformational/localised activity
cholesterol function
tightens packing
decreases membrane permeability
no effect to fluidity
what is the job of the polar head on cholesterol?
orients it in the membrane
why is it important that membranes are fluid?
signalling lipids/proteins to rapidly diffuse and interact
ensure membranes are equally shared between daughter cells
allow membranes to use for eg exocytosis
types of transmembrane proteins
single pass
multipass
b-barrel
peripheral membrane protein types
lipid linked
integrated with integral proteins
membrane protein function
transport
enzymatic activity
signal transduction
cell-cell recognition
intercellular joining
attachment to extracellular matrix/cytoskeleton
factors that effect simple diffusion
conc gradient
hydrophobicity
charge
size
why do cells maintain electrochemical gradients?
drive transport across membranes
maintain osmotic balance
Na+/K+ ATPase mechanism
3 Na+ bind
pump hydrolyses ATP and is phosphorylated
undergoes conformational change 3Na+ release
2K+ bind
pump dephosphorylated so returns to original shape
3 types of active transport
ATP-driven pumps
coupled transporters
light driven pumps
what is histology?
study of tissues to see arrangement/abnormalities/drug action
what are the steps to studying tissues?
fixation
dissection
sectioning
staining
visualisation
most common stain
haematoxylin
eosin
what does haematoxylin bind to?
acidic
what does eosin bind to?
basic
masson’s trichrome stains
nuc: purple
cyt: brick red
connective: green or blue
elastic van gieson stains
nuc: grey-blue
cyt: green-yellow
collagen: red
elastin: black
two types of epithelium
covering
glandular
basic structure of epithelial cells
apical up
basal down connected to basement membrane
connect adjacent by desmosomes and hemidesmosomes
layers of basement membrane
lamina lucida
lamina densa
reticular lamina
nomenclature of epithelial cells
number, shape, specialisation
number of epithelial cells
1 = simple
>1 = stratified
shape of epithelial cells
cuboidal
columnar
squamous
specialisations of epithelial cells
ciliated
keratinised
exceptions of epithelial naming
pseudo stratified: looks like multiple due to different heights but is only one layer of cells
transitional: eg urothelium
shape of cells change, look for umbrella cells
structure of epithelial cells
apical- specialisation
basal- anchor to membrane (receive nutrients/nervous innervation)
lateral- connect cells, cell junctions
cilia overview
made of: microtubules
10 micrometers
motile
only in few places- respiratory/reprodcutive
microvilli overview
made of actin
1 micrometre
less motile
widespread so not a specialisation that is named
keratinisation
certain squamous cells
excess produced
cells mature and keratin then left behind
keratin properties
cytoskeleton protein
strong but flexible
impermeable to water
4 phases of the cell cycle
G1 phase
S phase
G2 phase
M phase
3 checkpoint locations
entering s phase
g2
mitosis
quiescence
no activity
G0
restriction point criteria (at G0)
growth factors
1st checkpoint criteria
check for damaged DNA
2nd checkpoint criteria
incomplete DNA replication
3rd checkpoint criteria
spindle attachment failure
what is the cell cycle influenced by?
growth factors
growth inhibitory proteins
nutrients status
cyclin dependent kinase functions
regulate cell cycle checkpoint transitions
regulated by feedback themselves
kinases
an enzyme that activates/deactivates a protein by phosphorylating them
m-cdk does what?
switches itself off by initiating a process which leads to destruction of cyclin
how does a cyclin get activated?
remains inactive until it associates with new cyclin that is synthesised during interphase
restriction point is regulated by which protein?
retinoblastoma protein (pRB)
what can happen if pRB is mutated?
tumour in retina
as tumour supressor gene not activated
what are the proteins involved checkpoint 1?
p53 increase if damaged DNA
activates p21
this inhibits Cdk
so no S phase
what happens if the checkpoints fail?
proliferation of cells
replicate damaged DNA
segregation of incompletely replicated chromosomes
division of cells with the wrong number of chromosomes
growth factor signalling pathway
attaches to particular RTK (receptor tyrosine kinases)
recruits a RAS-activating protein
stimulates RAS to exchange GDP to GTP
oncogenic
involved in the origin or development of cancer/tumours
ways that gf pathways can come oncogenic?
receptors over active
signalling/ras protein is always on
over-expression of Mac transcription
carcinoma
abnormal cells that divide uncontrollably in epithelium
dysplasia
presence of abnormal cells that are not cancerous but could become so
metaplasia
one kind go cell transitioning to become another kind
neoplasia
mass of tissues that has accumulated when cells do not stop dividing or do not die
classic location of simple columnar
stomach
classic location of simple cuboidal
kidney tubules
classic location of simple squamous
blood vessel endothelium
classic location of ciliated simple columnar
respiratory tract
classic location of ciliated pseudo stratified columnar
respiratory tract
classic location of transitional
bladder
classic location of stratified squamous
skin
3 components of connective tissue
cells
fibres
ground substance
list the structure of connective tissue
-cells
-extracellular matrix: made of ground substance and fibres
what is ground substance made of?
gags
water
proteoglycans
what are types of fibres?
elastin
collagen
reticular
what is connective tissue?
diverse abundant supporting tissue
functions of connective tissue
structural support
tensile strength
binding
elasticity
immune response
cushioning
metabolism/energy store
what is connective tissue proper?
a type of connective tissue (the basic kind)
what are the types of connective tissue proper?
loose
dense
what is specialised connective tissue?
connective tissue that is specialised ie bone, cartilage, adipose, dentine, lymph
what are factors that effect ground substance?
hydration
balance of cells
what is a fibroblast?
the main type of cell in non-specialised connective tissue
what is the function of a fibroblast?
produce and maintain extracellular matrix and ground substance
activated myofibroblasts are involved in wound healing
what is the shape of a fibroblast?
spindle shaped, cigar shaped nucleus
what is fibrosis?
over activated fibroblast can ‘over heal’
what is a fibrocyte?
an inactivated fibroblast
what are the fixed cells in connective tissue?
fibroblast
fibrocyte
adipocyte
macrophages
why do adipocytes appear like a signet ring?
the stain washes away the lipid deposit in the centre so appears empty
ground substance function
viscous
bind high amount of water for hydration
diffusion of nutrients to tissue
what are the wandering cells that can move into connective tissue?
plasma cells
eosinophils
neutrophils
lymphocytes
mast cells
what is the appearance and function of plasma cells?
oval, clock face nucleus
actively produces antibodies
what is the appearance and function of eosinophils?
2 lobe nuclei
eosinophilic granules
appearance and function of neutrophils?
multi lobed nuclei
phagocytic functions
appearance of lymphocytes?
round nuclei
small cytoplasm
mast cells- appearance and function?
basophilic granules
inflammatory reactions
histamine production
histamine production what does it lead to?
causes capillaries to loosen
plasma leaves blood through gaps
into connective tissue
causes swelling (-oedema)
what does GAG stand for?
glycosaminoglycan
what are gags made up of?
often hyaluronic acid
contains glycoproteins and complex carbohydrates
have negative side chains
what are properties/functions of GAGs?
negative side chain: acidic and hydrophilic
strong
resistance to compressive forces
what are properties of elastin?
thin
branched
allows stretching
eosinophilic (pink)
how is elastin produced?
fibroblasts
secreted as a precursor- tropoelastin
polymerises to become elastin
required glycoprotein fibrillin scaffold
where is elastin found?
skin
ears
arteries
lungs
bladder
what is the most abundant protein in the body?
collagen
properties of collagen
high tensile strength
flexible but can break
eosinophilic (pink)
how is collagen produced?
fibroblasts
pre-pro-collagen
pro-collagen (triple alphas chain)
tropocollagen
types of collagen
type 1, 2, 3, 4
what is type 1 collagen?
bone skin tendons ligaments
what is type 2 collagen?
cartilage
what is type 3 collagen?
reticular fibres
what is type 4 collagen?
basement membrane
use of reticular fibres?
delicate and thin
forms framework of organs/glands/blood vessels
what does the basement membrane get stained with?
no H&E
PAS- periodic acid-schiff
what is loose connective tissue?
ie cells, proportions
equal amounts of cells, fibres and ground substance
cells: fibroblasts
fibres: often collagen, but also moderate amounts of others
function of loose connective tissue
binding tissues
diffusion
examples of loose connective tissue
lamina propria
mucous membranes
mesentery and dermis of skin
what is dense connective tissue?
fewer cells/ground substance
more fibres
types of dense ct
regular
irregular
dense regular tissue..
ie structure, function, examples
fibres run parallel to each other
high unidirectional resistance to stress
examples: tendons, ligaments
dense irregular ct…
ie structure, function, examples
interwoven fibres
3d network resistance in all directions
located: capsules/wall of organs, dermis of skin
white adipose tissue aka..
unilocular
white adipose tissue structure
single large lipid droplet
washed away with stain
most common in adult
function fo adipose tissue
storage
metabolism
fill spaces
padding
protection
insulate
energy reserve
brown adipose tissue aka…
multiocular
brown adipose structure
many smaller lipid droplets
common in newborn
or around kidneys/adrenals
rich in mitochrondria/capillaries
what is thermogenesis
use of glucose to produce heat
done by brown adipose
common in neonate
ehler danlos
type 1,3,5 collagen (genetic mutation)
fragile, extra elastic skin
hyper mobility of joints
marfans syndrome
fibrillin mutation (elastin scaffold)
affects tissue rich in elastin- aorta
skeletal defects- long digits/arms
which steps in glycolysis are irreversible?
1,3,10
regulation of metabolism is via which enzymes?
glycolysis- phosphofructokinase
gluconeogenesis- 1,6 bisphosphatase
at different levels of ATP what happens to the regulating enzymes?
low- phosphofructokinase and glycolysis is switched on
high- phosphofructokinase is switched off
1,6 bisphosphatase is switched on so ATP goes to glucose via gluconeogenesis
where does the TCA cycle take place?
mitochondrial matrix
oxygen’s role in metabolism
final electron acceptor
for NADH to lose electrons and NAD to return to the cycle
TCA starting component? end product?
pyruvate to CO2
carbon net through TCA cycle
add two carbon atoms (acetyl group) and release 2 (from oxaloacetate) as CO2
overal products in one turn of TCA
acetyl CoA -> CoA + 2CO2
3NAD+ -> 3NADH
FAD -> FADH2
GDP + Pi -> GTP
what are the hydrogen carriers
NAD+
FAD
NAD+ from where? and how many molecules of ATP does its oxidation generate?
vitamin niacin (B3)
2.5 molecules of ATP
FAD from where? and how many molecules of ATP does its oxidation generate?
vitamin riboflavin (B2)
1.5 molecules of ATP
how does FAD get oxidised?
attached covalently to its enzyme
succinate dehydrogenase contains FAD and is bound to the inner membrane of the mitochondria
anaplerotic reactions
reactions that fill in missing intermediates for important metabolic pathways
examples of anaplerotic reactions in the TCA cycles
pyruvate -> oxaloacetate
oxaloacetate <-> aspartate
glutamate <-> a-ketoglutarate
malate <-> pyruvate
overal of glycolysis and TCA cycle of hydrogen carriers
10 NADH
2FADH2
NADH oxidation
NADH + H+ -> NAD+ + 2H+ + 2e-
final electron acceptor equation
2e- +2H+ +1/2 O2 -> H20
the transport of 2 e- will pass how many H+ into the inner membrane?
4
how many hydrogen ions are required to make 1 ATP?
3
(plus 1 to translocate the ATP in the cystol)
what is the job of cytochrome c oxidase?
transfer electrons to oxygen
what can cytochrome c oxidase be inhibited by?
cyanide
carbonmonoxide
azide
what is substrate level phosphorylation?
transfer of phosphate from substrate to ATP
what is oxidative phosphorylation?
formation of ATP coupled to oxidation of NADH or FADH2 by O2
role of ATPsynthase
stop H+ being allowed to flow back and energy then lost as heat
drive synthesis of ATP via conformational change of ATPsynthase
the glycerol phosphate shuttle
why? how?
why? can only be oxidised inside the mitochondria but cannot cross the membrane
how? NADH to reduce DHAP to form glycol-3-phosphate
diffuses in
oxidised by glycol-3-phosphate dehydrogenase to from DHAP and FADH2
malate/aspartate shuttle mechanism
cystolic oxaloacetate
malate dehydrogenase reduces OAA to form malate
into mitochondria
reversed by malate dehydrogenase
transaminated to aspartate transported into cystol, back to OAA by aspartate aminotransferase
the glutamate aspartate carrier
maintains glutamate and aspartate cones
uses 1 h+
so less ATP per NADH
thermogenesis how?
through uncoupling proteins (UCP) provides proton channel
what type of protein is the drug dinitrophenol?
uncoupler
useful for thermogenesis
what can be used to make ATP?
date acids
proteins
lactate
glucose
etc
how to control metabolism?
enzyme levels
enzyme activity
substrate availability (eg GLUT)
GLUT?
glucose transporter
what is phosphofructokinase regulated by?
activated by AMP
activated by F-2,6-BP
inhibited by ATP and citrate
control points of the TCA cycle are inhibited by what?
eg. pyruvate dehydrogenase, isocitrate dehydrogenase, a-ketoglutarate dehydrogenase
ATP, NADH and acetyl CoA
metabolism profile of the brain
60% of body glucose consumption at rest
use ketone bodies in starvation
metabolism profile of muscles
uses fatty acids at rest
anaerobic muscle - glycogen stores
diabetes mellitus
imbalance of insulin and glucagon
high blood glucose
excessive ketone body production
warburg effect
coverts to lactate and TCA partly in aerobic conditions
due to a tumour
amoeba
unicellular organism
zygote
fertilised egg
what are the key cell processes?
cell division
cell death
cell differentiation
the stages of differentiation
maintenance (stem cell)
expansion (progenitors)
differentiation (differentiated cell)
pluripotent
can differentiate to any type of cell (stem cell)
multipotent
can different to multiple/not every type of cell (progenitors)
unipotent
can only be one type of cell
oligopotent
can form 2+ types of cells
why is cell differentiation so important?
the requirement for new cells is continuous and huge
what makes cells different from each other?
functional roles
proteins
-cell type features
-metabolic
-structural
-regulatory
platlets form…
haemostatic plug
DNA binding domsin is..
part of a protein where the DNA binds (promoter/enhancer)
activation domain is…
the part of a protein that interacts with RNA polymerase
enhancer vs promoter
enhancer- enhances transcription
promoter- initiates transcription
different transcription factors can control what?
differentiation of cells
what causes differentiation?
extracellular signs
or transcriptional factors
erythropoietin does..
promotes cell survival and differentiation
how does differentiation work?
bind to receptor
signalling cascade
causes genes to be switched on/off
RNA and DNA structure
DNA- double stranded, high molecular weight
RNA- single stranded, heterogeneous in size
nucleotide consists of…
phosphate sugar base
difference between ribose and deoxyribose
2nd carbon
DNA - h
RNA- oh
nucleotides are joined by…
phosphodiester linkages
in the 5’ -> 3’
why is RNA unstable?
the OH (in the ribose) can react with the phosphate
how are DNA bases paired?
direction, type
antiparallel, one 5’ to 3’, one 3’ to 5’
by hydrogen bonds
AT, GC
GC have stronger bond as three h bonds
chromosomes
single molecule of DNA
gene
sequence of DNA that contains genetic instructions
the human genome is diploid/haploid?
diploid
where is DNA found?
nucleus and mitochondria
how many genes are in the mitochondria?
37
inherited from mother
how many chromosomes are there?
23 pairs
exons are..
coding DNA, expressed
introns are…
non coding dna
where is the promoter region?
start
where is the enhancer region?
anywhere
several per gene
tandem repeats
repeated sequences
satellite DNA
large arrays of tandem repeats
eg certain repeats at centromeres
mini satellite
how many/function…
up to 100 copies in one block
found at telomeres
highly polymorphic
no known use
micro satellite
small arrays of simple repeats (eg CAG)
usually intronic
what’s the role of a telomere?
allow replication of tip of chromosome
protect end of chromosome
what the role of the centromere?
segregation during cell division
proteins can bind and recognise the sequence
what does microRNA Do?
bind to 3/UTR to inhibit translation
different types of RNA
rRNA
tRNA
snRNA
snoRNA
miRNA
mRNA
what is the unit of chromatin
nucleosome
what is an nucleosome
DNA wound round a histone core
what is beads on a string
chromatin
how are decondensed chromosome organised?
by attachment to nuclear skeleton
by functional role
nucleolus role
ribosomal RNA is transcribed and ribosomal subunits are assembled
euchromatin
paler
normally in gene rich areas
allowing access for transcription
is part of DNA in-between genes
heterochromatin
highly condensed/inactive
generally gene poor
not often transcribed
where can extension occur?
the 3’ end only
where is DNA replication initiated?
replication origins
opened with the aid of initiator proteins
what are dNTPs
building blocks for DNA synthesis/replication
Okazaki fragments
works in parts to work 5’ to 3’ (of new strand) direction
what binds Okazaki fragments together
DNA ligase
what is the lagging strand?
where the fragments take place as DNA polymerase must work backwards
what is the leading strand?
DNA polymerase can work continuously
why are are RNA primers used?
so that DNA polymerase can bind
how do RNA primers work with Okazaki fragments?
primer added
then once used replaced by DNA
why is there minimal mistakes in DNA replications?
stability of base pairing
proof reading by DNA polymerase
DNA polymerase requirements
template and RNA primers
dNTPs
how is a mutation rectified?
mismatch repair system
what is depurination?
losing a base
addition of water
what is deamination?
change from cytosine to uracil
what does UV do to thymine?
forms dimers so two bases join
functions of the skin
physical protection
thermoregulation
sensation
metabolic functions
indicator of health
what are the three main layers of skin?
epidermis
dermis
hyperdermis
what type of epithelium is the epidermis?
keratinised stratified squamous
what is the epidermis filled with?
mainly keratinocytes
what are the layers of the epidermis?
stratum corneum
[stratum lucidum - thick skin]
stratum granulosum
stratum spinosum
basal layer/stratum basale
stratum basale
cuboidal cells
most deep layer
on top of basement membrane
melanocytes present
stratum spinosum
8-10 cell layers
connected by desmosomes
prickly appearance when dehydrated
produces cytokeratin
stratum granulsum
3-5 cell layers
towards top are squamous
granules full of keratohyalin (deep stain)
keratin maturation steps
SB mitosis
SS cytokeratin
SG keratohyaline granules
SC keratin
stratum lucidum
only in thick skin
no hair
stratum corneum
mature keratin (cytokeratin+keratohyaline)
squamous
no cytoplasm or organelles
role of melanocytes
produce melanin in basal layer
UV protections
pigment
role of Merkel cells
in basal layer
associated with free nerve endings (sensory)
rolde od langerhans
immune
in all layers
other cells in epidermis
melanocytes
merkel cells
langerhans
what are the layers of the dermis?
papillary
reticular
papillary layer type
loose connective tissue
lots of gs and capillaries
reticular layer type
dense irregular collagenous tissue
elastin is present but reduces with age
neurovascular supply of dermis
subpapillary and cutaneous plexus with shunting vessels between
why are shunting vessels important?
control vasoconstriction
thermoregulation
controlled by ANS
what are the five types of mechanoreceptors in the skin
mostly in dermis
unencapsulated:
merkel
free nerve endings
encapsulated:
pacinian corpuscle (subcutaneous)
ruffini corpuscle
meissners corpuscle
what is hair made of?
keratin
how does hair get oily?
sebaceous glands secrete oily sebum on upper part of hair follicle
what do the arrector pili muscles do?
make hairs stand on end
where are sweat glands found?
superficial hypodermis
where are sebaceous glands?
attached to hair follicles
classes of exocrine glands based on their secretion
merocrine
apocrine
holocrine
two types of sweat glands
eccrine
apocrine
[both merocrine]
what is a merocrine gland?
release secretory products by exocytosis
mostly proteins
eccrine sweat gland
where?why?
directly on to skin
found everywhere
function = heat loss (ANS)
apocrine sweat gland
where? why?
open into hair follice
regulated by hormoes
limited to axilla/genitals/areola
smelly
psoriasis
abnormal epidermal growth
malignant melanoma
malignant growth of melocytes
vitiligo
autoimmune destruction of melanocytes
cause of atopic dermatitis
environment (hay fever)
cause of contact dermatitis
chemial (hairdressers)
cause of seborrheic dermatitis
sebum
superficial epidermal burn (layers/symptoms)
dermis intact, epidermis affected
skin red, painful, non blisters
partial thickness- superficial dermal burn (layers/symptoms)
epidermis and upper layer of dermis affected
skin pale pink and painful with blisters
partial thickness- deep dermal burn
(layers/symptoms)
epidermis and all layers of dermis affected
skin apperas dry/moist, blotchy and red
may be blisters
maybe painful
full thickness burn (layers/symptoms)
through all layers of subcutaneous tissue
dry and white/brown/black skin
no blisters
leathery/waxy
painless
autograft
own skin moved
allograft
donor skin used to reconstruct skin
what is the purpose of mitosis
cell division
growth
genetically identical products
kinetochore
protein assembly at centrosome for attachment of microtubules
different types of mitotic spindle
aster microtubules (all way round)
kinetochore microtubules (centromere)
interpolar microtubules (opposite poles to push apart)
prophase
chromosomes condense
centrosomes move apart
prometaphase
nuclear membrane breaks down
spindle microtubules attach to kinetochores and move actively
metaphase
chromosomes align at the equator of the spindle
kinetochores from paired sister chromatids attach to opposite poles of spindle (M PHASE CHECKPOINT)
anaphase
sister chromatids synchronously separate fast
kinetochore microtubules shorten
spindle poles move apart
telophase
chromosomes arrive at poles
nuclear envelope reassembles giving two new nuclei
nucleoli reappear (RNA synthesis begins)
initiation of plasma membrane cleavage
cytokinesis
contractile ring is formed and mediates division of cell into two
meiosis function
reduction division (becomes haploid)
reassortment of genes:
-independent segregation of chromosomes
-crossing over
mechanism of meiosis
each homologue replicates to give two chromatids
exchange of material between non sister chromatids
chiasmata
physical manifestations of crossing over
hold chromosomes together when crossing
leptotene
chromosomes are unpaired fine threads consisting of two tightly bound sister chromatids
zygotene
maternal and paternal homologs pair together to form bivalents
pachytene
chromosomes thicken
crossing over occurs
diplotene
homologs separate but are held together by chiasmata
crossovers can be counted and positions recorded
diakinesis
bivalents more contracted
stages of reassortment
leptotene
zygotene
pachytene
diplotene
diakinesis
meiotic metaphase 1
kinetochore microtubules of sister chromatids point in same direction
function as one unit
meiotic anaphase 1
non sister chromatids pulled apart
arms of sister chromatids become unglued
meiotic metaphase 2
kinetochore of sister chromatids point in different directions
meiotic anaphase 2
cohesins in centromere degraded
sister chromatids separate
which required more cell divisions? sperm or egg?
sperm
the cell divisions in an human egg produce…
polar bodies
to mainatin the amount of cytoplasm
what direction is RNA synthesised
5’ to 3’
ribosomes function
assemble strings of amino acids as instructed by mRNA
how many codons can a ribosomes read at a time?
2
tRNA structure
3 hairpin stem loop
polyribosome
multiple ribosomes can be reading one strand of mRNA
why is it important to define the start of the coding region?
it can shift the reading frame
the genetic code is…
read in groups of 3 bases
read in 5’ to 3’
3 possible reading frames
amino acids are coded by codons
degenerate
universal
mutation types
deletion
insertion
substitution/point mutation
epigenetics effects…
phenotype
what are genes composed of?
structural information for a protein
regulatory sequences to expression
general transcription factor mechanism
recognise and bind to gene promotor
recruit RNA polymerase
allow basal level transcription
rates of transcription are controlled by…
enhancers
gene-specific transcription factors
what signals from the environment interact with RNA polymerase
hormones
nutritional signals
environmental signals
nucleosome structure
8 histones
approx 200 bp
high numbers of arginine and lysine to neutralise negative DNA
histone tails can be modified by…
acetyl
methyl
(regulatory)
the histone code
a layer of information overlaying the DNA
involved in turning genes on or off
which enzymes families modify histone tails
histone acetyl transferases
histones de-acetylases
factors that effect histone acetylation
therapeutic drugs
environmental factors
cell metabolism
x-inactivation
random
occurs in inner cell mass of the blastocyst
passed onto cell generations
heritable epigenetic
radio-
image using radiation
graph/gram
an image
angio-
vessel
arterio-
artery
veno-
vein
salpingo-
Fallopian tubes
medium
different states of matter
attenuation
anything that decreases the amplitude of a sound wave
cholangio-
bile ducts
hystero-
uterus
arthero-
joints
cyst-
bladder
non-ionising imaging
ultrasound
mri
doppler
endoscopy
ionising imaging
x-rays
nuclear imaging
ct
X-rays mechanism
bombarding tungsten anode with electrons
dense tissues- lighter
soft tissues- darker
radiopaque
dense, white
radiolucent
soft, dark
posteroanterior projection
p to a
anteroposterior radiographs
a to p
contrast medium must be…
water soluble
non toxic
high density
contract medium is used for
differentiating soft tissues
usually barium salts
angiography uses…
iodine substances into blood
ct mechanism
narrow beam of xrays aimed at patient and quickly rotated around the body
allows for soft tissues to be viewed
often contrast medium needed for abdomen or chest
ultrasound mechanism
high frequency sound waves
travel through medium until hit one of a different consistency then echoed back
real time 2d image
bone reflects waves therefore white on uss
attenuation
loss of energy from the system
greater = less signals received
MRI mechanism
creates static magnetic field around patient
a secondary energy field is added perpendicular
this flips/rotates protons
secondary field then switched off
causes relaxation (return to original)
protons emit energy
is detected by machine and used to determine distribution
-no metal allowed
-contrast sometimes used
fMRI used for
determines blood flow through brains
endoscopy mechanism
via mouth
mucosa visualised
see gastric or duodenal ulcers
bronchoscopy
trachea and bronchi
nuclear imaging
most common radionuclides are technetium-99m (bones), iodine-123 (thyroid)
emit gamma rays which are detected
reflect function and morphology
emission computer tomography
moving detector nuclear imaging
radiography advantages
Bone and joint injuries shown clearly
Relatively cheap
Quick & portable
Patients relatively comfortable position
radiography disadvantages
Safe however use of radiation may not be suitable for some
Lack of detail on soft tissues
CT advantages
Better for soft tissue than conventional radiography
3D image
good clarity
CT disadvantages
More radiation used than x- rays so shouldn’t be done too frequently.
Contrast media needed for abdomen and chest study
Relatively expensive & loud
claustrophobic
USS advantages
Non-invasive
No harmful effects so can be used to evaluate growth & development of foetus
images viewed in real time
Good for soft tissue
Cheap & quick
Portable
USS disadvantages
Fat & gas cause poor image quality.
Skilled operator needed for good image
Restricted to superficial structures
MRI advantages
Good for tissue differentiation & soft tissue
No radiation
High resolution
non-invasive
No biological hazard
MRi disadvantages
Expensive
Cannot be used on those with pacemakers or metal implants (magnetic)
Loud and long scan
Claustrophobic
endoscopy advantages
real time
good detail
endoscopy disadvantages
invasive
nuclear advantages
can produce images that reflect function an morphology
Target particular tissues
nuclear disadvantages
High radiation involved may not be suitable for some
Can not be used too often
Invasive due to administration of radionuclides
intravenous anti peristaltic agents
minimise motion
delay clearing of contrast agent
interventional radiography
minimally invasive treatment/diagnosis using small incisions
What does the star protein regulate?
Hint-steroid hormone synthesis
Movement of cholesterol into the mitochondria
Where it is converted to pregnenolone
What regulates star activity?
ACTH via cAMP