cell biology Flashcards
what do cell membrane do
Maintain differences between the cytosol and extracellular environment
what does the cell membrane do
Provides attachment sites
Functions in cell signalling
What does amphiphilic moelcules mean
regions of both hydrophobic and hydrophilic
n
what type of bond do hydrophobic tails contain
have a cis double bond
how does the cis double bond affect membrane fluidity and width
The cis double bond makes chains more difficult to pack , hydrocarbon chains are more spread out and lipid bilayers are thinner
whta do phosphilids do at low temp
due to reduced energy they move less and pack together tighter
what do saturated hydrocarbons allow for
closer packing
At low temp how does cholesterol affect fluidity in cell membrane
cholesterol increases the spacing between the hydrocarbons and increases fluidity
At high temp how does cholesterol affect fluidity in cell membrane
cholesterol pulls the hydrocarbon tails together and decreases fluidity
what is flip flopping in the cell membrane
movement of a lipid / protein from one side of a cell membrane to another
how do lipid fats form
this occurs from membrane enriched in cholesterol and sphingolipids that form rafts and move laterally
what is NLS - Nucleaur Localisation Signal
Amino acid sequence tha tags a protein for entry into the nucleus
What is the Nuclear Export Signal
Amino acid sequence that tags a protein for exit from the nucleus
what does the nucleur pore complex do
Regulates movement in/out of nucleus
why is the function of the nucleur pore complex so important
allows small moelcules to repaidly move freely in and out
larger proteins move more slowly
how does the co-translational protein import into the ER occur
-ribosome binds to ER membrane
-Protein imported into ER
-Requires ER signal sequence
-Transloctaor closed until ribosome binds
-N-terminal signal peptide iniates passage of protein through translocator
-signal peptide cleaved by signal peptidase
what is a polysome
group of ribosomes that are attached to a strand of mRNA and work together to translate the mRNA into protein
whats an oligosaccharide
carbohydrate made up of a small number of simple sugars
How do vesicles move from the ER to the Golgi
-Vesicles bud off the ER at specialised exit sites with a COPII coat
-COPII plays a role in recruiting proteins with “exit or transport “ signals
-Incorrectly folded proteins retained in the ER
how do vesicles get from the ER to the cis Golgi
Vesicles move from the endoplasmic reticulum (ER) to the cis-Golgi by budding off from the ER membrane and fusing with the cis-Golgi membrane. This process is called vesicular transport
what is the cis golgi
a large network of tubules and vesicles that is part of the Golgi apparatus and receives and processes proteins and lipids from the endoplasmic reticulum
what are the 2 routes that vesicles can take to get from the ER to the Golgi
cisternal maturation
vesicle transport
what is the cystosol
The aqueous portion of the cytoplasm
What do mitochondria do
highly fodled so increase SA
move in straight lines
can bind into the microtubules via the mito protein
what is the strucuture of mitochondrion
Porins - allow small molecules through
Outer membrane-Includes porins , membrane channels permeable to molecules 5KDa or less
Intermembrane space-Similar composition to cytoplasm for smaller molecules
Inner membrane-Cristae , includes an unusual double phospholipid Cardiolipin(different lipid composition - cardiolipin - has 4 tails instead of the usual 2 )-Function - makes membrane impermeable to ions
Electron transport chain - series of proteins embedded in the membrane which allow transport of protons across the membrane
ATP synthase - embedded , allow production of ATP
Matric - space enclosed by cristae
Mitochondrial DNA - usually circular
what are the two parts of mitochondrial fission
Midzone fission
Peripheral fission
what happens in midzone fission
Mitochondria breaks into two
what happens in peripheral fission
1)Pinching of end region
2)All material packed into one end of mitochondrion
3)This end is pinched off and gets rid of the material which isnt useful
what can peripheral fission be used for
To get rid of damaged material
what happens during stage 1 of the chemiosmotic coupling
(E=electrons)
-E trasnffered along series of E carriers embedded in membrane
-This releases energy used to pump H+ across membrane
-Protein gradient by moving protons across inner mitochondrial membrane
-Oxides NADPH
-2 electrons reduce oxygen to water
what happens during stage 2 of chemiosmotic coupling
-Fats broken down releasing high energy electrons
-This is broken down by the citric acid cycle , releasing electrons
-2 electrons picked up by NAD+ creating NADH
-Glycolysis converts glucose to pyruvate
Features of prokaryotic ribosomes
-70s ribosomes
-50s large subunit
-30s small subunit
Features of eukaryotic ribosomes
-80s ribosomes
-60s large subunit
-40s small subunit
What are the three domains on the ribosomes
E site
P site
A site
what do the sites on the ribosomes do
A site=incoming aminoacyl tRNA( binding site where amino acids are brought in )
P site =binding site that holds tRNA
E site = Exit of deacylated tRNA
What are RIPS
Ribosome inactivating proteins
How does peroxisome biogenesis and maturation occur
-Budding of vesicles from the ER
-Import proteins recruit peroxisome proteins
-Peroxisomes undergo fission to replicate
what hydrolytic enzymes do lysosomes contain
proteases,nucleases,phospholipases
what is autophagy
Process that occurs in cells to break down
Why does the lysosome not digest itself
-Modified lipid membrane with highly glycosylated proteins
-Membrane transporters to remove and recycle / extract digestion products
-Vacuolar H+ ATPase - hydrolyzes ATP and pumps protons into the lysosome
what are proteasomes
protein complexes that break down proteins in cells
What are proteasomes important for
Important for degredation in the cell , to only make the correctly folded functional proteins
What are the functions of the cytoskeleton
-Gives the cell its shape
-Capacity to move or alter its shape
-Organisation of organelles
-Transport of organelles
What are the components of the cytoskeleton
-Microfilaments
-Intermediate filaments
-Microtubules
What are microfilaments comprised of
Comrpised of a linear assemblies of 43kDa actin protein monomers
What do actin filaments consist of
Consist of 2 strands of F-actin
What are ends of the microfilament called
It is polar with a “barbed”- the plus end and “pointed”the minus end
What modulates the rate of microfilament synthesis
Profilin and thymosin levels
What does profilin do in terms of actin
-Competes with thymosin for binding to actin monomors
-Binds to actin subunit , making it more available for binding
-Thymosin causes no binding
Whta does a -Tublin have that b-Tublin doesnt
Has a bound molecule of GTP
what is the major Microtubule Organising Centre of animal cells
The centrosome
What can microfilaments do
Can polymerise and deploymerise
How does the regualtion of microfilament length occur
-CA2+ dependent binding of gelsolin can cause cleavage of the microfilament
-The gelsolin / microfilament complex can act as a primer for chain elongation
-Gelsolin is freed by PIPZ producing free positive ends for rapid microfilament elongation
What do Microtubule associated proteins do
They allow crosslinking of microtubules
What end of the microtubule does the motor protein Kinesin move towards
The plus end
What end does Dynein (a motor protein)move towards on the microtubule
The minus end
How many binding regions does myosin have
2
characteristics of motor proteins
Globular head region-engages the filament and actively moves along it
Tail region-Point of attachment of the motor protein and its cargo
Power stroke-ATP hydrolysis causes a conformational change thrusting the head backwards creating tension in the tail
This moves the tail and cargo forward
characteristics of kinesin
Dimer of a heavy and light chain
Forms a tetrameric structure
Three domains:
1-Large globular head
Binds microtubules and ATP
2-Stalk
3-Small globular head
Binds to vesicles
what is kinesin
a motor protein that moves along microtubules in eukaryotic cells to transport cellular cargo
How does a cilium move
-Primary force is an ATP-driven ciliac movement of ciliary dynein
-Dynein movements cause MTs in cilium core to slide against each other
-Causes cilium to bend
Whats the difference between power stroke and recovery stroke of a cilia
The power stroke is the active, force-generating phase of ciliary movement
The recovery stroke is the reset phase that occurs after the power stroke.
What is the cytoskeleton important for
The cytoskeleton is important to have an accurate partitioning of the chromosomes during division(important in anaphase)
How do actin and the membrane interact
-Interaction between actin and the membrane is indirect via specific groups of actin binding sites
-Around 100 actin binding proteins have been described
what are three examples of actin binding proteins and what do they do
Type1-ABPs that bind to the membrane via interaction with lipids
Type2-Integral membrane proteins
Type3-ABPs that associate with an integral membrane protein
How does Duchenne muscular dystrophy (GMD) occur?
Mutations in dystrophin
What is chromatin
complex of DNA and proteins(histones) and non-histone proteins
what does Peroxisome Biogenesis and Maturation mean
Peroxisome Biogenesis and Maturation refer to the processes by which peroxisomes, essential organelles within cells, are formed and developed to carry out their vital functions
How does a cilium move
-Primary force is an ATP-driven cycli movement of ciliary dyein
-Dynein movements cause MTs in cilium core to slide against each other
-Causes cilium to bend
What two functional domains do each of the core histones from the octomer possess
amino - terminal tail and histone fold
whats a dimer
dimer is a molecule composed of two identical or similar subunits, known as monomers, that are chemically bonded together
whats a histone octamer
A histone octamer is a structural complex composed of eight histone proteins that play a key role in organizing and packaging DNA into a compact structure called chromatin in eukaryotic cells
Histone octamer is formed from what dimers
H3-H4 and H2A-H2B
what do linker histones do
bind both DNA and nucleosome core. They can change the path of DNA that exits nucleosome. Hence, it affects the linker DNA accessibility, organisation of higher order chromatin fibre and chromatin compaction
What two kind of complexes form from proteins from the (SMC) structural maintenance of chromosomes
Cohesion and condensin
what stage of the cell cycle is chromatin organised into loops
Interphase
what are loop domains organised by
Organised by Cohesin complexes and CTCF protein
Is mitotic chromatin organised into loops
Yes
What happens to cohesion and condensin in prophase
Cohesion is removed and condensin is used more which form loops randomly
what is the definiftion of interphase
Interphase-the period between the end of one M phase and the beginning of the next
what occurs during M phase in the cell cycle
M phase: the cell - cycle phase during which the duplicated chromosomes are segregated and packaged into daughter nuclei (mitosis) and distributed into daughter cells (cytokensis)
what is chromatin
Chromatin: complex of DNA , histones , and non-histone proteins found in the nucleus of a eukaryotic cell
what are histones
Histones : a group of small abundant proteins , rich in basic amino acids , that combine to form the nucleosomes cores around which DNA is wrapped in eukaryotic chromosomes
Where are the three checkpoints in mitosis
-G1 checkpoint (start transition)
-G2 checkpoint (G2/M transition)
-Metaphase checkpoint( metaphase to anaphase transition)
what is cyclin
Cyclin is a type of regulatory protein that plays a crucial role in controlling the progression of the cell cycle. Cyclins bind to and activate cyclin-dependent kinases (CDKs), forming complexes that drive the cell through different stages of the cell cycle.
is Cdk active or inactive with cyclin
active
What do G1 clyclins do ( in mitosis- at the start )
Cyclins that bind and activate Cdks that stimulate entry into a new cell cycle at start:their concentration depends on the rate of cell growth or on growth-promoting signals rather than on the phase of the cell cycle
What do cyclins do
Bind to different Cdks
what regulates Cdks -cyclin depdendent kinase
CAKS- cyclin activating kinases
What are CAKs responsible for
Cdk-activating kinases (CAKs) are responsible for fully activating the cyclin-CDK complexes.
How does CAK activate Cdk
-Cyclin binds to inactive Cdk
-The T loop then moves out of the active site
-Phosphorylation of the T loop causes the Cdk to become now fully active as the shape of the T loop has now changed
How does the wee1-Cdc25 regulatory pathway work in order to control the Cdk activity
-Phosphorylation inactives the cyclin-Cdk complex whilst dephosphorylation by the phosphate Cdc25 leads to reactivation
How do Cdk inhibitor proteins inactivate cyclin-Cdk complexes
-CKI ( CDk inhibiting proteins) binds to the Cdk , changing the structure of it so that it becomes inactive
-CKI is a protein that interacts with Cdks/Cdk-cyclin complexes to block their activity
What are the three control mechanisms for the cell cycle
signalling pathways
transcriptional regulation
regulated proteolysis
whats a polyubiquitin chain
Polyubiquitination: The addition of multiple ubiquitin molecules to a protein results in a polyubiquitin chain, which serves as a signal for recognition by the proteasome.
what is the proteasome responsible for
Proteasome is a large protein complex with proteolytic activity that is responsible for degrading proteins marked by polyubiquitin modification
How are proteins digested by the proteasome
-The polyubiquitin chain is translocated into the proteasome core , where its digested
-This is cleaved from the susbtrate protein and recycled
What is APC/C
Anapahase promoting complex / cyclosome
What does APC/C do
The APC/C is a highly regulated E3 ligase complex that plays a pivotal role in the regulation of the cell cycle, particularly during anaphase and metaphase-to-anaphase transition. It targets proteins for degradation that regulate mitosis, ensuring proper chromosome segregation and progression through the cell cycle.
what do Cdc20 and Cdh1 activate
APC/C complex
What do Skp2,FBW7,B-TRCP activate
SCF
What is metamaphse to anaphase transition driven by
Anaphase promoting complex (APC/C)
What four stages does the cell cycle consist of
G1-S-G2-M
What are the regulatory mechanisms that control the Cyclin-Cdk complex activity
CAK-activating kinase (stimulation by activating phosphoroylation)
Wee1(Supression by inhibiting phosphoroylation)
CKIs(Supression by binding of Cdk inhibitor roetin)
what occurs during prophase
-replicated chromosomes condense
-Mitotic spindle assembles between the two centrosomes , which have replicated and moved apart
-Longest phase
what occurs during prometaphase
-Breakdown of nuclear envelope
-After nuclear envelope breakdown(NEBD) chromosomes can attach to spindle microtubules via their kinetochores and undergo active movement
–Open mitosis
What occurs during metaphase
-Chromosomes are aligned at the equator , midway between the spindle fibres (metaphase plate).The kinetochore microtubules attach sister chromatids to opposite poles of the spindle
What are chromosomes attached to the mitotic spindle via
Kinetchores
where are kinetochores assembled on
Assembled on the centromeric chromatin (the centromere)
what are kinetochores responsible for
The attachment of microtubules
what holds the sister chromatids together in mitosis
held together by cohesion
What leads to the activation of the Spindle Assembly Checkpoint
Lack of proper connection between a kinetochore and microtubule fibre leads to the activation of the Spindle Assembly Checkpoint
which leads to the inhibition of APC/C
What does inhibition of APC/C do
Inhibited APC/C stops the progression of mitosis in metaphase
What does the spindle assembly checkpoint do
Spindle assembly checkpoint
1-Detects incorrect attachments at kinetochores
2-Arrests cells in metaphase
3-Provides more time to correct improper attachments
What keeps APC/C inactive
spindle assembly checkpoint(SAC)
what is Ubiquitination
Ubiquitination is the process of attaching a small protein called ubiquitin to a target protein
What two major functions does APC/C do when activated
-Ubiquitination of securin
-Ubiquitination of Cyclin B
What does Ubiquitination of securin do
-seperase removes cohesion from centromers which triggers anapahase
what does securin inhibit
Securin inhibits separase, preventing chromosome separation
What does the APC/C do to securin
The APC/C complex, activated by Cdc20, ubiquitinates securin, marking it for degradation.
What does seperase do in the cell cycle that allows sister chromatids to seperate
Separase cleaves cohesin, allowing sister chromatids to separate and move toward opposite poles, leading to successful anaphase.
What occurs in anaphase
-The sister chromatids synchronously separate to form two daughter chromosomes
-Shortening of kinetochore microtubule and the spindle poles move apart
what occurs in telophase
-Chromosome decondense
-Nuclear envelope reasembles around chromosome masses
-Microtubules that start to form central spindle
-Contractile ring (composed of actin) start to contract
What occurs in cytokinesis
-Cytoplasm divided in two by a contractile ring of actin and myosin filaments , which pinches the cell in two to create two daughter cells
What is the centrosome responsible for
The production of microtubules
What do microtubules form in mitosis
Form mitotic spindles
Is alpha or beta tubulin exposed on the minus end of a microtubule
alpha
What allows for the controlled entry into mitosis
accumulation of M-cyclins and regulatory phosphoroylations of Cdk1
why does activated SAC ( spindle assembly checkpoint) inhibit the onset of anaphase
Inhibits the anaphase onset until all kinetochores are properly connected to microtubules
What do proper attachments of kinetochores trigger
-Inactivation of SAC
-Activation of APC/C
What two activites does APC/C induce
-Destruction of M-cyclins
-Activation of separase , which removes centromeric cohesin
How do tumours form
From the proliferation of cells
What is apoptosis
Programmed cell death
What do mitogens do
stimulate cell division
How do mitogens stimulate cell division
Mitogens,which stimulate cell division , primarily by triggering a wave of G1/S-Cdk activity that relieves intracellular negative controls that otherwise block progress through the cell cycle
What does a mutant receptor do
-Oncogenes encode mutant receptors whos tryosine kinase is permantly activated , missing its growth factor so growth factor cant bind
What are oncogenes
Oncogene; a gene whose protein product promotes cancer, generally because mutations or rearrangements in a normal gene (the proto-oncogene) have resulted in a protein that is overactive or overproduced.
What are tumour suppressor genes
Tumour suppressor gene; a gene that encodes a protein that normally restrains cell proliferation such that loss of the gene increases the likelihood of cancer formation
Why can cancer occur due to mutated p53 (hint-resulting in no cell death)
DNA damage , cell cycle abnormalities , but due to mutated p53 the cell cycle continues resulting in cancerous cells
what occurs in meisis1
-in mitosis homologous chromosomes remain separate.in meiosis homologous chromosomes recognise each other and associate physically
What are the homologs (in meiosis) joined by
Joined by a protein complex called the Synaptonemal complex (SC)
What is homolog synapsis (In meiosis I, specifically during prophase I, homologous chromosomes undergo a critical process called synapsis)
homologous chromosomes pair up with their homologs followed by a desynapsis , where they begin to seperate
what are the stages prophase 1 of meosis
Leptotene
Zygotene
Pachytene
Diplotene
What does SC stand for in meosis
Synaptonemal complex (SC)
what does the Sc - synaptonemal complex - do for chromosomes
Holds them together
what is a chiasma
A chiasma (plural: chiasmata) refers to a point where two homologous chromosomes exchange genetic material during a process called crossing over
are haploid or diploid gametes produced during meiosis
haploid
what occurs in prophase in meiosis
Meiosis 1 has a very long prophase , during which homologous chromosomes pair, synaptonemal complex forms to hold them together
what are plastids
Meiosis 1 has a very long prophase , during which homologous chromosomes pair, synaptonemal complex forms to hold them together
what are the features of a plastid
-enclosed by an envelope-a pair of membranes
-usually have an internal membrane structure
-Contain a reduced genome of a single circular chromosome of couple (have their own genome)
-stranded DNA
-Retain capacity for protein synthesis with translation using prokaryotic-like ribosomes
-Reproduce by division
The evolution of plastids
-range in size
-in chloroplast genes are organised in polycistronic transcriptional units
How are chloroplasts synthesised and transported
Chloroplasts are synthesized in the cytoplasm by ribosomes and then transported into the chloroplast.
what is photosystem 2
An enzyme used to split water
what does photosystem 2 contain that allows light to be absorbed
A light harvesting antenna
How does the light harvesting antenna in photosystem 2 absorb light
contains lots of chlorophyll and proteins
-It then transfers the energy to the reaction centre in photosystem 2
-Contains lots of pigemnts so increases range of wavelengths for light absorption
In the light harvesting antenna complex what are chlorophyll molecules held in place by
-Chlorophyl molecules are held in place by proteins called light harvesting- chlorophylla/b-binding proteins that span the thylakoid membrane
-carotenoids good at absorbing light , transfer this energy to the reaction centre
How do the electrons from PS2 get transported to PS1
-Pheophytin(modofied chlorophyll) accepts the electrons
- plastoquinone holds the electron and passes it on the cytochrome b6f complex , passes its electron to plastocyanin (in the lumen)
-Plastocyanin passes its electron to photosystem 1
-They then go to ferredoxin which then gets passed to ferredoxin-NADP reductase
-Which is where NADP+ is reduced into NADPH
How is ATP produced in the light dependent reaction (page 61)
-Membrane impermeable to protons generating the proton gradient
-High Ph in the lumen
-Low Ph outside the lumen allows for more protons
-ATP synthase enzyme takes the protons and passes them though the membrane, generating ATP
What occurs in the calvin cycle
Phase1-carbon fixation
phase2=reduction
phase3=regeneration of RuBP
1 molecule of glyceraldehyde 3-phosphate requires 9ATP and 6NAPDH
1 NADPH=Move 5 protons
Rubisco
Converts ribulose 1,5 bisphosphate to 3-phosphoglycerate
Regeneration of ribulose 1,5 bisphosphate
-Requires ATP
Glyceraldehyde-phosphate is transpired to the cytosol to make sucrose (glucose+fructose)
What is the problem with rubisco (hint-problem with recycling the cabron )
-When rubisco uses oxygen instead of carbon dioxide it is energetically costly to recycle the carbon
-When its warm , the stomata need to be closed to prevent water loss and this reduces gas exchange and the availability of c02, rubisco activity increases but affinity for c02 decreases and therefore more oxygen is used
C4 photosyntheiss is a solution to rubisco (increase co2) , how
C4 photosynthesis - the light and carbon reactions take place in specialised cells
In C4 plants , bundle sheath cells are photosynthetic and surrounded by layers of mesophyll layers
-Artificially create conditions where u have high co2 concentration around the rubisco
-Fix c02 differently , fixed as oxaloacetate
-The enzyme phosphoenolpyruvate (PEP) carboxylase fixes c02 as HCO3 to give oxaloacetate
-When c02 is limiting C4 plants can outcompete and photosynthesise more than C3 plants
CAM(Crassulacean Acid Metbaolism is used rather rubisco , how
-Adaptation to even more dry , arid conditions and the need to prevent water loss
In c4 plants there is a spatial separation (one cell doing the light reaction and another doing the carbon reaction- c02 fixation) of c02 fixation
-C02 is taken up at night and stored as malic acid in the vacuole until the light period , allow them to only open stomata at night to prevent water loss
-In the day c02 is available for fixation via the calvin cycle even with stomata closed
(in chloroplast malic acid converted to malate into C02)
What two things are needed for biochemical signalling
-Receptor and ligand
what is a ligand
-A signal ligand is a small molecule that forms a complex with a macromolecule typically a receptor protein , that results in a conformational change in the receptor and then generates a signal
what is a ligand
A ligand is a molecule or ion that binds to a specific site on a target protein or other macromolecule, typically through non-covalent interactions such as hydrogen bonds, ionic bonds, or van der Waals forces. Ligands can be various types of molecules, including small ions, gases, peptides, or even larger molecules like hormones or neurotransmitters.
what are contact dependent signals
Signals that target adjacent touching cells (need contact)
What are cell matrix signals
Signals from the insoluble extracellular matrix
What is involved with contact dependent signals
-Require interaction between membrane molecules on two cells, cells must be touching
-Signals are transmitted through cell membranes via protein components integral to the membrane of the emitting cells
-change in target cell
-Needs contact
what are three signals that are soluble
-Autocrine
-Paracrine
-Endocrine
How do autocrine signals work
-Autocrine signals are secreted and affect the target cell itself via its own receptor
-Releasing extracellular signal , binds ligand and causes a response
-cell that produces the signal has the receptor for that molecule
-Target site on same cell
what occurs in intacrine signalling (inta=in cell )
-Intracrine signals - produced by and stay within target cells
-receptor for that ligand is within the cell (intracellularly)
-Steroid hormones have their receptors in the cell so can act as intracrine
a signaling molecule, typically a hormone or other ligand, is produced within the cell and acts inside the same cell without being released into the extracellular space.
what occurs in paracrine signalling (neurotransmitters)
-Paracrine signals target cells in the vicinity of the emitting cell
-Very localised - eg neurotransmitters
-Target cell sits within the vicinity , but doesnt have to be in contact with it
What occurs in endocrine signalling
-Endocrine signals target distant cells by producing hormones that travel through the circulation to reach all parts of the body
-only going to bring a response if the cell has the correct receptor
-hormones have a low Kd ,hormone receptors are part of amplification cascades
-Only a few receptors are bound to the ligand
-Need to amplify signal to get a response
(page 64)
Where are the receptors for hydrophilic moelcules)
Have to sit on the outside of the membrane
Cant cross the plasma membrane so receptors at the cell surface
page 65
Where are the receptors for thyrodi hormones (inside or outside cell)
are hydrophobic but have a carrier at the cell surface to bring the ligand into the cell and have receptors in the cytoplasm
How is signal transduction defined
Defined as :How chemical or physical signals are transmitted through a cell as a series of molecular events
what is a ligand in simple form
In simple terms, a ligand is a molecule or ion that binds to a specific site on a protein or receptor to trigger a response. Think of it like a key that fits into a lock to activate or change something in a cell.
what do first messengers do in the signalling pathway
In a signaling pathway, first messengers are the signals or molecules that initiate the pathway by binding to a receptor on the cell’s surface or inside the cell. These messengers are typically extracellular (outside the cell) and include molecules like hormones, neurotransmitters, growth factors, or environmental signals.
do cell surface receptors need second messengers
yes
Ways to turn off singals in signalling pathways
-Enzymatic breakdown-cleavage of signal molecule to inactive components(acetylcholinesterase breaking down acetylcholine)
-Reuptake(Many neurotransmitters transferred back into the secreting cell)
In lipophilic signalling (hydrophobic) where are the receptors
inside the cell
How does nitric oxide signalling occur
-The target for Nitric Oxide is called Guanylate Cyclase , nitric oxide binds to the active site of this and activates it
-This leads to an increase in the production of cyclic GMP (cGMP) from GTP.
-The cGMP produced acts as a secondary messenger + causes relxation
-The effects of NO are temporary. Phosphodiesterase enzymes break down cGMP, thus terminating the signal and returning the cell to its normal state
-Phosphoroylated enzymes converted back to original form by phosphatases
What are the three forms of NO synthase
eNOS-blood vessel endothelial cells
nNOS-neuronal cells
iNOS-inducible isoform occurring in cells of the immune system
How does steroid signalling occur
-cant be stored in vesicles so released into blood
(bind to protein so helps being carried in blood )
-Readily diffuse into cells where they bind to cytoplasmic receptors
-Binding to their receptor unmasks DNA binding sites and nuclear localisation sites on the receptor
Transported to the nucleus as complex where DNA binding by receptor regulates gene expression
-Signal removed by metabolism of the steroid
Do thyroid hormones cross the cell membrane or diffuse into the cell membrane
-Thyroid hormones cant cross the cell membrane but have transporters to bing them into the cell
-They diffuse into nucleus
-Their receptors are already in the nucleus and bind
As steroid and thryoxine hormones are already in the cytoplasm what type of messenger dont they need
Secondary
What are the three classes of receptors for the hydrophilic signals
-Ligand-gated ion channels
-G protein-linked receptors
-Enzyme-linked receptors
Nicotinic Acetylcholine receptor is an example of what type of receptor(-Ligand-gated ion channels or
-G protein-linked receptors or
-Enzyme-linked receptors
)
-Ligand gated ion channel
what is the structure of a nicotine acetylcholine receptor
Structure:5 polypeptides(5 subunits)
-4 alpha helices ,
3 (M1,M3,M4) of these sit within the lipid membrane (they are hydrophobic)
M2 is amphiphilic so lines the pore , this acts as the channel
-The 5 amphipathic helices produce a channel across the membrane
-The alpha subunits have the acetylcholine binding regions
-Conformation changes on binding on binding of 2 acetylcholine molecules
how does acetylcholine binding occur (page 69)
-Acetylcholine binding causes the helices to rotate pulling charged residues from the pore opening it
-When closed the L faces inwards so there are no gaps
-When Ach bind they rotate and point outwards to allow molecules to enter,allow cations to enter
-It is non-selective but it permeable for Na and K
-Blocks larger + negatively charged ions
-Opening sodium channels will depolarise the cell as the membrane potential and sodium gradient result in sodium entering the cell
what is the structure of a G-protein linked receptor
-All have a 7 pass structure-cross the membrane 7 times
-N to C terminus
what is the mechanism for the activation of GPCR (G protein linked receptors)
-When a ligand binds to a GPCR it causes a conformational chain in the receptor
-Activation of G-protein: The conformational change activates the associated G-protein, which is composed of three subunits: α, β, and γ.
The α-subunit exchanges GDP for GTP, becoming active.
The βγ-dimer can also initiate signaling pathways.
Signal transduction: Activated G-proteins then regulate various intracellular signaling pathways by activating or inhibiting enzymes, ion channels, or other proteins
–When GTP bound an active signalling complex is formed , when converted to GDP it is inactive
-The large G proteins link to the inner plasma membrane and associate with receptors
-In the inactive state , the GPCR is bound to a heterotrimeric G protein complex
-Binding of a ligand at the surface of the GPCR results in a conformational change in the receptor that is transmitted to the bound Galpha subunit
-This causes the Galpha subunit to release GDP and exchange it for GTP
-This triggers the dissociation of Galpa subunit from the dimer and from the receptor
How many signalling proteins do G proteins dissociate into when activated
2
What are the targets of the actiated Gas (gamma alpha stimulation) subunit (hint-kinase)
-In case of the B-adrenergic receptor the alpha subunit of the activated G protein activates Adenylyl Cyclase
Adenylate Cyclase converts ATP to the second messenger cyclic AMP(cAMP)
-cAMP activates a protein kinase called Protein Kinase A (PKA)
-cAMP binds to the regulatory subunits of protein kinase A releasing the active catalytic subunits
What are the targets of the activated Gai (gamma alpha inhibitory) (hint-second messenger response)
-The alpha subunit inactivates the membrane bound enzyme andeyl cyclase
-Reduces second messenger cAMP
-Protein kinase A inactivated
how does calcluim act as an intracellular messenger
-Calcium binds to the protein calmodulin
-Calcium activated calmodulin activates calmodulin dependent kinase
-CaM kinase regulates the activity of many proteins
with juxtacrine signalling is it cell to cell contact
yes , cell to cell contact at the plasma membrane, cells must intercat with each other
what are the three types of specialized junctions
occluding junctions
anchoring junctions
communicating junctions
what are the features of communicating junctions (how does it work)-page 75
-form little pores between cells , calcium potassium and sodium can move through these cells
-Pore is regulatable
-Linked by gap junction
-Made from proteins called connexons
-Channels are regulatable so can close and open channels
- electrochemical signalling
-Gap junctions are regulated (eg the channels close at high ca+ concentrations allowing regulation of the coupling cells)
what is the role of communicating junctions
Role: Facilitate direct communication between adjacent cells, allowing the transfer of ions, small molecules, and electrical signals.
what is the role of occluding junctions
Role: Create barriers that regulate the passage of ions, solutes, and water between adjacent cells, helping to maintain tissue polarity and integrity.
what do tight junctions do (theyre a form of occluding junctions)
Tight Junctions (in vertebrates): Form a seal between adjacent epithelial cells, preventing the leakage of substances between cells. Tight junctions are critical for the regulation of paracellular transport and maintaining the compartmentalization of different tissue regions.
what do tight junctions result in
-Tight junctions result in a separation of a lumen about an epithelium
-Tight junctions compartmentalise the membrane as well as the surrounding cells,(cells have two separate surfaces)
-Produce impermeable bonds between cells limits paracellular permeability , maintains an osmotic variance across epithelia
-Built by two transmembrane proteins , both self interact
Have the claudins and the occludins
-Act as centres on the inner surface , form bands at the apex of epithelial cells , to interact to form an impermeable cells , also to act as a signalling cell
-Failure in tight junctions:Auto immune disease
what is the role of anchoring junctions
Role: Provide mechanical stability and structural support by connecting cells to one another and to the extracellular matrix. They also help maintain tissue integrity during mechanical stress.
what are the two types of anchoring junctions
adheren junctions
desmosomes
what are cadherins
Cadherins : calcium dependent adherence molecules of cell-cell anchoring junctions
Meaning their functions is regulated by the presence of calcuim ions
are cadherens calcuim dependent
yes
what is homophilic interactions
Homophilic interactions refer to the binding of similar or identical molecules between adjacent cells. These interactions are crucial for maintaining cellular adhesion and tissue organization. In the context of cadherins, homophilic interactions occur when cadherins on one cell bind to cadherins on an adjacent cell of the same type.
what is notch
a signalling pathway
what are lectins
proteins that bind to a sugar
what are the roles of the extracellular matrix
-Scaffold for tissue support , tensile and compressive strength
-Integrates cells into a tissue
-Limits a tissue by setting boundaries
-Signals information to cells about their surroundings
what three protein groups does the extracellular matrix contain
-Structural proteins(collagen,elastin)
-Proteoglycans(proteins but they have long chains of sugars on them which are important for how they behave)
3-cell adhesive proteins(which can link the structural and proteoglycans to the cell themselves , they have receptors -fibronectin,laminin
what is the role of collagens
collagens are the primary structural proteins responsible for providing tensile strength to tissues
how do collagen fibrils form (page 81)
-secretory pathway
–non collagenous parts are cleaved away whcih allows mature collagen trimer to be laid down into a fibril
What are MMPs (Matrix metalloproteinases)
Matrix Metalloproteinases (MMPs) are a group of enzymes that play a critical role in the regulated breakdown of the extracellular matrix (ECM), including collagen and other matrix proteins
characteristics of elastin
-Elastic fibres formed of the polymer elastin laid around microfilaments of fibrillin
-These molecules are cross linked to each other by hydroxylysine linkages
-Elastin is highly hydrophobic , giving random coils - hence it gives behaviour (stretching and relaxing), no defined structure
-Elastin synthesis in foetus and childhood
-Elastase is secreted by neutrophils , destroyed elastin isnt replaced after inflammation resulting in collagen being laid down more and end up in scarring and the elasticity is lost over time and more cross links formed (Instead collagen is laid down resulting in scarring of fibrosis)
what are the functions of secreted proteoglycans
-Resistant to compression(alters charge density on pressure)
-Hydrated gel allows motion of nutrients and waste products about isolated cells
-High charge acts as a binding site for many molecules : growth factors (FGFs) and cytokines, released on proteoglycan damage
-Co-receptors / inducers for growth factors
what do cell adhesion molecules do
-Link the extracellular matrix ( including collagen and proteoglycans )to the cell surface
what are the key features of laminin ( a protein in the basement membrane)
-Heterotrimeric protein ( has three different polypeptide chains - alpha,beta,gamma)
-Has a globular region
-Binds to intergin receptors
what are integrins
Integrins are a family of heterodimeric cell surface receptors that mediate cell-matrix interactions by linking the extracellular matrix (ECM) to the cytoskeleton inside the cell.
what are the key features of intergins
-Dimeric molecules(composed of alpha and beta subunit)
-Theyre heterodimeric matrix receptors
-Specific integrins bind to specific ECM components
what are focal adhesions
Focal adhesions are dynamic, protein-rich complexes that form at the plasma membrane where cells adhere to the ECM via integrins. They play a key role in linking integrins to the actin cytoskeleton and facilitating cell signaling.
Role of focal adhesions
Focal adhesions(have 2 fibroblasts)-actin-adherens junctions
Focal adhesions form where integrins bind to specific sequences on ECM molecules
Roles: anchor cells to the ECM,cell migration and signal from the ECM
what do hemideosomes do
(Bind epithelial cells to basement membrane )
Specific integrins bind laminin in the basement membrane to intermediate filaments via plectin
what is FAK
Focal adhesion kinase
what does the effectiveness of a hormone system depend on
Effectiveness depends on :
-Conc of free hormone
-Number of receptors on cell
-Affinity of hormone for receptor
-Efficiency of amplification
-Stopping signalling
what are the three main hormone families
-Amine derived hormones
-Peptide hormones
-Lipid and phospholipid hormones
What does the term KD (dissocation constant) mean
-used to describe the affinity between a ligand (such as a hormone) and its receptor
-It is defined as the concentration of the ligand (hormone) at which half of the receptors are occupied or bound by the ligand.
Examples of second messenger systems
-Adenylate cyclase
-Guanylate cyclase
-Calcium and calmodulin
-Phospholipase C catalyzing phosphoinositide
what three things determines the concentration of hormone seen by target cells
Rate of release-synthesis and secretion of hormones are the most highly regulated aspect of endocrine control , controlled by positive and negative feedback loops
Rate of delivery-high blood flow delivers more hormone than low
Rate of degradation and elimination-shutting off secretion of a hormone with a short half-life causes circulating hormone conc to drop
Two ways to measure levels of hormones (what two tests)
-Radio-immune Assay(here the hormone is the antigen)
-ELISA(here the hormone is the target protein)
where are the receptors for hydrophilic hormones
Hydrophilic hormones - cell surface transmembrane receptors (ion channel linked receptors , enzyme receptors , tyrosine kinases which all must have secondary messengers)
where are the receptors for hydrophobic hormones
Hydrophobic hormones - cytoplasmic receptors, dont need secondary messengers
what is the main function for primary endocrine organs
These organs primarily function to secrete hormones. Their main role is hormonal secretion into the bloodstream, where they act as chemical messengers to regulate various body processes.
what happens if too high calcuim present
Hyperparathyroidism
what happens if too low calcuim
Hypoparathyroidism(too little parathyroidism)
what are tropic hormones
Tropic hormones are hormones that primarily regulate the secretion of other hormones from other endocrine glands. They are not directly involved in regulating physiological processes but instead act on target endocrine glands to stimulate them to produce and release their own specific hormones.
what produces primary trophic factors
-hypothalamus
does the anterior pituitary produce primary or secondary tropic hormones
-secondary
what gland is the main target for tropic hormones
endocrine gland
what are the three hypothalamic nuclei(that i need to know )
(paraventricular , supraoptic and arcuate nucleus are the three we need to know )
what does the hypothalamus do
The hypothalamus is a crucial part of the brain that serves as a link between the nervous system and the endocrine system. It plays a central role in regulating various physiological processes, including hormonal regulation, temperature control
what are tropic hormones
These are hormones secreted by hypothalamic neurons, which are released into the bloodstream to regulate the activity of the anterior pituitary gland
Are there any tight junctions in the anterior pituitary
no
Hypothalamic neurones produce hypothalamic releasing and inhibitory hormones , carried in the portal vessels to what gland
anterior pituitary glands
What are the seven tropic hormones of the hypothalamus (5 pathways)
TRH-Thyrotropin releasing hormone
CRH-Corticotropin releasing hormone
GnRH-Gonadotropin releasing hormone
GHRH-Growth hormone-releasing hormone
GHIH-Growth hormone-inhibiting hormone
PRH-Prolactin-releasing hormone
PIH-Prolactin-inhibiting hormone
what are the 5 cell types in the anterioir pituitary cell , that the tropic hormones act on
-Thyrotropes (respond to TRH)
-Corticotropes(respond to CRH)
-Gonadotropes(GnRH)
-Somatotropes(respond to GHRH)
-Lactotropes(respond to PRH/PIH)
what is the mechanism of control (a response to a stimlus from the hypothalamus)
-stimulus detected
-hypothalamus releases tropic hormone 1 to the anterior pituitary
-This releases tropic hormone 2 to the endocrine gland
-This produces hormone 3 to the target tissue and a response is made
where is ADH produced and released from (a levels)
-Produced in the paraventricular hypothalamic nuclei
-Released by posterior pituitary
What is the secretion of ADH induced by
-Secretion of ADH induced by
Central osmoreceptors responding to increased osmolarity
Reduced plasma volume triggers baroreceptors in aortic arch which signal via vagal nerves to CNS
Angiotensin 2
what does ADH do
Binds to G coupled receptors in blood vessels and kidney collecting duct
Blood vessel smooth muscle constriction
Kidney for water resorption
Increases water retention and blood pressure
what does blood vessel smooth muscle do (hint-pressure of blood and diamter of blood vessel)
-Causes vasoconstriction and lowers vessel volume
-Blood pressure rises
what is the process for increasing water resorption on collecting duct
-Aquaporin 2 inserted
-Stimulates NaCl uptake (produces osmotic gradient for water uptake)
-Increases metabolic activity of these cells (ATP needed for Na ion resoprtion)
-Moves 3 sodiums for 2 potassium
where is oxytocin produced from and released by
produced in the hypothalamus, specifically in the paraventricular nucleus and supraoptic nucleus
-Then released by the posterior pituitary
what gland released ADH and Oxytocin
Posterior pituitary gland
what gland releases TRH,CRH and GnGH/GHIH
anterioir pituitary
How does ACTH and cholesterol uptake in the Adrenal Cortex occur
-ACTH released by the anterioir pituitary
-ACTH signals increases uptake of and debranching of cholesterol into pregnenolone in the adrenal cortex
-When ACTH present cortisol and corticosterone produced
-Corticosterone converted to aldosterone when angiotensin 2 present
what is the process that occurs when CRH,ACTH and cortisol is secreted(CRH first)
-CRH produced and secreted in the hypothalamus
-In response to the CRH ,the anterior pituitary releases adrenocorticotropic hormone (ACTH) into the bloodstream.
-The ACTH binds to receptors on cells in the adrenal cortex and causes the activation of cholesterol uptake which is then converted into pregenolone , which is then converted into cortisol
What are the three functional domains for steroid hormone receptors(three parts of a steroid hormome receptor)
-Ligand binding (steroid binding) domain
-DNA-binding domains
-Ligand depdent transcritpion activating domain
what is the process of steroid hormone binding
-Steroid binds to specific intracellular receptor
-Receptor undergoes a conformational change
-This causes inhibitory protein complex to dissociate and exposes the nuclear translocation signal region
-the receptor then binds to the coactivator proteins that induce gene transcription
is cortisol a glucocorticoid
yes
what do glucocorticoids/cortisol do in terms of protein and lipids
-Increases protein break down (catabolism-releasing AA )
-Increases lipid breakdown(catabolism - releasing fatty acids for fuel)
-Induces liver gluconeogensis lowers glucose use by most cells , raises blood glucose and increases glycogen formation in liver which means glucose saved for CNS etc
where are Mineralocorticoids-Aldosterone produced from and what is it important for (hint-electrolytes)
Produced by Zona glomerulosa
ACTH needed for secretion but Angiotensin 2 regulates levels
Important for :
NaCl resorption
K+ ions loss
Water resorption
what system regulates aldosterone (a mineralocorticoid hormone)
Aldosterone, a key mineralocorticoid hormone, is regulated primarily by the Renin-Angiotensin-Aldosterone System (RAAS), which responds to changes in blood pressure
what type of cells detect low blood pressure
-Juxta glomerula cells(JG)
what is the process that causes the secretion of aldoesterone
Low Na+/High k+ detected in Distal Convoluted Tubule due to low filtration pressure stimulates Macula Densa (MD) which activates JG cells
JG cells release Renin which cleaves ANgiotensinogen (liver) to Angiotensin 1
ACE (Angiotensin-converting enzyme) on lungs+kidney endothelia converts Angiotensin 1 to Angiotensin 2
Angiotensin 2 causes adrenal zona glomerulosa to secrete aldosterone
what is ANF and why is it released
The atrial natriuretic factor (ANF) is a hormone released by the atrial muscle of the heart in response to increased blood volume or high blood pressure
what are the fucntions for aldosterone(what does it do the levels of K,Na and blood pressure)
-Loses K ions
-Increases soduim and water resorption(so increases blood pressure)
what is the process that occurs in response to stress
-Stress is the stimuli
-CRH is released from the hypothalamus
-ACTH is released from the Anterior pituitary
-causes adrenal steroid production
what is the regulator for aldosterone
-Angiotensin
why does addison disease occur
-occurs when the adrenal glands dont produce enough of a hormone, such as cortisol (reduced glucocorticoids)and aldoesteron (reduced mineralcoroticoid)
what does reduced minerlocorticoid and reduced glucocorticoids result in , in terms of addisons disease
Reduced mineralocorticoid:
-Low blood pressure
-Low blood NA and increased K in extracellular fluids
-Fluid loss
-Muscle weakness
Reduced glucocorticoids:
-Low blood sugar
-Muscle weakness
-Tiredness
where is glycogen stored
-In the liver and muscles
The liver is the neoglucogenesis centre, what does this mean
meaning that it uses other nutrient sources to convert them into glucose (new glucose being made
what is the process for glycogen metabolism (breakdown of glycogen)
-Glycogen is the store of glucose
-1-glycogen is the store , glycogen phosphorylase liberates glycogen which produces glucose
Glycogen synthase in the liver and muscle
2-Glucokinase adds phosphate
3-phosphofructokinase adds second phosphate
what is the bodies response to low glucose
-lowered glucose , so liver converts fatty acids to ketone bodies , these can enter the blood as a way of transferring c2 to other organs from the liver
In the liver we can oxidise fats into 2 acetyl coA molecules and then ships these out as ketone bodies ( so this can then go to other organs)
what are ketone bodies
Ketone bodies are a group of water-soluble molecules that are produced by the liver during periods of low carbohydrate availability(low glucose)
what is the short term and long term problem with having too high of a blood glucose level
he short term problem means glucose is lost in renal filtrate (the urine) , this carriers water and electrolytes with it - leading to dehydration
Long term problem:Induces metabolic changes in many cells , increased / abnormal ECM (fibrosis and glycation) and increased deposition of cholesterol , which can lead to vascular disease which can lead to heart attack etc
is insulin produced when blood glucose level too high
yes
what causes insulin production
-Glucose monitored by beta cells which release insulin when they have lots of ATP, express Glut 2 transporters, intracellular glucose conc directly in proportion to blood glucose
High glucose increases ATP formation which closes ATP gated K+ channels, so once ATP goes up these channels close
-Cellular depolarisation occurs , as sodium is still entering the cell , so membrane becomes depolarized and less negative , this causes the voltage gated calcium channels to open which causes exocytosis and the release of insulin containing vacuoles and goes to nucleus to cause insulin production
what increases insulin secretion
-increased blood glucose
-increased blood free fatty acids
-increased blood amino acids
-Gastrointestinal hormones(food ingested)
what decreases insulin secretion
-Decreased blood glucose (Fasting)
-Alpha adrenergic activity (acute stress)
what is the structure of an insulin receptor
-Two alpha and two beta subunits disulphide linked into a heterotetramer
In simplest form: extracellular alpha subunits-insulin binding domains
Transmembrane beta subunits - tyrosine kinase domains
how does insulin signalling work
-Insulin receptor is a Class 2 TKR ( Tyrosine kinase receptor)formed from 2 alpha units which bind to insulin and 2 transmembrane and intracellular parts which are the beta units which have the auto phosphorylation sites ,(disulphide linked tetramers , which remind together continually )
-Two alpha and two beta subunits disulphide linked into a heterotetramer
In simplest form: extracellular alpha subunits-insulin binding domains
Transmembrane beta subunits - tyrosine kinase domains
-Insulin binding to alpha subunit causes auto-phosphorylation of beta subunits, allows other molecules to bind and get phosphorylated
-Induces docking of downstream signalling proteins especially insulin receptor substrate 1
what are the effects of insulin signalling
1-Rapid fusion of intracellular vacuoles with the cell surface , these carry insulin dependent glucose and AA transporters in their membrane causing the plasma membrane to become more permeable to glucose and AA , when insulin levels drop the transporters are lost from cell surface
-This occurs in every cell but red blood cells , neurons and beta cells of pancreas
2-Activation of intracellular enzymes needed for glycogen production and glucose use
3-Increase in gene expression for cell growth and division
what is the pathway of insulin binding to its insulin receptor
-Insulin binds to receptor causing phosphorylation and allows substrate (IRS) to bind which then gets phosphorylated which can then interact with PI-3 Kinase
-This further phosphorylates it , increasing its charge , deforms the membrane , and opens up binding surfaces for other enzymes (PDK-1)
-PDK-1 is brought in and binds , becomes phosphorylated and this allows phosphokinase B to bind and get phosphorylated itself
-This PKB phosphorylates proteins on the vesicles , causes these to fuse with cell membrane
-PKB phosphorylates glycogensynthasekinase 3 , turning it off (turns off an enzyme which would naturally inhibit glycogen synthase - inactivates an inactivator)
how is PKB activated in the insulin receptor signalling pathway
Insulin Signaling: PKB is activated by insulin through the insulin receptor signaling pathway, which leads to the activation of phosphatidylinositol 3-kinase (PI3K) and subsequent activation of PKB.
what does PKB (protein kinase B ) do in terms of glucose
-Increases activity of glyocgen synthase
-Glucokinase
Decreases activity of glycogen phosphorylase (lowers glocuse use)
what does insulin do
-promotes protein formation and storage
-Promotes uptake of amino acids into cekks
-Increases gene transcription and translation
-inhibits AA use in gluconeogensis
what type of cells produce glucagon
alpha cells
why is glucagon released
when blood glucose level too low
how is glucagon formed (what is the response to low blood glcuose)-the ionic control of glucagon secretion
-Low blood glucose leads to low ATP, closes ATP depdended K channels
-Leads to depolarisation and opening of voltage gated soduim channels
-Results in further depolarisation+ voltage gated calduim channels opening
-Cuases glucagon release and induces glucagon formation
(depolarisation = potassuim going out and soduim coming in)
overall , what does glucagon cause
Glycogenolysis in liver increasing blood glucose
Causes gluconeogenesis , liver forms glucose from AA
Increases AA uptake by liver
-Insulin - AA used for growth
-Glucagon - AA used for energy (AA taken up and used in gluconeogenesis)
what type of cells produce testosterone
Leydgi cells
what type of cells are spermatogonium
stem cells
what do round cells differentiate into in spermiogensis
spermatozoa
what are leydig cells
Leydig cells are specialized cells found in the testes that are primarily responsible for producing and secreting testosterone, the main male sex hormone
what does LH stand for
luteinizing hormone
In response to what hormone doe leydig cells produce testosterone
luteinizing hormone (LH)
what does FSH stand for
follicle stimulating hormone
what is an AR
Androgen receptor
in sertoli cells in the testes , what does the FSH hormone stimulate
-FSH (follicle stimulating hormone) stimulates sertoli cells in the testes to express androgen receptors (AR)
what type of receptor does testosterone bind to
Androgen receptor
what does andogenic effects mean
sexual effects
what does testosterone do (anabolic effects - like growth and tissue / think muscles)
-Increases muscle mass
-promotes bone growth
what are the reproductive effects of testosterone
Drives of mitosis of spermatogonial stem cells and their into entry meiosis
Activates genes in Sertoli cells , which promote differentiation of spermatognia
Lowers GnRH release
Lowers FSH and LH production from anterior pituitary
what is the hormonal action in females ( bullet points including hormones such as FSH)
-Hypothalamus releases GnRh
-GnRh stimulates the pituitary gland to release FSH(follicle stimulating hormone) and LH (luteinizing hormone)
-FSH and LH is released by the anterior pituitary in response to the GnRH
-Estrogen is produced by the granulosa cells
-2 cells , androgen production
what is Dihydrotestosterone (DHT) and how is it formed
Dihydrotestosterone (DHT): A more potent form of testosterone, converted from testosterone by the enzyme 5-alpha reductase.
what do sertoli cells convert testosterone into
dihydrotestosterone
where are granulosa cells and thecal cells found
-found in the ovarian follicles
-Granulosa cells surround oocyte
-Thecal cells surround gransulosa cells
are androstenedione and testosterone an andorgen
yes
Describe the steps that ivolve FSH and LH raises blood 17B-estradoil
-FSH and LH released by the anterior pituitary gland in response to GnRH (Gonadotropin releasing hormone) secreted by the hypothalamus
-FSH is more dominant in the early follicular phase and LH increases as ovulation approaches
-LH stimulates the thecal cells to produce androgens (Androstenedione and testosterone)
-FSH stimulates the granulosa cells ( which are responsible for converting androgens into estrogens )
-In response to FSH , granulosa cells express more aromatase enzyme which converts androstenedione and testosterone into 17B-estradoil
do males have leydig cells or thecal cells
males have leydig cells
females have thecal cells
what is the primary fucntion of leydig cells
-Primary function of leydig cells (in males ) is to produce testosterone in response to LH (luteinizing hormone)
what does LH (luteinizing hormone)
stimulates the leydig cells to produce testosterone
what are the different responses to LH in males and female(one response for males one for females)
-In males the LH stimulates leydig cells to produce testosterone (by converting cholestrol into testosterone)
-In females the LH stimulates thecal cells to convert cholesterol into androgens( testosterone and androstenedione)
what does 17 beta estradiol do
-stimulates growth of uterus
-stimulates groth of granulosa cells in follicles
-stimulates granulosa cells to make more FSH receptors
-Lowers GnRH releases and FSH and Lh production
why does ovulation occur
-when the 17 beta estradoil is high it causes GnRH release
-LH levels rise
-Ovulation is triggered by this surge in LH
what does the surge in 17 beta estradoil stimukate granulosa cells to do (ie what receptors )
stimulate granulosa cells to make LH receptors
How is the corpus luteum formed
-The formation of the corpus luteum occurs after ovulation when the postovulatory follicle transforms into the corpus luteum
-The surge in LH (luteinizing hormone) triggered by high levels of estradiol induces ovulation
-The oocyte is released (for possible fertilisation)
-After ovulation , the follicle that houses the oocyte is considered a postovulatory follicle/ruptured follicle
-The postovulatory follicle transformers into the corpus luteum due to LH
-The corpus luteum secretes high levels of progesterone as well as estrogen
what does progesterone do
-Reduces FSH production from pituitary
-Reduces LH production from pituitary
-Changes uterus for implantation
the uterus has three layers , name the two layers u need to know
-Uterus:Myometrium and endometrium are two of the layers
-Myometirum is a muscle layer
-Endometrium:inner stromal and lining epithelial cells
do both syncytiotrophoblast and cytotrophoblast form the placenta
yes
does Syncytiotrophoblast or cytotrophoblast make HCG(human chorionic Gonadotropin)
Human Chorionic Gonadotropin is made by syncytiotrophoblast
what does HCG do
Human Chorionic Gonadotropin-Signals to the mother to keep the Corpus Luteum and uses the LH receptor on the Corpus Luteum cells
what is luteolysis
-It is the cell death of Corpus Luteum cells , caused by feedback effect of progesterone and lack of pregnancy so no hCG and turning off LH secretion by pituitary so Corpus Luteum is not maintained
provide a summary of the hormonal interactions during pregnancy
-FSH and LH released by the anterior pituitary gland in response to GnRh secreted by the hypothalamus
-A surge in LH stimulates the release of the oocyte(egg) from the ovary
-After ovulation the ruptured follicle transforms into the corpus luteum which begins to secret progesterone and estrogen
-If fertilized, the syncytiotrophoblast of the embryo starts to secret human chorionic gonadotropin (hCG)
-hCG signals to the corpus luteum to keep producing progesterone
-hCG prevents the degeneration of the corpus leuteum, allowing it to continue to produce progesterone
-The corpus luteum continues to produce 17 beta estradiol
-After conception , the hypothalamus and pituitary gland reduce the production of LH and FSH because of the negative feedback provided by rising levels of progesterone and estradiol
during pregnancy what does progesterone do
Blocks further follicle development and ovulation(blocks FSH and LH) so single embryo through pregnancy
Barrier at cervix for sperm entry-mucus plug stops entry of microorganisms (Cervical plug)
Induces uterine endometrium to make a nutrient source for the embryo
Induces breast tissue growth ready for lactation
Keeps the myometrium in a non contractile state
At about 7 weeks there is a luteoplacental shift , the corpus luteum before 7 weeks is producing the progesterone but after 7 weeks the progesterone now starts to be produced by the placenta
in other species (not humans ) before brith there is a rise and decrease in progesterone/estorgen , which one is which
-Reduced progesterone
-Rise in estrogen
Steps involved in the conversion of progesterone into 17beta estradiol stimulated by fetal cortisol(page 124)
-During pregnancy the fetus produces cortisol
-Fetal cortisol stimulates the placenta to convert progesterone into 17a-hydroyprogesterone
-17α-hydroxyprogesterone is an intermediate compound that plays a critical role in the synthesis of estrogens.
The conversion of progesterone to 17α-hydroxyprogesterone occurs in the placenta, primarily via the enzyme 17α-hydroxylase
-The fetal cortisol causes in the placenta expression of 17-alpha-hydroxylase
17α-hydroxyprogesterone is then converted to androstenedione, an androgen
-The enzyme aromatase, present in the placenta, converts androstenedione (or testosterone) into estrone, which is then converted to 17β-estradiol
-So progesterone levels go down , estradiol levels go up
why do CRH levels rise during pregnancy (positive feedback loop)
-Hypothalamus releases CRH
-CRH binds to anterior pituitary
-Anterioir pituitary secretes ACTH to the adrenal cortex
-The adrenal cortex then converts cholesterol into cortisol
-Its a positive feedback loop as cortisol binds to GR(Glucocorticoid receptor ) which causes an increase in CRH production
how is oxytocin release regulated parturition(birth)
The release of oxytocin at parturition (labor and delivery) is regulated through a positive feedback mechanism
