Steroid hormone pathway for cell communication (e.g testosterone)
Testosterone + carrier protein (prevents it disintegration as hydrophobic and lipophilic)
- reaches target - detatches from carrier protein- crosses PM an NM- SH (testo)+ Receptor on promoter (TESTOSTERONE TESTOSTERONE RECEPTOR COMPLEX) - recruits TF and TA for translation and transcription
AIS treatment and cause
- defective testosterone receptor
-X linked recessive disorder - Female cannot
-Treatment:
Complete- vagionoplasty, estrogen
Mild: Androgen, hypospadius repair
Flutamide what does it do
potent inhibitor of testosterone
- non streoidal anti androgen
- no 4 ring structure
What are anti estrogens used for
- breast cancer
- BC often caused by excessive estrogen
intracellular transduction pathway (inside the cell)
- extracellular signal + receptor - intracellular signalling proteins - splits to metabolic enzyme (altered metabolism) or gene regulatory (altered gene expression)
Extracellular responses diagram (on the surface of cells)
Extracelluar signal+ cell surface receptor- slow (Transcription)- altered protein synthesis OR fast (intracellular signalling) lead to altered protein function
- BOTH lead to altered cell behaviour
cAMP endocrine pathway
signal molecule+ G protein coupled receptor– a of HT G protein complex activated– activates adenylyl cyclase– Convertes ATP to cAMP- activates PKA
Phosphorylation of of protein kinase
- transfer of phosphate of ATP to SER, THR, TYR (of target protein)
- this activates target protein or inactivate sometimes = REVERSIBLE
What response phosphorylation give
PKA– [phosphorylates TARGET PROTEINS] –which are metabolic. enzyme (altered metabolism) or gene regulatory protein (Altered gene expression)
How does glycogen turn to glucose with the trigger of PKA
adrenaline(SM) — PKA– phosphorylase kinase active– acts as signal for Glugogen phosphorylase to activate– glycogen cleaved onto muscle cell receptors and onto glucose making it active for muscle action
How is adrenaline also involved in the fight or flight response
- adrenaline (produced my adrenal medulla) + GPCR on muscle cell (b adrendenic receptor) - glucose then made as a store of energy
What do beta blockers do
(altering pathway to stop metabolic action) FAST RESPONSE
- blocks interaction of adrenaline with receptor- treats hypertension (high BP), stops heart muscle contraction by stopping glucogenlysis
How can we alter the triggering pathway to alter gene expression (SLOW RESPONSE)
- CREB activated by PKA (transcription factor)– binds to CRE of promotor of somatostain gene– recruits CBP (creb binding protein) [transcriptional co activator] – transcription and translation– new protein
How are signals from outside the cell converted to inside
- Extracellular signal delivered through blood stream/ adjacent cell
- receptor picks this up and converts it to intracellular signals
- determines the cell needs to be replicated
How do the amount and type of signal determine cell behaviour
- cell respond to multiple of signals
- many signals together of different combinations result in different survival behaviour
- all have independent factors and protein receptors in how they will convert extracellular signals to intracellular events that will ultimately control cell behaviour
- absesnce of signals mean cell enters apoptosis
How do transmembrane receptors relay signals to intracellular signals and alter cell behaviour
EC signal membrane bound receptors—- intracellular signals—- metabolic enzyme (altered metabolism), (cytoskeletal protein) altered cell shape, (transcription regulator) altered gene response
How can we turn enzyme activity on or off
ADDING PHOSPHATE (kinase) REMOVING PHOSPHATE (phosphatase) - adding phosphate by ATP= confirmational change in enzyme = active
How does an epidermal growth factor lead to cell proliferation
- epidermal growth factor+ receptor tyrosine kinase (two halves)– two halves come together (dimer)– phosphate by ATP adds to protein such as RAS – GTP will also add to RAS to activate it too
What are the stages of the cell cycle G0,G1, S, G2 (interphase
G0- cyclin-dependent kinases disappear- cell remain in the G0 phase until there is a reason for them to divide
G1- cell grows- most proteins made for DNA replication and mitosis (monitor intra+extra environ to check if conditions correct)
S-DNA replicates chromosomes perfectly (ensures double genetic material)
g2- more checks that genome fully replicated and more growth
What are the main regulators of the cell cycle and how are they activated
- Cyclin- cyclin dependent kinase
- activated with cyclin attached to it (heterodimer)
- to deactivate cyclin breaks down
- main regulators
How does S phase get triggered to start replication
- G1 forms a pre replicative complex preparing s phase containing Cdc6 (which inhibits it proceeding to s phase)
- Scdk phosphorylate cdc6– degration of Pcdc6— enables replication to proceed– assembly of replication fork– DNA replication
What factors does p53 check for in damaged DNA in G1
- sees if there is UV ionizing radiation. lack of nucleotides, oncogene signalling (genes that can cause cancer), lack of oxygen)hypoxia)
- p53 fixes it - cell cycle arrest (stopping) or cell death
How does Rb check for extracellular unfavourable environments in the cell cycle
- active Rb and inactivates transcription factor = NO TF binding- NO CELL GROWTH
- when Growth factor released– upregulate cyclin– cyclin cdk phosphorylate Rb- cant bind to TF= cell proliferation
When can you see chromosomes and when can you not
- cannot see chromosomes in interphase as DNA is decondensed (being sileced by heterochromatin)
- in mitosis – chromosome condense- chromosomes seen
