Trigger 10 Flashcards
what is tryosine
precursor of all catcecholamines
synthesised from phenylaline
describe the sysnthesis of catecholamine neurotrasmitted pathway
tryosine dihydroxyphenylaline dopmaine noradrenlaine adrenlaine
where is dopamine most abundant
corpus straitum
describe the nigrostriatal pathway
key dopamine pathway
cell body in the substaial nigra, moves up to corpus straitum
70% of dopmainic neurones are found here
desrcibe the misocortical pathway
starts in VTA
through forebrain up to the cortex
what happens in parkinsons
dopamine neurones are dyding
ridig muscles due to too much inhibtion of movement
effect of less parkinsons on the motor coretx
the Dopamin neurones die which causes a redcution in inhibition
results in a overexcition of inhibitory signals to thalamus
reduction in glutamine so reduction in motor cortex leading to bradykinesia
what is bradykniesa
suppression of voluntray movement
why is L-DOPA used to treat parkinsons
Dopmaine is hydrophilic so cant cross BBB
L-DOPA is take pheripherally and can then cros the BBB where is it converted to dopamine
How is dopamine broken down
broken down by homovanillic acid via DOPAC and 3MT
what is the use of COMT
prevents L-DOPA being broken down into another dopamine precusor
what is MAO-B used for
used in the treatment of depression and parkinsons
prevent the breakdown of dopamine
what is alzhemirs
progressive neurodegeneration
most common cause of dementia
symptoms of alzhemirs
- loss of memory, cognitive ability, communication
- changes in mood and personality
- forgetting recent events, unable to store new infotmaion in the temporal lobe
what is huntingdons disease
progressive neurodegeration reduces lifespan (15-20yrs)
symptoms of huntingdons
cognitive disorders - impulse control, task organisation. flexibilty, learning
movement disorder - involuntray jerking. twitching movements, rigidity, speech
describe the ubiqutin protesome system
Ub activated by ubiquition-activiating enzyme (E1)
Ub then transferred to ubiqutitin-conjugating enzyme (E2)
protiens that are targeted for degreation have a region on them called degrons
E3 ubiquitin liages binds to degrons
Poly Ub signals for protesomal degredation
protein substrate in degraded, generting short peptides and free ubiquitin that can be resued
describe apoptosis
programmed cell death membrane blebbing and cell seperates into membrane bound apoptoic bodies cell shrinks chromatin condenses nuclear DNA fragments attracts macropahges to phagocytose cell
describe necrosis
usually uncontrolled and in respne to acute trauma
membrane blebbing
cell contents including lysosomes enzymes spill over inducing inflammaroty response and tissue degradeation
cells and organelles swell and burst
describe the extrinsic apopotic pathway
Fas ligand binds to death receptor
protien recruitment and form death-inducing signalling complex
activatses caspase 8 (initator)
activates caspase 3 or 7 (exceutioner)
describe the intrinsic pathway
cytotoxic stress
translocation of pro-apoptoic Bel-2 family to mitochondria
mitochondrial cytochrome C realesed
oligomerisation of pro-apoptoic factor Apf-1 - forms apoptosome
recruits caspse 9
activates caspase 3
what is autopahgy
fromation of membrane bound structure
turns into an autophagosome
lysosom merges
autolysosome
what is radio ligand binding
important when developing new drugs
the time a lignad binds to a receptor
drug binding affinity
how likely it is for the drug to be bound to the receptor
longer time = greater affinity
equation radio ligand binding
conc Drug x conc Receptor/ conc DR = kd
kd = dissocation constant
describe competeive biding experiments radioligand binding assay
fixed conc radiolabel ligand with know bidning kinetics
incubated with increasing conc of unlabelled (competitive agonist/antagonist) drug B
creates a sigmoid curve log graph
what is the IC50
amount of the new drug that is required to make 50% binding of the old drug
what is the cheng-prusoff equation
IC50/(1+ (conc A/Ka)) = Ki
Ka =Kd of the old drug
what dopmaine receptors are Gas
D1 ans D5
what dopmaine receptors are Gi/Go
D2, D3, D4
DNA methylation
the addition of a methyl group to one of the bases in the DNA chain, and is a key epigenetic modification.
what are histones
Histones pack and order DNA into structures known as nucleosomes so that it fits within a cell’s nucleus.
what is histone modifacation
Histone modifications are post-translational modifications that regulate gene expression
what are non-coding RNA
are RNA molecules transcribed from the genome that do not encode proteins.
what is Epigenetics
Epigenetics is the study of heritable changes in gene expression (active versus inactive genes) that do not involve changes to the underlying DNA sequence — a change in phenotype without a change in genotype — which in turn affects how cells read the genes.
what is siRNA
Single-stranded RNA molecule (usually from 21 to 25 nucleotides in length) produced by the cleavage and processing of double-stranded RNA; binds to complementary sequences in mRNA and brings about the cleavage and degradation of the mRNA.
