Trigger 5 Flashcards
Describe the MAPK cascade (mitogen activated protein Kinase)
Grwoth factor and insulin ligands bind to receptor
Dimersation
tryosine domains trans-auto phosphorylate themselves
attarct any protien with a SH2 receptor
Grb2 attached
SOS activated, SOS is a GEF
activates Ras, GTP in activate site of RAS, stimulates pathway
activates Raf
phosphorylates futher kinase
ERK binds to DNA
What is DCC
deleted in colorectal carcinoma
Role of DCC
acts as a tumour supressor and proto oncogene
activates MAP kinase cascade
has its own ligand - nitrin 1
dependance receptor
with ligand, stimulates MAp kinase cascade
without lignad it actiavtes caspase leading to apoptosis
Role of APC
inviolved in Wnt signalling
when there is no lignad, APC part of destruction complex
if APC mutated it inhibits kinase of destruction complex, unregulatted growth
desrcibe the stages of Wnt siganlling when absent
no ligand binding to frizzled complex of APC, axin and a kinase = destruction complex phophorylates B-catein Bcatein ubiquinated protesomnal degradation no transcription
desrcibe the stages of Wnt siganlling when present
Wnt binds to Frizzled dishevelled activated inhibits kinase of destruction complex B-catein not phosphorylted so not ubiquinated transolation to nucelus gene transcription
What is Inflammatory bowel dsease
relapsing and remitting conditon chaarctized by chronic inflammatory at sites in the GI tract
results from cell mediated immune response in the GI mucosa
tests for IBD
primarily done without lab tests lab tests -stool culture - ova and parasite examination of stool - coalic test - WBC test
treatments for IBD
anti-inflammatory drugs
steroids
immunosuppressants
antibiotics
Crohns disease
can affect any part of the GI tract
80% in the SI
Affected areas are patchy
can casue narrowing of the GI tract, ulcers or fistulas
symptoms of Crohns
diarrohea abdominal pain fatigue weight loss blood or mucous in faeces
Ulcerative colitis
primarily affects the surface lining the colon
tissue inflammation normally continous
symptons of Ulcerative colitis
diarrohea
cramping pain
fatigue
loss of appetite
What are colon polyps
small clumps of cells that form on the lining on the colon
neoplastic
Non-neoplastic polpys
sypmtons of colon cancer
change in bowel habits rectal bleeding persistent abdominal discomfort weight loss weakness/fatigue
diagnosing colon cancer
colonscopy
blood test
What are DNA repair genes
code for proteins whose normal function is to correct errors that arise when cells duplicate the DNA prior to cell division
Lynch syndrome/HNPCC
inherited disorder that increase rick of many types of cancer
faulty repair genes
MLH1, MSH2, MSH6 and PMS2
desribe the metastic cascade
release of tumour cell from primary tumour and invasion of basement membrane, secrete MMPs to breakdoen tissue
intravasion into a capillary
in the blood supply, invades the immune system
- leukocyte bind to it
- platelts bind, can be protective
- met with other tumour cells
arrest and extraversion into target organ, produces CAM1 to help stick to endothelium
growth in new environment and formation of secondary tumour
What is bioavailabilty
the proportion of an administered drug that reached the systemic circulation
area under the curve or oral does/area under the curve of IV dose
% of measured relative to IV dose
Factors that influence bioavailabilty
nature of the drug
- Gi transit and digestion - first pass metabolism - breakdown of the drug by the liver before it has entered the systemic circulation - route of administraion - IV direct into blood stream, oral breakdown via GI tract - Lipophilicty - ability to cross plasma membrane
Volume of distribution
apparent voulme of distrubution, theoritcal value
after absorption, drug equilibrate bewteen plasma and tissues
drug conc measure in plasma, less in plasma = more distrubuted
factors affecting Volume of dustribution
drug size drug lipophilicty plasma protein binding body compostion patient age/gender
measuring volume of distribution
measuerd following IV administraion of known amount of drug
amount of drug in body/plasma conc
e.g high plasma=low Vd = drug not widely distributed
Drug clearance
volume of plasma cleared of the active compound per unit of time
Zero order kinetics
constant amount of drug cleared per unit of time
irrelevant of how much you intake
first order kinetics
constant proportion of drug cleared per unit of time
double amount of drug - double time taken to clear
plasmas half life
time taken for plasma conc of a drug to reduce by half
drug clearence and volume of distibtuion affect plasma half life
Drug targeting
targeting of drug delivery to site of action
benefits of drug targeting
reduces side effects, espcailly when non-specific mechanisms of action
allows lower dose to be given
more predictable biological effects
recombinant proteins
produced by gentically modified organisms
follows same process as recombinant dna
advantages of recombinant proteins
high % of purity
recombinant protiens show higher specific activity
continous supply
high leves of consistency is seen in batch to batch productions
oral administraion
via mouth and swallowed
absorbed in small intestine
sublingual adminstration
absorbed directly from oral cavity
pass directly into systemic circiualtion
rectal administration
required for drugs to either produce a local effect or to produce systemic effects
often unrelaible
useful in patients who are vomiting
stage of glycolysis
glucose glucose 6P fructose 6P fructose 1-6P G3P pyruvate
glycolysis
breakdown of glucose
gluconeogenis
non CHO stores forming glucose
stages of gluconeogenis
TCA cycle - Oxalocate pyruvate and phophophoenolpyruvate G3P fructose 1-6P fructose 6P glucose 6P glucose
Glycogenolysis
fromation of glucose from glycogen
glycogenolysis stage
glycogen
(phosphorylase b --> phophoryalase a)
glucose 1P
(phosphoglucomutase)
glusoce 6P
(glucose 6 phosphatase)
glucoseglycogensis
formation of glycogen
stages of glyogensis
glucose
(hexokinase)
glucose 1P
(phosphoglucomutase)
glucose 6P
UDP glucose
a glucose
(glycogen synthase)
glycogen `Glucagon
relaesed from islets of langerhans
stimulated by decreased blood glucose
effects of glucagon
on blood glucose
- stimulates glycogeolysis, inhibits glycogen
- stimulates gluconeogensis, decreases PFK activity
- increase blood glucose conc
on blood fatty acid and ketoacid
- increases lypolysisand inhibits fatty acid synthesis
glucose transporters
transmembrane proteins
faciliates the movement of glucose across plasma membranes
driven by concentration gradient
binding of glucose causes a transforamtional change
GLUT 1
found in most cells function - glucose uptake
GLUT 2
found in - liver, kidneys, small intestine, pancreas function - rapid uptake or relase of glucose
GLUT3
found in - brain, kidneys, placenta function - glucose uptake
GLUT 4
found in - liver, muscle and fat function - insulin stimulated glucose uptake
GLUT 5
found in - small intestine function - glucose uptake
inuslin
peptide hormone
prodcued by beta cells in the iselts of langerhans
regulates metaboism of CHO, Lipid and protein
Insulin recepetor
transmembrane, tyrosin kinase receptor two alpha and two beta subunits insulin binds to alpha subunit beta subunits phosophrylate themsleves activates intracellular proteins generates response
electromagentic sepectrum order
radio wave microwaves infrared visible light ultraviolet xrays gamma rays
