Lecture #9 Flashcards
November 3, 2020
absorption
-major routes are gut, skin, and lungs/gills (exposed to environment) -must cross a membrane to be absorbed
phospholipids
-major constituent of membranes -contain cholesterol -polar, hydrophilic head and nonpolar hydrophobic tails (fatty acid chain) -4 major kinds, one has net negative charge -only small, neutral hydrophobic molecules can penetrate
plasma membrane is a mosaic of ______
-proteins and lipids -much of absorption is governed by proteins (membranes are selective barriers)
six major functions of membrane proteins
- transport 2. enzymatic activity 3. signal transduction 4. cell-cell recognition 5. intercellular joining 6. attachment to the cytoskeleton and extracellular matrix
intercellular joining
-cells at barrier tissues are organized into epithelia (sheets) -different types of epithelia, all are polarized (one side faces environment and one side faces blood) and rest on a basal lamina, this leads to specialization of membranes
typical junctions between cells in epithelia
usually have tight junction which greatly limit the movement of molecules between cells, seals cells together
adherens junction
connects actin bundles between cells
desomosome
joins intermediate filaments
gap junction
allows passage of small molecules between cells
simple epithelia
stratified epithelia
columnar epithelia
cuboidal epithelia
squamous epithelia
apical
faces the environment
basolateral
faces the blood
~ 25% of the genome codes for…
membrane proteins (more than half of all drugs target membrane proteins)
multidrug (ABC) transporters
-the cell’s bouncers -one transporter can expel many different kinds of chemicals -always being adapted to the environment, adding more of the kinds that are needed and taking away ones that are used less
distribution
-once absorbed, a compound (toxicant/drug/nutrient) has to move from the site of absorption to the site of action -a property of both organisms and cells
continuous capillary
fenestrated capillary
discontinuous capillary
leaks compounds from the blood into the liver so they can be detoxified
intracellular sequestration
can store chemicals after they’ve entered the cell to prevent them from causing harm plant cells –> vacuole animal cells –> lysosome
if Hg reacts with cysteine, mercury will accumulate in…
muscle/proteins
metabolism and excretion
-occurs in LIVER, kidneys, and lungs -happens on a cellular level
Membranes can take things out of the cell or bring them in. This sometimes leads to…?
removing beneficial compounds or taking up harmful ones
What compound is this?
alpha-amanitin, found in poisonous mushrooms
What compound is this?
flunterazipam (roofies)
the mechanisms by which chemicals cause harm
- mutations 2. epigenetic mechanisms 3. interference with cellular signaling 4. interference with metabolism 5. membrane disruption
To investigate the mechanisms by which chemicals cause harm, we …
run bioassay systems on other species
ames assay
used to determine mutagenicity
To determine if a compound causes harm, we can look at the following endpoints:
gene expression, morphological defects, protein modification, etc…
two general mechanisms of intoxication
- calcium signaling 2. oxidative phosphorylation
calcium signaling
-low intracellular calcium concentrations, high extracellular concentrations -calcium is a signaling molecule -level increases in response to stimuli -toxicants cause the cell to release stored calcium, convinces the cell that things are very bad –> programmed cell death -calcium also signals development of sea urchin eggs after encountering sperm, an early signal would prevent the sea urchin from properly developing bc no male DNA
oxidative phosphorylation
-uses energy in nutrients to produce ATP -occurs in mitochondria -toxicants/pesticides interfere with production of ATP
