Ch.3 Flashcards
What are some examples of possible uptake and elimination routes for a toxin in an fish
- Biotransformation
- absorbing water
- food
- dermal uptake
- loss from gills
- loss from urine and feces
What is the black box approach
a simplified way of modeling the uptake and elimination of a substance within an organism,
-uptake and elimination are arrows outside the box with possible redistribution, biotransformation and detoxification inside the box
What is the main assumption for the black box approach
that there is only 1 method of uptake and elimination that is dominant
What are the main assumptions inherent in any mathematical model of uptake and elimination
- uptake and elimination happen in one compartment
- compartment is instantly and homogeneously mixed
- kinetics and rate coefs are constant over time
- no biotransformat or organism effects take place in this compartment
What is a compartment in mathematical modeling
a way to simplify an organism, sometimes the entire organism is represented by a compartment
True or False: a compartment is usually represented by an organ or other bordered area in the body
False, usually animals are represented by a three compartment system (fat storage, blood, and liver)
What are the typical 3 compartments in an uptake and elimination model
- fate storage
- blood (intestine in, urine out)
- liver (biotransformation going out)
What kind of curve is represented most commonly
a sigmoid curve
what are the x and y axises of a sigmoid curve
y = concentration x = duration of exposure
what are the stages of a sigmoid curve
- uptake mechanisms are more dominant
- elimination processes come into play
- uptake and elimination are in balence
What is the difference between steady state and equilibrium
steady state includes energy requiring processes while equilibrium does not
what is body burden
the steady state concentration expressed as mg contaminant per g of tissue or mg per individual
Why is prediction of contaminant accumulation necessary
- effects are due to conc in target area not abs conc
- top predator exposures are often food related
Define bioconcentration
accumulation in/on an organism from water
define bioaccumulation
net amount of a contaminant on/in an organism from all sources
True or False: as models become more complex they become more predictive
False, it means more variables must be estimated that could result in less accuracy
what was to occur for a compound to be toxic
they have to come into contact with their site of action at a sufficient
what are some ways contaminants can enter an organism
- skin (dermis)
- gills
- pulmonary surfaces
- gut
what are some ways contaminants may entre a plant
- roots
- stomata
- other epidermal surfaces
how many stomata can be on a single leaf
6 million
True or false: stomata open and close in response to many environmental signals
true
When do stomata open
in high humidity, light, low carbon dioxide
when do stomata close
dry, dark, high CO2
Where do stomata connect to?
to air spaces in the leaf and the internal cells (parenchyma)
what are parenchyma
thin walled cells with large central vacuoles
What are stomata involved in
- photosynthesis
- respiration
- protein synthesis
- storage
- repairing plant tissues
how does a plant take in airborne pollutants from the environment
uptake via stomata -> pollutant moves to intracellular spaces around parenchyma - > compound dissolves into cell surface water->parenchyma cells can store, sequester or biotransform the compound
What are stomata connected to
the air spaces in the leaf and the internal cells
What is parenchyma
Thin walled cells with large central vacuoles
What are stromata involved in
- Photosynthesis
- Respiration
- Protein synthesis
- storage
- repair of plant tissues
What are the 3 general routes into cells
- Lipid
- Aqueous
- Endocytotic
Explain the lilipid route into the cell
-lipophilic contaminants and small uncharged polar molecules diffuse through the lipid bilayer
Explain the aqueous route into the cell
- Membrane transport proteins are involved
- -> channels - porins may be gated or ungrated, barrel-shaped proteins
- -> Carrier proteins -Can involve active transport mechanisms - Can be symporters, antiporters
Explain Endocytotic as a route into the cell
-Taken up by endocytosis into vesicles and processed
What must happen before a substance can be taken up into a cell
It must interact with the surface
How does a substance interact with the surfaceinteract interact with the surface
Adsorption
Explain Adsorption
The accumulation of a substance at a boundary of two phases (often the solution to solids)
What is the resulting equilibrium from adsorption
an equilibrium between the bulk solution and the solid phase
What force interactions are in adsorption
- H bonding
- Van der Waals
- hydrophobic interactions
How is adsorption described mathematically
Using the Freundlich equation
X/M = KC^(1/n)
Explain the symbols in Freundlich equation
X/M = KC^(1/n)
X=Amount adsorbed
M = Mass of absorbent
K = Derived constant
C = [Solute] in solution after adsorption
n = Derived constant (less then or equal to 1
n is often close to 1 if the concentration of the solute is low
What does it look like when you graph X/M on the y axis and C on the X axis
a classic sigma curve
Can you linearize both sides
Yeah you log(X/M) = log K, + (logC/n)
What is Freundlich isotherm mostly used for
- Adsorption of liquids to solids
- i.e. pollutants to sediments or soils
- i.e. adsorption of compounds or soils to biota with a very large surface area to volume ration, particularly microorganisms
What is the Langmuir equation
X/M = ((abC)/(1+bC))
X,M,C are the same as with the Freundlich isotherm
a = maximum adsorption amount
b = affinity (refliects bond strength
What can the Langmuir equation describe
-Toxicant movement onto biological surfaces including a;gae gills and zoo plankton
What are the models talked about in this unit simplifications of adsorption
- Contaminant movement into the organism may be a multi step process
- Rapid adsorption may be followed by a slower diffusion step
What is adsorption influenced by
- Structural composition of the chemical
- Organic Carbon content of the soil
- pH of the medium
- Size of soil particle
- Temperature
What are the two types of diffusion
- Simple
- Facilitated
Explain simple diffusion
- No energy input required
- Molecules move across membrane down its concentration or electrical gradient
- May include a channel protein: 1. May be gated or ungated. 2. Passage through the channel can be influenced by ion change or size
Explain Facilitated Diffusion
- energy input required
- Molecules move faster than predicted down its concentration or electical gradient
- carrier protein involved
- may become saturated or inhibited
What type of diffusion do large/ highly charged molecules require
-facilitated or carrier transport, or active transport to cross the cellular membrane
What does diffusion of acids and bases depend upon
their pKa and the surrounding pH
- If the ratio of uncharged to change form is greater then 10:1, absorption into the cell will occur
How can diffusion be expressed mathematically
By Fick’s Law (ds/dt) = -DA(dC/dx)
ds/dt = Rate of contaminant movement across a surface
D = diffusion coefficient
A= Surface area diffusion is occuring over
dC/dx = Concentration gradient (or electrochemical)
True or False: Many models of bioaccumulation include calculations of rates of diffusion into or out of various compartments
True
What is involved in active transport
- Energy required (either ATP or PMF)
- Carrier proteins involved
- May become saturated or inhibited (e.g. Na+/K+ pump (ATPase)) or (e.g. Cd2+ may be imported as Ca2+ analog)
True or false: Endocytosis is an important route for contaminants ingested with food
True
True or False: endocytosis is often receptor mediated
True
True or False: endocytosis usually does not require energy
False
Explain iron assimilation as a type of endocytosis
- Fe3+ and perhaps other metals bind to transferrin (siderophore)
- Metal: protein complex binds to receptor on cell surface
- Bound receptor complex moves to clathrin coated pits on the cell surface.
- Vesicle formed
- Receptors are recycled.
- Clathrin removed, endosome acidifies
- Iron dissociated, transferrin and receptor are recycled.
- Entire cycle 16 min (4 min to move receptors to coated pits, 5 min to form endosome, 7 min to sort and recycle receptors back to the surface).
- Liver may uptake 20,000 iron atoms per minute by this process
Explain first order kinetics
- most commonlu observed and applied for bioaccumulation models
- Reaction rate is most rapid with excess substrate (rate decreases with less sub)
- reaction is basically irriversibe (A–> B)
- Called first order because reaction velocity depends on the first order of magnitude of conc A
- rate constant can be determined from slope of initial reaction vs [A]
- if reverse reaction is occuring you also have to look at that
Explain seccond order kinetics
- Apply to reactions in which molecules of a reactant must come together
- 2A->B
- V=-k[A]^2
- units of k are (mol/L)s^-1
Explain zero order kinetics
- USed to describe a saturated system in which the reaction rate is independant of the concentration of reactant
Define Biotransformation
biologically mediated conversion of one chemical compound to another
Does biotransformation often involve enzymes
Yes, saturation and inhibition are possible
Explain Inhibition
Decrease in reaction rate due to interactions between enzymes and other compounds
What are the two types of inhibition
- Competitive
2. Noncompetitive
Explain competitive inhibition
inhibitory substance binds into active site, blocks substrate
Explain noncompetitive inhibition
inhiibitory substance binds to another site on the enzyme
Explain saturation in biotransformation
Although the velocity of an enzyme reaction increases as the concentration of reactants increases there will be a point ehen all enzymes are occupied and are working as quickly as possible
What equation is used to describe saturation
Michaelis-Menten equation
V = ((VmazC)/(Km+C))
Vmax = Maximum Velocity
Km = Constant
C= Reaction Concentration
-This can be used to make various parameters earier to determine
What is a Lineweaver-Burke plot
essentially its the inverse of the Michaelis-Menten equation (1/V vs 1/S)
True or False: Biotransformation reactions can enhance elimination, detoxification, sequestration, redistribution and activation
True
