TOX 2000 Biomedical Toxicology
Exam-Graded A
Hypernatremia - ANSWER-dehydration; exccess NaCl in the blood
linked to infant salt poisoning: sub sugar for table salt, administer salt as emetic, baking
soda for indigestion in 3 year olds
Hyponatremia - ANSWER-overhydration; low solute concentration outside of cell
fluid shift due to osmosis causes swelling
can interrupt blood flow: cerebral edema, CNS dysfunction
Toxicant Biological Cascade - ANSWER-1. Toxicant
2. Delivery
3a. interaction with target
3b. alteration of biological environment
4. cellular dysfunction or repair or repair failure
5. TOXICITY
Routes of Uptake, 4 - ANSWER-1. Ingestion: can be modified by enzymes, pH,
microbes, before absorption
2. Respiration: air born toxicants can be exhaled before absorption
3. Skin: stratum corneum provides barrier to external toxicants
4. Injection: due to drug use, or abrasion
Barriers to Uptake, 2 - ANSWER-1. Epithelial Cells: GI tract, lungs, skin
2. Cell Membrane
Passive Diffusion - ANSWER-most common
1. difference in concentration of substance causes solute to move down concentration
gradient to establish equilibrium
2. can move through small pores or lipophilic interior
lipid soluble: diffuse through PM
water soluble: diffuse through aqueous pores
Facilitated Diffusion - ANSWER-carrier mediated, faster, larger molecules can be
moved
1. solute carried by trans membrane carrier with conc. gradient
2. energy independent
3. enhance transport by 50, 000
Active Transport - ANSWER-independent of conc. gradient
,requires ATP\energy source
substrate specific
rate limited by number of carriers
Endocytosis - ANSWER-engulfed substance and section of membrane move into
interior of cell
> process used in phagocytosis\pinocytosis
> stimulated by interaction of toxin and surface receptors
Intercalation - ANSWER-the reversible inclusion of a molecule (or group) between two
other molecules (or groups); comes from chemical exposure
Toxin:Target Selectivity - ANSWER-targets are usually proteins, lipids, enzymes,
nucleic acids
> all endogenous molecules
> typically involved in critical pathways
> need to be susceptible to toxic insult
> need to be accessible to toxicant
> need to be reactive with toxicant
Toxin:Target Reactions, 5 - ANSWER-1. Noncovalent binding
2. Covalent Binding
3. Hydrogen Abstraction
4. Electron Transfer
5. Enzymatic Reactions
1. Noncovalent Binding - ANSWER-reversible
lock and key inhibitors
typically with membrane receptors\enzymes
2. Covalent Binding - ANSWER-irreversible, permanent attraction to nucleophilic
centers in DNA and proteins
3. Hydrogen Abstraction - ANSWER-neutral free radicals abstract H+ from target,
producing reactive free radicals
4. Electron Transfer - ANSWER-Oxidation of ions within proteins, altering function
ex. Fe2+ to Fe3+ in Hb, limits O2 affinity
5. Enzymatic Reactions - ANSWER-if toxin is protein:
antagonists or agonists
can catalyze reactions in cell, leading to altered function
Toxin:Target Outcomes, 3 - ANSWER-1. Dysfunction
2. Destruction
3. Neoantigens
, 1. Dysfunction - ANSWER-> act of target mimics endogenous ligands, dioxins
> inhibition of target, microcystin
> alteration of target conformation, thiol disruption
2. Destruction - ANSWER-> crosslinking of proteins and DNA: causes fragmentation
and ultimately degradation
> physiochemical change: lysis, trigger apoptosis, etc.
3. Neoantigens - ANSWER-reactive intermediates formed
> covalently bind toxicant with targets released from cells
Affinity - ANSWER-Strength of binding between toxin and target
Dissociation constant, Kd: toxins affinity for a given receptor
concentration of toxin required in solution to
achieve 50% occupancy
Agonists - ANSWER-Alter physiology of cell by binding to receptor, and prevents
anything else from binding
Partial: does not produce maximal effect when all receptors are occupied
Antagonists - ANSWER-inhibit and block response of agonist
Competitive: can be overcome; competes with agonist for receptor
Noncompetitive: cannot be overcome; binds alternate site, inducing conformational
change of ligand bind site
Microcystins - ANSWER-peptide toxins produced by cyanobacteria
> hepatotoxic, enters via bile acid transport system
> specific to hepatocytes
> affect protein phosphatases PP1 and PP2A, imbalancing protein phosphorylation
> produce rash, hives, skin blisters, RT irriation, GI irritation upon contact
PP1 - ANSWER-PROTEIN PHOSPHATASE 1
involved in controlling glucose metabolism, muscle contraction, cell cycle progression,
neuronal activities, RNA splicing. If uncontrolled:
GI symptoms
Respiratory symptoms
Liver damage
protein phosphatase 1, activated by insulin via PKB => GSK3. dephosphorylates
glycogen synthase, glycogen phosphrylase and phosphorylase kinase
Exam-Graded A
Hypernatremia - ANSWER-dehydration; exccess NaCl in the blood
linked to infant salt poisoning: sub sugar for table salt, administer salt as emetic, baking
soda for indigestion in 3 year olds
Hyponatremia - ANSWER-overhydration; low solute concentration outside of cell
fluid shift due to osmosis causes swelling
can interrupt blood flow: cerebral edema, CNS dysfunction
Toxicant Biological Cascade - ANSWER-1. Toxicant
2. Delivery
3a. interaction with target
3b. alteration of biological environment
4. cellular dysfunction or repair or repair failure
5. TOXICITY
Routes of Uptake, 4 - ANSWER-1. Ingestion: can be modified by enzymes, pH,
microbes, before absorption
2. Respiration: air born toxicants can be exhaled before absorption
3. Skin: stratum corneum provides barrier to external toxicants
4. Injection: due to drug use, or abrasion
Barriers to Uptake, 2 - ANSWER-1. Epithelial Cells: GI tract, lungs, skin
2. Cell Membrane
Passive Diffusion - ANSWER-most common
1. difference in concentration of substance causes solute to move down concentration
gradient to establish equilibrium
2. can move through small pores or lipophilic interior
lipid soluble: diffuse through PM
water soluble: diffuse through aqueous pores
Facilitated Diffusion - ANSWER-carrier mediated, faster, larger molecules can be
moved
1. solute carried by trans membrane carrier with conc. gradient
2. energy independent
3. enhance transport by 50, 000
Active Transport - ANSWER-independent of conc. gradient
,requires ATP\energy source
substrate specific
rate limited by number of carriers
Endocytosis - ANSWER-engulfed substance and section of membrane move into
interior of cell
> process used in phagocytosis\pinocytosis
> stimulated by interaction of toxin and surface receptors
Intercalation - ANSWER-the reversible inclusion of a molecule (or group) between two
other molecules (or groups); comes from chemical exposure
Toxin:Target Selectivity - ANSWER-targets are usually proteins, lipids, enzymes,
nucleic acids
> all endogenous molecules
> typically involved in critical pathways
> need to be susceptible to toxic insult
> need to be accessible to toxicant
> need to be reactive with toxicant
Toxin:Target Reactions, 5 - ANSWER-1. Noncovalent binding
2. Covalent Binding
3. Hydrogen Abstraction
4. Electron Transfer
5. Enzymatic Reactions
1. Noncovalent Binding - ANSWER-reversible
lock and key inhibitors
typically with membrane receptors\enzymes
2. Covalent Binding - ANSWER-irreversible, permanent attraction to nucleophilic
centers in DNA and proteins
3. Hydrogen Abstraction - ANSWER-neutral free radicals abstract H+ from target,
producing reactive free radicals
4. Electron Transfer - ANSWER-Oxidation of ions within proteins, altering function
ex. Fe2+ to Fe3+ in Hb, limits O2 affinity
5. Enzymatic Reactions - ANSWER-if toxin is protein:
antagonists or agonists
can catalyze reactions in cell, leading to altered function
Toxin:Target Outcomes, 3 - ANSWER-1. Dysfunction
2. Destruction
3. Neoantigens
, 1. Dysfunction - ANSWER-> act of target mimics endogenous ligands, dioxins
> inhibition of target, microcystin
> alteration of target conformation, thiol disruption
2. Destruction - ANSWER-> crosslinking of proteins and DNA: causes fragmentation
and ultimately degradation
> physiochemical change: lysis, trigger apoptosis, etc.
3. Neoantigens - ANSWER-reactive intermediates formed
> covalently bind toxicant with targets released from cells
Affinity - ANSWER-Strength of binding between toxin and target
Dissociation constant, Kd: toxins affinity for a given receptor
concentration of toxin required in solution to
achieve 50% occupancy
Agonists - ANSWER-Alter physiology of cell by binding to receptor, and prevents
anything else from binding
Partial: does not produce maximal effect when all receptors are occupied
Antagonists - ANSWER-inhibit and block response of agonist
Competitive: can be overcome; competes with agonist for receptor
Noncompetitive: cannot be overcome; binds alternate site, inducing conformational
change of ligand bind site
Microcystins - ANSWER-peptide toxins produced by cyanobacteria
> hepatotoxic, enters via bile acid transport system
> specific to hepatocytes
> affect protein phosphatases PP1 and PP2A, imbalancing protein phosphorylation
> produce rash, hives, skin blisters, RT irriation, GI irritation upon contact
PP1 - ANSWER-PROTEIN PHOSPHATASE 1
involved in controlling glucose metabolism, muscle contraction, cell cycle progression,
neuronal activities, RNA splicing. If uncontrolled:
GI symptoms
Respiratory symptoms
Liver damage
protein phosphatase 1, activated by insulin via PKB => GSK3. dephosphorylates
glycogen synthase, glycogen phosphrylase and phosphorylase kinase
