College aantekeningen
Lecture Notes Biomedical Sciences (BSc) BB3733 Molecular Pharmacology and Toxicology
- Vak
- Instelling
- Boek
Lecture Notes BB3733 Molecular Pharmacology and Toxicology at Brunel University
[Meer zien]Voorbeeld 4 van de 53 pagina's
Voorbeeld 4 van de 53 pagina's
In winkelwagen
In winkelwagen
Gekoppeld boek
Titel boek:
Auteur(s):
- Uitgave:
- ISBN:
- Druk:
Meer samenvattingen voor studieboek
-
A summary of benzodiazepines and their uses to treat CNS disease
-
Samenvatting Pharmacology and Nutrition
-
Stem Cells Sample Essays
Verkoper
Volgen
eunicebediako_
Ontvangen beoordelingen
Voorbeeld van de inhoud
BB3733 Molecular Pharmacology & ToxicologyIntroduction
Biochemistry Revision
- The concept of biochemistry is that all pathways interact with each other at a certain point,
so if you inhibit one there is going to be an effect elsewhere.
- A single pathway is built up by individual steps
- For a pathway to happen, there has to a negative change in free energy. There are some
steps in the pathway that are energetically expensive, so they consume energy in order for
the steps to happen. But there are also steps where there is a negative change in free
energy. As long as the overall pathway has a negative change in free energy, then the
pathway will occur in the body.
- Metabolism is facilitated by a common energy currency. The currency of free energy is ATP.
o ATP is a highly accessible molecule. It acts as a free energy donor in most energy
requiring processes
o ATP is an energy rich molecule. It has two phosphoanhydride bonds
- When ATP is hydrolysed, there is a negative change in free energy. Often ATP is hydrolysed
alongside a pathway in order to provide enough energy to drive the reaction. When a
reaction that is energetically unfavourable (positive change of energy) is coupled to ATP
hydrolysis, the reaction will occur spontaneously.
- ATP can be made easily by the hydrolysis of other molecules which drive the reaction. You
don’t want your main source of energy in the cell to be energetically unfavourable.
- Metabolism is regulated through control of:
o Amounts of enzymes
Rate of synthesis and degradation
o Catalytic activities
Reversible allosteric control/feedback inhibition
Reversible covalent modification
o Accessibility of substrates
Flux – rate of release
- Activated carries are molecules that can be split to release free energy. They are:
o Carries of electrons for oxidation of fuel
Fuel molecules transfer electrons to special carriers
Nicotinamide adenine dinucleotide (NAD+)
o The transfer of electrons helps drive the reaction
Flavin adenine dinucleotide (FAD)
o Carriers of electrons for reductive biosynthesis of molecule
o Carriers of two-carbon fragments
- The end product of glucose depends on the level of oxygen. Complete oxidation produces
oxygen, whereas incomplete oxidation produces lactate
- Glycolysis is important because it degrades glucose to provide ATP. It also provides the
building blocks for synthetic reactions. Irreversible reactions include the following enzymes:
hexokinase, phosphofructokinase (PFK) and pyruvate kinase
- Phosphofructokinase (muscle)
o Most important control site in glycolysis
o Inhibited by high levels of ATP, which bind to a separate site that is distinct from the
catalytic site
o ATP binding lowers the enzyme’s affinity for fructose 6-phosphate (substrate)
o PFK is also inhibited by a drop in pH (in muscle in response to lactic acid)
- Hexokinase
, o Inhibited by glucose 6-phosphate
o Inhibition of PFK also leads to inhibition of hexokinase
- Pyruvate kinase
o Catalyse the 3rd irreversible step
o Allosterically inhibited by ATP and alanine
o Activated by fructose 1,6-bisphosphate
- Phosphofructokinase (liver)
o Regulation with respect to ATP is the same as muscle
o Low pH is not a signal for regulation
o Regulated by citrate through ATP
o Liver glycolysis responds to changes in blood glucose through fructose 2,6-
bisphosphate and a feed-forward mechanism
- The Citric Acid Cycle produces NADH and FADH 2 as electron carriers that go into the electron
transport to produce ATP. There is also the production of GTP
- The citric acid cycle is the final common pathway for oxidation of all fuel molecules.
- The transition of electrons across the membrane drive the synthesis of ATP. Drugs could
affect electron transport by opening a channel that causes the protons to flow through the
wrong side → no protein gradient. The conversion of ADP to ATP does not happen and the
cell will heat up.
,General concepts in toxicology
Elements of toxicology
- Toxicology is defined as the science that deals with poisons and their effects
- A toxin/poison is any substance that causes a harmful effect, either by accident or design,
when administered to a living organism
- The passage of a chemical through the body is by ADME
o Absorption
Occurs via ingestion (eating), inhalation (breathing) and dermal absorption
(through the skin)
Chemicals cross the cell membrane by diffusion. Diffusion is continuous until
an equilibrium is reached
Passive diffusion
o Non-polar chemicals (lipid soluble) diffuse down the
concentration gradient
Facilitated diffusion
o Polar chemicals (water soluble) diffuse down the
concentration gradient by channels
Active transport → main entry of toxins and drugs into the body
o Polar chemicals diffuse across the membrane with no need
of a concentration gradient. This requires ATP.
o Distribution
Blood flow determines which organs receive drugs/toxins first. Tissues that
have a higher degree of perfusion have a much higher blood flow rate than
the tissues that have a lower degree of perfusion
Anything that enters the body is going to the lungs, liver and heart first and
then it will diffuse into other tissues
o Metabolism
Xenobiotic metabolism is the metabolism of any chemical interacting with
an organism which does not occur in natural metabolic pathways of that
organism
Drugs are metabolised via the pathways that are already in the body using
the same set of enzymes.
The overall effect of the metabolism of xenobiotics is to increase their water
solubility. This helps with excretion → urine.
The greatest site of metabolism is the liver
o Excretion
Active transport aids in the excretion of non-polar chemicals. Therefore,
there are a lot of transport protein pumps that are used in excretion →
particularly rich in the kidneys.
Examples; P-glycoprotein (P-gp), multi-drug resistance protein
(MDR). A lot of tumours have a high level of these pumps in their
cells to pump things out.
These are the four main elements of toxicology
, Dose-response relationships
- Whatever the compound is, as the dose increases so will the effect of the compound. There
will become a point where that compound no longer has an effect
- Dose-response relationships are used to find:
o Toxicity – is there a toxic effect? Does increase in dose also increase toxic effect?
o LD50 – median lethal dose. The dose that is responsible for killing 50% of the
population within your study. The effect, however, could be delayed
o Types of toxicity
Direct vs indirect
Local vs systemic
Immediate vs delayed/accumulative
Reversible vs irreversible
Graded (different concentrations lead to different responses) vs all-or-
nothing (there is a definite end point)
- Dose-response relationships make us assume that
o The toxic response is a function of the concentration of the compound at the site of
action → a greater effect will happen when there is an increase in toxic compound-
receptor complexes.
Reversible and irreversible reactions may give rise to different types of toxic
responses
Reversible Irreversible
Low concentrations of occupancy Single interaction will theoretically
of receptors may not produce a be sufficient to elicit a response
toxic response because once that toxin is bound, it
is permanently bound
There is a threshold below which There may not be a ‘no-effect’ level
there is a ‘no-effect’ level
Response may be short Length of response is dependent on
the turnover of the toxin-receptor
complex
Length of response depends on the Repeated or continuous exposure
concentration allows a cumulative effect to build
up
Repeated or continuous low level
exposure may also have no
measurable effect
o The concentration at the site of action is related to the dose administered
The rate of absorption, metabolism, distribution and excretion will affect the
dose that is available in the body. Therefore, compound concentration is not
always directly proportional to the dose.
Relationship between dose and the concentration of a compound at its site
of action is a factor in considering the magnitude of the response and the
‘no-effect’ level
o The response is causally related to the compound
It is not always a direct effect of the toxic compound
Not necessarily an appropriate measure of response, e.g. lead inhibition of
aminolaevulinic acid dehydrase (enzymes in production of haemoglobin),
the amount of enzyme inhibition is not necessarily in proportion to the
response.
Voordelen van het kopen van samenvattingen bij Stuvia op een rij:
Verzekerd van kwaliteit door reviews
Stuvia-klanten hebben meer dan 700.000 samenvattingen beoordeeld. Zo weet je zeker dat je de beste documenten koopt!
Snel en makkelijk kopen
Je betaalt supersnel en eenmalig met iDeal, creditcard of Stuvia-tegoed voor de samenvatting. Zonder lidmaatschap.
Focus op de essentie
Samenvattingen worden geschreven voor en door anderen. Daarom zijn de samenvattingen altijd betrouwbaar en actueel. Zo kom je snel tot de kern!
Veelgestelde vragen
Wat krijg ik als ik dit document koop?
Je krijgt een PDF, die direct beschikbaar is na je aankoop. Het gekochte document is altijd, overal en oneindig toegankelijk via je profiel.
Tevredenheidsgarantie: hoe werkt dat?
Onze tevredenheidsgarantie zorgt ervoor dat je altijd een studiedocument vindt dat goed bij je past. Je vult een formulier in en onze klantenservice regelt de rest.
Van wie koop ik deze samenvatting?
Stuvia is een marktplaats, je koop dit document dus niet van ons, maar van verkoper eunicebediako_. Stuvia faciliteert de betaling aan de verkoper.
Zit ik meteen vast aan een abonnement?
Nee, je koopt alleen deze samenvatting voor $7.16. Je zit daarna nergens aan vast.
Is Stuvia te vertrouwen?
4,6 sterren op Google & Trustpilot (+1000 reviews)
Afgelopen 30 dagen zijn er 80796 samenvattingen verkocht
Opgericht in 2010, al 14 jaar dé plek om samenvattingen te kopen
Laatst bekeken door jou
