Unit 2 Flashcards
What is cell metabolism and what are some of the activities it is responsible for?
This is a chemical process which converts carbohydrates, fats, and proteins into the energy needed for cellular functions such as muscle contraction, membrane transport and the synthesis of enzymes, hormones, and other macromolecules.
What are the predominant functions of the plasma membrane?
- To act as a a barrier to prevent general ingress/egress of material, thus preserving the cell’s status as an individual unit.
- To control movement of desirable material into the cell and the expulsion of waste material and secretions out of the cell, without breaching the barrier.
- For the receptors of the membrane to bind with specific chemical messengers, changing the activities within the cell.
- To allow physical connections of other structural components such as the joining of cells to form tissues.
How does the cell membrane regulate movement and selectivity?
Hydrophobic small molecules and gases like oxygen and carbon dioxide cross membranes rapidly, whilst small polar molecules pass through membranes more slowly. It also restricts the diffusion of highly charged molecules (such as Na+,K+,Ca2+,Cl-) and large molecules such as sugars and amino acids.
What are the two types of passive transport?
Diffusion: Spontaneous movement of a membrane permeable substance across the membrane, down the concentration gradient from an area area of high concentration to an area of low concentration.
Facilitated Transport: The movement of a membrane impermeable substance across the membrane via transporters, down the concentration gradient.
What are two types of active transport?
Primary Active Transport: The transport protein contains an ATPase which hydrolyses ATP to generate the energy required for transport.
Secondary Active Transport: There is no direct coupling of ATP with the transporter. The transporter makes use of an existing difference in electrochemical potential between cell and fluid.
How does concentration gradient affect diffusion across a membrane?
The greater the concentration gradient, the faster the rate of diffusion. This is when water moves from an area of high concentration to an area of low concentration by osmosis.
How does surface area affect diffusion across a membrane?
As the surface area of the membrane increases, the rate of diffusion also increases, as there is more space for molecules to diffuse across the membrane. This also means the shorter the distance (thickness of the membrane) the substance has to move, the faster the rate of diffusion.
How does molecular size affect diffusion across a membrane?
The smaller the molecule is, the easier the movement of the molecule through a membrane by passive diffusion.
How does state of ionisation affect diffusion across a membrane?
Only lipid-soluble, non-ionised form of the drug readily diffuses across the membrane.
Compare the solubility of polar and non-polar and ionised and non-ionised molecule.
Polar molecules are more soluble than non-polar molecules and ionised molecule is more soluble than the unionised form. This is because the molecules ability to dissolve in water depends on the structure and their ability to form either hydrogen bonds or ionic bonds.
Based from the structure how can hydrophobic and hydrophilic molecules be identified?
The presence of a polar or charged functional group means that the molecule is hydrophilic and the absence of these means that it is hydrophobic.
How does the solubility of a weakly acidic and weakly basic drug differ when the pH of the water is increased and when it is decreased?
The solubility of a weakly acidic drug will decrease when the pH of the water decreases and the solubility of a weakly basic drug increases.
The solubility of a weakly acidic drug will increase when the pH of the water increases and the solubility of a weakly basic drug decreases with a decrease of the pH of the water.
Compare the solubility of hydrophobic and hydrophilic molecules.
Hydrophobic molecules have low water solubility but prefer to dissolve in an organic lipophilic solvent and hydrophilic molecules have high water solubility but low solubility in an organic solvent.
What is partition coefficient P and what are the factors considered for the value of P?
P is the measure of the lipophilic character of a substance and depends on molecular properties such as polarity and molecular size and shape. It is the ratio of the amount of solute and solvents used. The value of p is temperature dependent and pH independent.
What condition is considered when measuring P or logP?
P or logP must be measured under pH conditions where the molecule is effectively in the unionised state. This means for a weak acid it will be a low pH (at least 3 pH units below the pKa) and for a weak base it will be a high pH (at least three pH units above the pKa).
What is Distribution Coefficient D (or logD) and what does the value depend on?
This is the measure of the total amount of the molecule dissolved in the aqueous and organic solvents. It gives the relative solubility of a molecule at pH values where the molecule is partially ionised. The value of D depends on the pH of the aqueous phase.
Describe the structure and function of cytoskeleton.
This is the cells structural support, influencing the shape, strength and flexibly of the cell as a whole and the motility of the organelles within the cell. It is made up of a variety of proteins such as actin and tubulin.
Describe the function of flagella and cilia cells.
Flagella provides the motion for sperm motility through their waving motion. However, cilia is used to move material such as a mixture of mucus, pollen and dust in the lungs along and out of the body.
What is the function of ribosomes?
These are small organelles which come together for protein synthesis, where mRNA is translated to protein.
Describe the structure and function of endoplasmic reticulum.
These are a network of membranes which are responsible for the synthesis and storage of proteins, carbohydrates and lipids, the transportation of molecules within its enclosure and the detoxification of dangerous material. They are made up of a series of tubes and chambers (cisternae).
What are the functions of rough endoplasmic reticulum?
- Receives newly manufactured protein chains from ribosomes and converts to secondary/tertiary structures.
- Modification of proteins into glycoproteins.
- Packaging of proteins/glycoproteins into transport vesicles to be sent to Golgi apparatus.
What is the function of smooth endoplasmic reticulum?
- Synthesis of phospholipids and cholesterol for endoplasmic reticulum, nuclear membrane & Golgi apparatus.
- Synthesis of steroid hormones, including sex hormones.
- Synthesis of storage of triglycerides and glycogen.
- Detoxification of drugs and alcohol.
What is the function of Golgi apparatus?
Packages cellular material for:
* Releases outside the cell via exocytosis. This allows hormones, mucins and other secretory products are sent directly to the cell membrane where vesicle fuses with the barrier and contents are released not the extracellular fluid.
* Maintenance of the cell membrane -vesicles fuses with the membrane, delivering phospholipids & various proteins.
* Enzymes into lysosomes.
What are lysosomes?
Vesicles that engulf and digest their targets to clear damaged organelles, invading bacteria and viruses or other organic waste.
What is the function of peroxisomes?
They are a group of digestive vesicles, responsible for the digestion of large fatty acids and are the site of B-oxidation. Large amounts of peroxisomes are found in cells involved in lipid metabolism.
What is the function of mitochondria?
These organelles are responsible for energy generation and large amount of these are found cells with a large energy requirement.
What is the function of nucleus?
They contain the vast majority of cells DNA and is the largest organelle. It is surrounded by a double membrane known as the nuclear envelope which includes pores that allow ions and small molecules to pass but keeps larger molecules outside and the DNA inside.
What is the difference between prokaryotic and eukaryotic cells? Provide examples of each type.
The main difference is that prokaryotic cells do not have any membrane bound organelles, most notably a nucleus. Eukaryotic cells include plant and animal cells whereas prokaryotic cells include bacteria cells.
Explain meiosis
This is the division of cells where the daughter cells are not identical. This is when cells go from being diploid (2 copies of each chromosomes) to being haploid (1 copy of each chromosome) to form gametes which contain half the genetic material of the parent cell. During sexual reproduction a sperm and ovum combine to form a new diploid cell, which grow to become a new organism.
What is sickle cell anaemia?
This is a condition which causes red blood cells to be more rigid and mis-shaped, making it harder for the red blood cells to move through smaller blood vessels. This causes painful ischemia (restricted blood flow) and can also result in organ damage. This condition is caused by a single substitution mutation in the HBB haemoglobin gene.
What is the difference between recessive inherited disorder and autosomal dominant disorder?
Recessive inherited disorder is when a healthy version of the gene will make up for the faulty copy and therefore if you have 1 good and 1 faulty copy of the gene you will be a carrier but wont have the disorder. Autosomal dominant disorder is when the faulty copy will still cause the disorder.
What does insertion or deletion cause and what is the difference between them?
This causes a frame-shift where every nucleotide beyond the mutation has been shifted along, and so all the subsequent codons will be read incorrectly, causing the resulting protein to be completely incorrect. Insertion is when an additional nucleotide has been added to the sequence whereas deletion is when a single nucleotide has been removed.
How does Down syndrome occur?
This occurs when a person has an extra copy of chromosome 21 which is usually caused by a fault during meiosis where one of the gametes carried an extra copy of chromosome 21. This could also be caused by the loss of an entire chromosome such as turner syndrome where they only have X chromosome caused by a fault during meiosis in one of the parents.
What is cystic fibrosis?
This is a recessive inherited disorder which results from the improper transport of chloride causing build up of thick mucus in the lungs, creating difficulty in breathing.
Give three types of molecules used in biological communications.
- Endocrine Factors: Released from cells and enter circulation.
- Paracrine Factors: Released from cells and have local site of action.
- Autocrine Factors: Released from cells and act on the same cells.
How does potential difference occur?
This occurs due to the uneven distribution of ions inside and outside of the cell. There is a high concentration of sodium and chloride ions outside of the cell and high concentration of potassium and various anions inside the cell, creating an electrochemical gradient across the cellular plasma membrane.
What is resting membrane potential?
This is the electrical charge difference across the membrane where the inside of the neuron is more negative and the outside is more positive, creating a resting membrane potential of -70mV.
What is equilibrium potential and what is the equilibrium potentials for potassium, sodium and neuron?
This is the point at which there would be no net movement of the ion across the membrane. The equilibrium potential for potassium is approximately -80mV, for sodium it is +60mV and a neuron is -70mv.
What are two ways an ion channel can be opened?
- Ligand-gated ion channels: contain binding sites where specific substances (ligand) can attach to the ion channel causing it to open.
- Voltage-gated ion channels: sensitive to the membrane potential of the cell, therefore channel will be closed at resting membrane potential and open when membrane potential rises as it will cause the protein making up the channel to shift.
What is the functions of each part of a neuron?
Dendrites: Receive input from other neurons.
Cell body: Includes nucleus endoplasmic reticulum and mitochondria as well as the organelles found in cells - also known as soma.
Axon: Main conduction unit, carries information in the form of electrical signal known as the action potential. Axon meets the cell body at the axon hillock and can be myelinated/unmyelinated.
Axon terminals: The output region, release of neurotransmitter.
What is threshold and what causes it?
Threshold is when the membrane potential reaches -55mV which is the minimum energy required for generating an action potential. This occurs when the ligand-gated ion channels are activated and when the local potential is strong enough it will reach the threshold. This causes the voltage-gated channels to open and cause further depolarisation of the membrane and initiating an action potential.
What is an action potential caused by?
This is caused by the opening and closing of voltage-gated sodium channels, potassium channels and sodium-potassium ATPase.
What is depolarision of the membrane?
This is the flow of sodium ions into the cell down its chemical gradient and its electrical gradient until it reaches its reversal potential of +30mV when the sodium channels close.
What is repolarisation of the membrane?
This is when the voltage-gated potassium channels open, allowing potassium ions to flow out of the cell down its chemical gradient and its electrical gradient, bringing the membrane potential back towards the equilibrium potential of -80mV.
What is hyperpolarisation of the membrane?
This occurs at the end of the action potential when the membrane potential goes slightly lower than the usual resting potential and therefore an action potential cannot be achieved. This occurs due to some potassium ion channels remaining open.
What is refractory period and what are the two types?
This is when the neuron cannot fire another action potential. There are 2 types where the absolute refractory period occurs immediately after the action potential and the voltage-gated sodium channels are still deactivated. The other type is the relative refractory period where the voltage gated sodium channels are now ready to generate another action potential but the membrane is still hyperpolarised as the membrane potential is still lower than the normal RMP, a bigger stimulus is required to reach threshold.
Give a summary of the phases of an action potential.
- Cell started at RMP. A large stimulus is applied to reach the threshold membrane potential (-55mV) which will initiate an action potential -sufficient voltage gated sodium channels open to cause a large depolarisation.
- Depolarisation to a peak of +30mV known as equilibrium potential occur for Na+.
- Repolarisation to -90mV occur, overshoot at the end of this is known as hyperpolarisation.
- RMP is restored by Na-K ATPase, pumps 3 Na+ for every 2K ions back in.
Explain the process of continuous propagation?
This is the mechanism by which the action potential is propagated along the unmyelinated neurons. The Na+ ions flow cause depolarisation to such further opening of the Na channels. The action potential spreads in one direction due to the refractory period as Na channels which have been opened, close for a period before being triggered again.
What is myelin sheath formed from what are the benefits?
The myelin sheath is formed by glial cells (oligodendrocytes in the central nervous system, Schwann cells in the peripheral nervous system). This supports saltatory conduction where the myelin sheath acts as an insulator to prevent the change in membrane potential in the axon, allowing signal to travel faster. Action potential is generated at each nodes of Ranvier and therefore skips the length of the axon rather than depolarising the entire membrane surface.
What is Multiple Sceloris (MS) and Guillain-Barré syndrome?
These are both autoimmune disorders, with MS involving damage to myelination in the central nervous system and Guillain-Barré syndrome involves damage to myelination in the peripheral nervous system. The systems to both of these is due to the action potential being unable to travel correctly along the axon due to the damage.
What are the factors affecting the speed of conduction in neurons?
- Myelinated neurons conduct faster than non-myelinated neurons.
- Axons with greater diameter conduct faster than thinner axons.
Explain the process of paracrine signalling?
Action potential travels along the presynaptic neuron and reaches the synapse. This causes a neurotransmitter to be released into the synaptic cleft. The neurotransmitter then binds with receptors on the post-synaptic cell, causing a response.
What are the principles of synaptic transmission between neurons?
- Depolarisation opens voltage-sensitive Ca2+ channels & neurotransmitter release at the axon.
- Release of neurotransmitter activates receptors.
- Opening of ligand-gated ion channels cause depolarisation: excitatory post synaptic potentials.
- Depolarisation can spread along neuronal membranes and if threshold potential is reached at the axon hillock then the neuron can fire.
What are receptors and what are there functions?
These are membrane proteins that can act as either transducers which respond to external stimuli or they can operate as transporters where they bring molecules into the cell interior by the process of receptor-mediated endocytosis.
What is the function of ionotropic receptors?
These receptors are part of the ligand-gated ion channel protein and activation results in conformational changes in the channel protein, allowing specific ions to pass through by facilitated diffusion along the concentration gradient. These ions could be Na+, K+ or Cl-. This type of receptor results in fast transmission.
What is the difference between excitatory postsynaptic potential and inhibitory postsynaptic potential?
Excitatory postsynaptic membrane is when ligand-gated sodium channels cause an increase in the local membrane potential through neurotransmission, making the postsynaptic membrane more positive as it is closer to threshold. Inhibitory postsynaptic membrane is when the ligand-gated chloride channels open, making the postsynaptic membrane more negative as it is further from the threshold.
What is the function of metabotropic receptors (G protein-coupled receptors GPCR)?
This requires receptor protein in the membrane to be coupled to the effector mechanism via G protein. The agonist molecule combines with the receptor proteins in the membrane and causes activation of a membrane-associated enzyme via the activated G protein. This leads to formation of intracellular ‘second messengers’ where cellular effect is much slower. This type is used in slower neurotransmission processes.
What are the 2 major examples of metabotropic receptor system?
- Adenylate Cyclase: Activated via the G protein when the ‘first messenger in the ECF combines with the receptor.
- Cyclic AMP System: Activates cAMP-dependent protein kinase which initiates the cellular response when the ‘second messenger’ cyclic AMP(cAMP) is generated inside the cell.
What is the process of calcium-mobilising receptors?
This process releases intracellular Ca2+ from the endoplasmic reticulum which is an important mediator of cell activity, responsible for initiating muscle contraction, secretion, release of neurotransmitters & other.
What is the process of kinase-linked receptors?
This enzyme catalyse the transfer of phosphate groups from a donor molecule to a specific target molecule and the process is involved in regulation of growth, differentiation and responses to metabolic signals. The receptor protein has an extracellular domain to bind the ligand and intracellular enzymatic (kinase) domain.
What is the process of nuclear (intracellular) receptor ?
Intracellular receptor proteins bind lipid-soluble ligands and the complex then binds to DNA and regulate gene transcription. This results in an increased synthesis of specific proteins. Responses are usually long-lasting & remain long after agonist binding
Explain the difference in binding between steroid hormone and thyroid hormone.
Steroid hormones diffuse through the membrane lipids and bind to receptors in cytoplasm or nucleus whereas thyroid hormones enter the cytoplasm and bind to receptors in the nucleus to activate specific genes and also bind to receptors on the mitochondria and accelerate ATP production.
What is the difference between agonist and antagonist?
Agonists mimics the action of endogenous ligand and initiate cellular response. However, antagonists binds to a receptor without activating it but decrease the receptors ability to be activated by another agonist. This is achieved by the drug blocking the action of endogenous ligand. They have affinity but not efficacy.
What is affinity (1/kD)?
This is a measure of how strongly a drug binds to a receptor where kD corresponds with the concentration of drug required to occupy 50% of the receptors. The higher the affinity the lower the kD.
What is intrinsic efficacy?
The ability of an agonist to bound to a receptor and initiate a cellular response by ensuring coupling the agonist-receptor complex with the transduction system.
Compare a molecule that has high affinity but low efficacy and low affinity but high efficacy.
- A molecule with high affinity but low efficacy is highly likely to react with a receptor but not cause much response once it has bound.
- A molecule with low affinity but high efficacy will have limited ability to interact with a receptor but when it does it causes a large response.
What is the difference between full and partial agonist and the effect f the presence of a partial agonist by itself and with a full agonist?
Full and partial agonist depends on intrinsic efficacy as full agonists have high intrinsic efficacy whereas partial agonists have low intrinsic efficacy. A partial agonist by itself will act as an agonist as it does have some efficacy however with the presence of a full agonist they will both be trying to bind to the free receptors so the partial agonist will act as an antagonist and reduce the effect of full agonist.
What is inverse agonists?
An inverse agonist possesses both affinity and efficacy, but the efficacy is a negative property rather than a positive property.
What are the 2 types of antagonists?
- Competitive antagonists bind to the same site as the agonist and so compete for this binding site.
- Non-competitive antagonists binds elsewhere on the receptor in such a way that reduces the ability of the agonist to bind or cause a response.
How can competitive antagonists be reversible and irreversible?
A reversible antagonist binds non-covalently to the receptor.
An irreversible antagonist binds covalently to the receptor and cannot be displaced by either competing ligands.
What is physiological antagonism?
This is when 2 agonists act on their own receptors induce opposing effects in the cells/tissue. This is important in the physiological regulation of body functions such as motility of the intestines and rate of the heart, where the neurotransmitter acetylcholine, released from the parasympathetic nerve, increases gut motility & decreases heart rate, whereas noradrenaline released from the sympathetic nerves decreases gut motility & increases heart rate.
What is the difference between chemical antagonism and pharmacokinetic antagonism?
Chemical antagonism is when 2 drugs interact in solution, causing a loss of biological activity when administered together.
Pharmacokinetic antagonism is when 1 drug affects absorption, distribution, metabolism and excretion of another.
What is the main excitatory and inhibitory neurotransmitter in the brain?
Main excitatory neurotransmitter: glutamate
Main inhibitory neurotransmitter: GABA
How does drugs affect synaptic transmission?
Synthesis- Block neurotransmitter production (inhibit enzymes, alter precursors).
Storage- Prevent neurotransmitters from entering or staying in vesicles.
Release- Block Ca²⁺ channels to stop neurotransmitter release.
Receptor Activation- Act as agonists/antagonists or alter presynaptic control.
Inactivation/ Reuptake- Inhibit breakdown enzymes or block reuptake
What is acetylcholinesterase inhibitors and what effect does this have on the synaptic cleft?
These are nerve agents which prevent the breakdown of acetylcholine. The continued presence of acetylcholine in the synaptic cleft desensitises the receptors, and acetylcholine signalling no longer functions. This will cause neurological symptoms, and can be fatal due to respiratory symptoms.
What is the process for dopamine synthesis, neurotransmission and reuptake?
- Tyrosine is converted to L-DOPA by tyrosine hydroxylase.
- L-DOPA is converted to dopaminergic by DOPA Decarboxylase.
- Dopaminergic can then be loaded into synaptic vesicles by a vesicular monoamine transporter (VMAT).
- After being released into the synapse, dopamine is then transported back into the presynaptic neuron by dopamine transporter (DAT).
- Dopamine is broken down by monoamine oxidase (MAO) enzymes.
What are the 4 major dopaminergic pathways in the brain?
- Mesolimbic pathway: neurons project from the ventral tegmental area (VTA) to the ventral striatum.
- Mesocortical pathway: projects from the VTA to the prefrontal cortex.
- Nigrostriatal pathways: projects from the substantia nigra (SN) to the dorsal striatum. Involved in motor control and Parkinson’s disease
- Tubero-infuni
What is Parkinson’s disease and what is the treatment used?
- Mesolimbic pathway: neurons project from the ventral tegmental area (VTA) to the ventral striatum.
- Mesocortical pathway: projects from the VTA to the prefrontal cortex.
- Nigrostriatal pathways: projects from the substantia nigra (SN) to the dorsal striatum. Involved in motor control and Parkinson’s disease
- Tubero-infundibular pathways: involved in hormone secretion.
Compare the inhibitors serotonin reuptake and serotonin-norepinephrine reuptake and monoamine oxidase.
What is GABA and what is the difference between GABAA and GABAB receptors?
GABA is an amino acid neurotransmitter & is the main inhibitory neurotransmitter in the brain.
GABAA receptors are ionotropic, whereas GABAB receptors are metobotropic.
What is the effect of z-drugs and alcohol on GABAA receptors?
Z-drugs causes the channel to open more frequently.
Alcohol causes the channel to remain open for longer.
What is a hormone?
A compound (chemical messenger) which is secreted by one cell and travels through the circulatory system to affect the activities of the cells in another part of the body.
What are neurohormones and autacoids or local hormones?
Neurohorhomes: Hormones released by neurons
Autacoids or Local Hormones: Chemical messengers that have paracrine e.g. histamine
What are the three groups of hormones?
- Amino acid derivatives
- Peptide hormones
- Steroid hormones
All based on their chemical structure
Explain the secretion, distribution and mechanism of hormone action?
- Released near capillaries for quick bloodstream entry.
- Circulate freely or bound to carrier proteins.
- Free hormones last 2 mins-1 hr.
- Inactivated by binding to target cells, breakdown in liver/ kidneys, or plasma enzymes
Give facts about thyroid hormone function?
- Amino acid-derived but doesn’t bind to membrane receptors.
- Enters cells via transport mechanisms.
- Binds nuclear & mitochondrial receptors, affecting DNA transcription & ATP production.
- Regulates metabolic activity.
- T4 is the most prescribed drug in England and Wales.
What is the difference between potency and clinical efficacy (maximum effect)?
Potency refers to the concentration or amount of drug required to produce a defined effect whereas clinical efficacy judges the therapeutic effectiveness of the drug in humans.
What is meant by drug variability?
Differences in magnitude of response among individuals in the same population given the same dose of drug, or within an individual given the drug on different occasions.
What are the factors contributing to drug variability?
- Age
- Weight
- Sex
- Genetic factors
- State of health / disease
- State of hydration and acid/base balance
- Liver / kidney function
- Other drugs
- Compliance
- Placebo effect
- Tolerance / tachyphylaxis
What is tachyphylaxis?
This is when the responsiveness to a drug diminishes rapidly after initial administration or during continued administration.
What is drug tolerance?
This is a gradual loss of response to a drug and therefore a higher dose is required to achieve the original response.
What is drug desensitisation?
This could be either tachyphylaxis or tolerance depending on the speed of response to the drug.
What are the possible causes of tachyphylaxis and tolerance?
- Changes in receptors
- Loss of receptors
- Increased metabolism
- Physiological adaptation
- Depletion of mediators
- Cellular extrusion of drugs
What is drug dependence?
This refers to the situation where the person has developed a physical or physiological requirement for the drug in order to avoid precipitation of withdrawal symptoms if administration of the drug is not repeated.
How can receptors become super sensitive to stimulation by agonists?
- A blockage of a receptor population from access to agonist molecules as a result of exposure to high affinity antagonists, once antagonist is removed it is more sensitive to the agonist.
- Receptor is deprived of agonist.
How can a receptor become deprived of agonist?
- Increased coupling of receptors to cellular effect mechanisms.
- Increased numbers of receptors in the membrane.
- Translocation of receptors out from the neuromuscular endplate to the remainder of the sarcolemma.
What is bioavailability?
Term used to indicate the fractions of administered drug reaching the systemic circulation as intact drug.
This can be found from plasma levels of the drug following oral administration & comparing them with levels following direct IV injection (bioavailability=100%).
