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Bio 2A03 MIDTERM 1.docx

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McMaster University
Ayesha Khan

Osmosis – passive transport of water across membranes - Although water is polar, it has high permeability in membranes due to its small size - Osmosis depends on the concentration of other molecules 1. H2O concentration depends on the number of dissolved particles. Water concentration is higher when there are fewer solutes 2. Total solute concentration in solution determines osmolarity o Solution containing 1 mole of solute particles is at a concentration of 1 osmolar (1 Osm) o 1 mole of solute particles = 1 osmole o Eg. 1 M of glucose in solution = 1 osmole but 1 M of NaCl = 2 osmoles since it ionizes to Na+ and Cl- 3. The higher the osmolarity of a solution, the lower the H2O concentration 4. Osmosis occurs in the direction of higher osmolarity (or lower [H2O]). Water moves towards the more solute concentrated solution. - Note: flux can be increased by aquaporin (protein channels) - Cells are permeable to water but impermeable to many solutes - Tonicity: function of concentration of non-permeating solutes outside a cell relative to the concentration inside the cell, and it determines the behaviour of the cell place din solution 1. Isotonic – extracellular fluid has the same number of osmoles of non-penetrating solute. o Results in no change in cell volume 2. Hypertonic – extracellular fluid has a greater number of osmoles of non-penetrating solute. o Results in cell shrinking 3. Hypotonic – extracellular fluid has lower number of osmoles of non-penetrating solute o Results in cell swelling - Osmolarity: total solute particle concentration of a solution o Relates the osmolarity of a solution relative to normal extracellular fluid without regard to penetrating or non-penetrating nature of solutes  Note: a solution can be isosmotic at 300 mOsm but hypotonic due to penetrating solutes 1. Iso-osmotic – two solutions have same osmolarity. Two solutions have same solute and same water concentration. 2. Hyperosmotic – a solution whose osmolarity is higher than another. Water concentration is lower because solute concentration is higher 3. Hypo-osmotic – a solution with lower osmolarity. Water concentration is higher because solute concentration is lower Compartmentalized Transport - Vesicular transport (in an intracellular compartment) needed to transport macromolecules across the plasma membrane - Endocytosis – movement of molecules from ECF into the cell with the formation of endosomes from the plasma membrane - Forms of endocytosis: phagocytosis, pinocytosis, receptor mediated endocytosis 1. Phagocytosis (cell eating) – cell extends membrane around particle to create a large endosome, phagosome (common in WBC) o Cell engulf the particle. Once inside, the membrane of the phagosome fuses with the membrane of a lysosome forming a phagolysosome which exposes engulfed particle to degradative enzymes of the lysosome 2. Pinocytosis (cell drinking) – plasma membrane indents to form endosome around dissolved solutes 3. Receptor mediated endocytosis – plasma membrane indents to form endosome. o Specific process where proteins in the plasma membrane function as receptors that bind specific particles in ECF (binding must occur prior to endocytosis of molecules) o Vesicles are coated with clathrin proteins that form clathrin-coated pits before it becomes a clathrin coated vesicle - Exocytosis – movement of molecules from ICF into ECF with the use of secretory vesicles - Functions of exocytosis: 1. Add components to the plasma membrane 2. Recycle receptors removed from the plasma membrane by endocytosis 3. Secrete specific substances out of the cell and into the ECF - Endocytosis and exocytosis are closely balanced in the cell to maintain uniform cell size and shape Epithelial Transport: movement of molecules across 2 membranes (across entire cells) - Epithelial solute transport – movement of solutes across an epithelial cell layer o Apical membrane – facing outside environment (lumen) o Basolateral membrane – facing internal environment (interstitial fluid) - There are differing transport systems on the apical and basolateral membranes - Note: Na+ enters apical membrane via a cotransporter (secondary active) but exits via a pump (primary active) on the basolateral membrane. K+ goes into cell against a concentration gradient by primary active transport via Na+/K+ pump. K+ leaves the cell through leaky transport. - Epithelial water transport – movement of water across an epithelial cell layer via osmosis. It is dependent on the active transport of solutes to create the osmotic pressure gradient o Pumps in the basolateral membrane actively transport solute molecules into the interstitial fluid, raising the solute concentrations in the interstitial fluid. Active solute transport creates a gradient of osmotic pressure across the epithelium that drives passive water flow from the lumen to the interstitial fluid - Transcytosis – movement of macromolecules across an epithelial cell layer via vesicular transport which involves both endocytosis and exocytosis o Large molecule is taken in by endocytosis, but vesicle doesn’t fuse with lysosome. Instead vesicle travels to the opposite side of the cell and fuses with the plasma membrane to release its contents by exocytosis Colligative properties - Properties that depend on the ratio between the solutes (number of particles) and the solvent in a solution (osmolarity, vapor pressure, boiling point and freezing points) - Note: CaCl2 will melt snow/ice faster than NaCl (3 osmol vs 2 osmol) Tonicity vs. Osmolarity - Osmolarity of a solution is based on the total solute concentration (both penetrating and non-penetrating) - Tonicity of a solution is based on the concentration of non-penetrating solutes Intercellular Communication - Cell to cell communication is important for homeostasis - Intercellular communication is performed by intercellular chemical messengers: 1. Hormones: secreted from endocrine glands into the interstitial fluid where they diffuse into blood for transport to target cells in the body. Target cells are identified by the presence of receptors for the specific hormone. Cells without receptors for the hormone can’t respond to the hormone’s signal. o Slow acting o Eg. Insulin and glucose homeostasis o Special class are neurohormones eg. Vasopressin (or ADH) 2. Neurotransmitters: chemicals released into interstitial fluid from nervous system cells called neurons. They are released from the axon terminal of the presynaptic neuron to the synapse where neurotransmitters diffuse a short distance and binds to receptors on the postsynaptic cell, triggering a response o Fast acting o Eg. Acetylcholine and heart rate 3. Autocrine/ Paracrine agents: local homeostatic responses on target cell by diffusion o Autocrine – same cell o Paracrine – neighbouring cells eg. Growth factors, clotting factors, cytokines (coordinate body’s defense against infections) o Eg. ATP, NO, fatty acid derivatives (eicosanoids) Signal Transduction Pathways: detect intercellular messengers and convert them into a biologically meaningful response - 4 features of signal transduction pathways: 1. Specificity – only the signal molecule fits in its receptor. Note: can also have messenger bind to multiple receptors with different affinities 2. Amplification – 1 receptor binding can lead to 1,000,000 products 3. Desensitization/ adaptation – feedback processes causes receptor to shut off or removes it 4. Integration – outcome of integration of both receptor units. Note: signals may give opposite responses - Properties of receptors: magnitude of cell’s response depends on 1. Concentration of messenger 2. Number of receptors present 3. Affinity of receptor for messenger - Note: a single messenger can often bind to more than one type of receptor and receptors may have different affinites for the messenger - An increase in the number of receptors increases the number bound with the messenger - A higher proportion of high affinity receptors have bound messenger compared to low affinity receptors. The high affinity receptors reach saturation at a lower messenger concentration than do low affinity receptors Receptors can be intracellular (within cell – located in cytosol or nucleus): 1. Receptors bind to lipophilic messengers (easily permeate the plasma membrane) 2. Alters synthesis of a specific protein via mechanism shown in diagram 3. Act as transcription factors to transcribe new proteins - Eg. Steroids = hormones Receptors can be membrane bound (bind to lipophobic messengers because lipophobic messagers cannot permeate through plasma membrane) - 3 main types of membrane bound receptors: channel linked, enzyme linked, G-protein linked 1. Channel-linked receptors o Channel linked receptors are a type of ligand- gated channel, where ion channels open or close in response to the binding of a chemical to a receptor o Fast ligand-gated channels acts as a receptor and as a channel o This is an example of a fast channel o By binding of the messenger, this allows the channel to open quickly and briefly 2. Enzyme-linked receptors o Enzyme-linked receptors acts ass both enzyme and receptor. They are transmembrane proteins with the ligand-binding domain facing the extracellular surface and enzyme active site facing the cytosol. Enzymes are activated when a messenger binds to the receptor allowing them to catalyze 3.intracellular reactions o Most are tyrosine kinases o Binding activates tyrosine kinase activity which phosphorylates a protein on the tyrosine 1. Messenger binds to the receptor, change conformation 2. Conformation change activates tyrosine kinase 3. Tyrosine kinase catalyzes phosphorylation of intracellular protein 4. Phosphorylation of protein changes it activity by covalent regulation, bringing about a response in the target cell o Eg. Insulin receptor Why are different modes of delivery required for different prescribed hormones? Example: a steroid-based oral contraceptive (ie. Birth control pills) vs. injectable insulin (a peptide- hormone)? o The stomach has proteases o Insulin as a peptide cannot be absorbed o Lipophilic (hydrophobic) vs. lipophobic (hydrophilic) 3. G-protein linked receptor o Activates membrane proteins called G- proteins and begin a signaling cascade o G proteins can be stimulatory (Gs) or inhibitory (Gi). G proteins have ability to bind to guanosine nucleotides and have 3 subunits: a, B, y. o To activate the GPCR, the alpha subunit binds to GTP to become active. o Roles: 1. Regulates a protein channel Eg. Can open or close a slow ion channel. Channel does not act as a receptor 2. Often activates an enzyme Eg. Adenylate cyclase to produce cAMP - cAMP second messenger system: 1. first messenger binds to receptor activating stimulator G protein 2. G protein releases alpha subunit that binds and activates adenylate cyclase 3. Adenylate cyclase catalyzes conversion of ATP to cAMP 4. cAMP activates PKA (cAMP dependent protein kinase) 5. protein kinase catalyzes transfer of phosphate group from ATP to a protein 6. altered protein activity causes response in cell - Lefkowitz & Kobilka: B2 adrenergic GPCR. o Key functions in circulatory system: 1. Heart muscle contraction 2. Increase in cardiac output - First messenger – intercellular (between cell) chemical messenger which reaches the cell surface - Second messenger – intracellular (within cell) messenger produced by binding of the first messenger o Act as chemical relays from the plasma membrane to protein kinase Second Precurs Amplifier Usual action Ex of first messenger messenger or enzyme Cyclic adenosine ATP Adenylate Activate PKA Epinephrine, vasopressin, monophosphate cyclase ACTH, glucagon (cAMP) cGMP GTP Guanylate Activate PKG Atrial natriuretic cyclase DAG PIP2 Phospholipase Activate PKC Angiotensin II, histamine, C vasopressin IP3 PIP2 Phospholipase Stimulates calcium Angiotensin II, histamine, C release from intracellular vasopressin stores Calcium None None Binds to calmodulin, then Angiotensin II, histamine, activate PK vasopressin - Phosphatidylinositol second messenger system: 1. Messenger binds to its receptor, activating G protein 2. G protein release alpha subunit and binds to phospholipase C 3. Phospholipase C catalyzes conversion of PIP2 to DAG and IP3 4. DAG remains in membrane and activates PKC 5. PKC catalyzes phosphorylation of a protein which brings response in cell 6. IP3 moves to cytosol 7. IP3 triggers release of calcium from ER 8. Calcium then does either: a. Acts on proteins to stimulate contraction or secretion b. Acts as second messenger by binding to calmodulin, activating PK that phosphorylates protein that produces response in cell - Second messengers has the ability of small changes in concentration of a chemical messenger to elicit marked changes in target cells – signal amplification - Response of the cell (eg. Glycogen breakdown in liver cells): - - Adrenergic receptor can be desensitized by phosphorylation Endocrine System - Endocrine and nervous system s are the two long-distance communication systems in the body - Hormones are delivered in the blood stream so actions have a slower onset but are longer lasting than neural signals Endocrine Glands – secrete hormones directly into ECF (in contrast to exocrine glands which secrete products to outside) - Derived from epithelial tissue - The endocrine system is not completely separate from the nervous system 1. Endocrine glands are often under nervous control (have neural inputs driving what is being released and what is not) 2. Some hormones are released from neurons (neurohormones) rather than endocrine glands (ie. Endocrine organs in the nervous system) 3. Many substances can act as hormones in the circulation or as neurotransmitters in the brain Hormones: - 3 classes: amines, protein and polypeptide hormones, steroid hormones 1. Amines (all possess amine groups) o Derived from amino acids tyrosine and tryptophan a. Catecholamines – derived from tyrosine 1. Dopamine – neurotransmitter and hypothalamic hormone 2. Norepinephrine and 3. Epinephrine – neurotransmitter and adrenomedullary hormones b. Other amines 1. Serotonin – neurotransmitter and hormone derived from tryptophan 2. Thyroid hormones (T4 = thyroxin, T3 = triodo-thyronine) – hormone derived from tyrosine 3. Histamine - derived from histidine o Catecholamine synthesis  They are derived from tyrosine  Successive enzymatic steps convert tyrosine to each catecholamine  The particular catcholamine secreted by an endocrine organ depends on the presence and activity of the appropriate enzymes 2. Protein and Polypeptide hormones o Growth hormone – hormone released by anterior pituitary o Atrial natriuretic peptide – hormone released by heart o Synthesized by proteolytic cleavage of a pre-prohormone in the ER o Resulting prohormones are then often cleaved to hormones during packaging of Golgi apparatus o o Hormones and pro-hormones are released by Ca2+ initiated exocytosis 3. Steroid hormones – produced by gonads, placenta (sex hormones) and adrenal cortex (mineralocorticoids, glucocorticoids and sex hormones) o Glucocorticoid – glucose metabolism and stress response o Mineralocorticoid – ion balance at the site of origin: adrenal cortex o All steroids are capable of crossing plasma membrane so they cannot be stored prior to release and instead diffuse out of cell into insterstitial fluid as soon as they are synthesized - The 3 hormone classes fall into 2 functional groups o Lipophobic messengers (hydrophilic): peptides, proteins, some amines (serotonin, catecholamines) o Lipophilic messengers (hydrophobic): steroids, some other amines (thyroid hormones) Property Lipophobic messenger Lipophilic messenger Chemical classes Amino acids, amines, peptides Steroids, thyroid hormones Storage in secretory cell Secretory vesicles None Mechanism of secretion Exocytosis Diffusion Transport in blood Dissolved Bound to carrier protein Location of receptor Plasma membrane (but endocytosis Cytosol or nucleus may occur) Signal transduction Open/ close ion channels Alter transcription of mechanism mRNA (alter protein Activate membrane bound enzymes synthesis) G proteins and 2 messenger systems Relative time to onset of Fast Slow response Relative duration of Short Long response Relative half life Short Long Metabolic breakdown (half- Rapid (< 1hr) Slow (hours – days) life) and secretion - Hydrophilic hormones are excreted by exocytosis, are transported in the blood and bind to cell surface receptors - Hydrophobic hormones diffuse through membranes (secretory and target cells) but require carrier proteins for transport in blood Effects on Target Cells: 1. Direct – activate or inhibit some function of the cell 2. Indirect – permissive effects – alter the sensitivity of the target cell to other hormones by up or down regulating their receptors Controls on Hormone Secretion: 1. Neural controls – direct control from CNS (hormones from hypothalamus: anterior pituitary, posterior pituitary) or via ANS (hormones from adrenal medulla, endocrine gland cell) 2. Another hormone (or self-inhibition) Eg. Hypothalamic releasing/ inhibiting hormones on anterior pituitary hormones 3. Changes in homeostatic regulated variable Eg. Blood glucose concentration on insulin and glucagon; concentration of Ca2+ on calcitonin and parathyroid hormone Endocrine Organs - Primary Endocrine Organs – primary function is the secretion of hormones - Secondary Endocrine Organs – secretion of hormones secondary to another main function Primary Endocrine Organs: - Pineal gland – historically described as the seat of the soul by Rene Descartes because he thought that emotions were transported by blood and though that the mind was found here. o Role: secreted melatonin (important for regulation of circadian rhythms) - Hypothalamus-pituitary complex – neuro- endocrine interface, master endocrine gland - Hypothalamus – is neural tissue with 2 main nuclei, has cell bodies and projects down to the pituitary gland. The axons from the hypothalamus terminate in the posterior pituitary where they release neurohormones into the blood - Posterior pituitary – composed of neural tissue. Also called neurohypophysis o Posterior pituitary hormones:  Octapeptides (peptides composed of 8 amino acids) synthesized in soma of giant neurons of the hypothalamus  Transported down axons and stored in synaptic vesicles in terminal knobs (similar to neurotransmitters) at blood vessels in posterior pituitary  Released when action potentials reach axon terminals 1. Antidiuretic Hormone (ADH) = vasopressin  Released from neurons from the paraventricular nucleus of the hypothalamus  Released in response to low blood volume, low blood pressure or high ECF osmotic pressure (detected by hypothalamic osmoreceptors)  Promotes water retention at kidney and raises blood pressure by vasoconstriction of systemic arterioles 2. Oxytocin – “hug hormone”  Released from neurons from the supra-optic nucleus of the hypothalamus  Regulates reproductive functions – uterine contractions, milk ejection - Anterior pituitary - composed of epithelial tissue. Also called adenohypophysis o Neurosecreteory cells in the hypothalamus release tropic hormones into hypothalamus pituitary portal system  Tropic hormones stimulate release of another hormone  Portal system – 2 or more capillary beds in a series o Tropic hormones stimulate the release of different hormones from the anterior pituitary o Hypothalamic-anterior pituitary hormones  There are at least 7 different hypothalamic tropic hormones  When released from neurons in the hypothalamus, they are at very high local concentrations (no dilution in general circulation)  At least 6 anterior pituitary hormones that are released to general circulation Hypothalamic-Anterior Pituitary Hormones - Hypothalamic tropic hormones – released like neurotransmitters by action potentials (integration from higher brain centres) 1. Prolactin Releasing Hormone (PRH) – stimulates prolactin release from anterior pituitary which stimulates mammary gland development and milk secretion in females 2. Prolactin Inhibiting Hormone (PIH) or dopamine – inhibits prolactin release from anterior pituitary 3. Thyrotropin Releasing Hormone (TRH) – stimulates TSH release fr
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