imms 1 revision (part 1) nick richards & byron haywood-alexander
TRANSCRIPT
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IMMS 1 Revision (part 1)Nick Richards & Byron Haywood-Alexander
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Topics
1. Cells2. Homeostasis3. Molecular building blocks4. DNA/RNA5. Mitosis/Meiosis6. Genetic disease
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1. Cells
Functional unit of the body, compartmentalised by a cell membrane, containing intracellular organelles and cytoplasm. Many cellular metabolic processes occur here including those that allow molecules into and out of the cell.
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Require an electron microscope
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OrganellesNucleus - cell ‘brain’, double nuclear membrane, DNA, nucleolus produce rRNA
Mitochondria - cell ‘battery’, oxidative phosphorylation, mtDNA, double membrane (inner highly folded)
● Outer membrane - lipid synthesis and fatty acid metabolism
● Inner membrane* - Respiratory (electron transport) chain ATP production
● Matrix - Tricarboxylic acid (Krebs’) cycle
● Intramembranous space - nucleotide phosphorylation
Endoplasmic reticulum - flat folded sheets of membrane, nuclear pores
● Rough - protein production
● Smooth - membrane lipid production, protein processing
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Organelles
Golgi apparatus - parallel membrane sheets - process and modify ER products● Cis (nuclear) face - receive smooth ER vesicles, protein phosphorylation● Medial Golgi - modify products by adding sugars ● Trans Golgi Network - proteolysis of peptides into active forms, sorting of
molecules into vesicles
Vesicles - spherical membrane bound organelles to transport and store material
● Cell surface derived: pinocytotic and phagocytic vesicles
● Golgi-derived transport vesicles
● ER-derived transport vesicles
● Lysosomes
● Peroxisomes
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Organelles
Lysosomes (waste disposal system) - contain many acid hydrolases. H+ATPase on membrane creates optical pH 5 environment for enzymes.
Peroxisomes - contain enzymes that break down long-chain fatty acids D-amino acid oxidase, Catalase, Urate oxidase
Cytoskeleton - filament proteins supporting structure of the cell
● Microfilaments - Actin forms a mesh (cell cortex) to inner cell membrane
● Intermediate filaments - differ from cell to cell - spread tensile forces
● Microtubules - Tubulin arise from centromere (2 centrioles) - not RBC
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Cell membranes● Phospholipid bilayer● Contain glycolipids, glycoproteins, cholesterol and embedded proteins.
Proteins: Transmembrane (integral), Catalytic, Structural (pumps, gates, receptors, adhesion molecules, energy transducers).
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Cell membrane function● Barrier the external environment and compartmentalise the cell
● Semi-permeable:o absorb nutrients and expel wasteo maintain intracellular ionic balance
● Cell response to signals
● Molecules for intercellular adhesion
● Insulate - myelin sheath
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Cell JunctionsOccluding junctions - prevent molecule leakage
● Tight junctions
Anchoring junctions● Actin filament sites
o cell-cell junction (adherens junctions)o cell-matrix junctions (focal adhesions)
● Intermediate filament siteso cell-cell junction (desmosomes)o cell-matrix junction (hemidesmosome)
Communicating● Gap junctions● Chemical synapses
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EndocytosisEnergetic process to absorb/engulf molecules into cell.
Phagocytosis* (eating) - macromolecules/ entire cell to form phagosomes
Pinocytosis (drinking) - dissolved solutes
Receptor mediated* - specific, depressed areas: coated pits.
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Exocytosis
1. Vesicles from the Golgi complex
2. Fuse with the plasma membrane
3. Expulsion of wasteORSecretion of enzymes/hormones
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Movement across membranes
Movement types● Passive diffusion● Facilitated diffusion through protein channels with(out) carrier proteins● Active transport
Examples
● Gaseous exchange along chemical gradient
● Glucose - protein assisted which is upregulated by insulin. Voltage gated channels activated by action potentials.
● NaK ATPase pump - going against chemical and electrical gradients
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Receptors
Gateway to intracellular signals
● open a channel● activate an intracellular enzyme● induce second messenger● migrate to nucleus as receptor-
ligand complex
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2.Homeostasis
Control of the internal environment
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Communication
Types● Endocrine - hormones● Nervous - currents and neurotransmitters● Immune - antibodies, cytokines, interleukins
Receptor and ligand required
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Cell to cell signaling
Immunity - T lymphocytes secreting IL2, cytokines
Neuro synapses, neuromuscular junction, clotting
Endocrine system - hypothalamus, pituitary, thyroid, parathyroid, thymus, pancreas, kidney, gonads, adrenals
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Types of hormonePeptide - insulin, growth hormone, TSH● From short chain of AA to small proteins● Some glycoproteins● Hydrophilic - receptors
Steroid - testosterone, oestrogen, cortisol
● Synthesised from cholesterol
● Different enzymes produce hormones
● Lipid soluble - cross membranes but require transport proteins
Amino-acid derivative - adrenaline, T4, T3
● synthesised from tyrosine
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Feedback
Positive feedback - amplification of signal
Negative feedback loop - centre of homeostasis
● Clotting cascade
● Oxytocin during childbirth
● Blood sugar regulation
● Temperature regulation
● Blood pressure regulation
● Metabolism/thyroid regulation
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Water Distribution
Total body water ~ 42L 60% of body weight
40% of body weight intracellular fluid - 28L
Plasma - 3L
20% of body weight extracellular fluid - 14L
Interstitial - 10L
K+ HCO3-
Na+
Cl-
Transcellular - 1L-CSF-Digestive juices-Mucus
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Water Homeostasis● Fluid compartments are in osmotic equilibrium
● Solutes (osmotically active) in ICF and ECF create osmotic gradients
● Any change in solutes in any compartment results in a water movement
ECF ICF
K+Urea
Glucose
Na+
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Water loss:
● Kidneys
● Insensible losseso sweato breatho vomitingo faeces
Water Homeostasis
Water intake:● Drink - thirst, social● Diet● IV fluid
Regulatory hormones● Antidiuretic hormone● Aldosterone● Atrial natriuretic peptide
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Definitions
Osmosis - net movement of solvent molecules through a semipermeable membrane to a higher solute concentration.
Osmolality - measure of the number of dissolved particles per kg of fluid.Osmolarity - measure of the number of dissolved particles per L of fluid.
Osmotic pressure - pressure applied to a solution, by a pure solvent, required to prevent inward osmosis. Through a semipermeable membrane.
Oncotic pressure - form of osmotic pressure exerted by proteins that tends to pull fluid into its solution.
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Water homeostasis mechanisms
Water loss from ECF● ↑ solute or ↓ fluid results in an ↑ osmolality● Detected by osmoreceptors in hypothalamus● Release of antidiuretic hormone (ADH) from posterior pituitary● ADH acts by increasing water reabsorption in the kidneys● Dilutes solute and returns ECF water to normal
Decreased renal blood flow● ↓ water in ECF results in ↓ circulating volume results in ↓ renal blood flow● Kidney release of Renin and activation of RAAS● Angiotensin II and aldosterone increase Na+ reabsorption (exchange K+
and H+) bringing water. Also stimulates ADH.
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Dehydration
● Low intake
● Excess loss
● Low ADH
● Water deprivation● Vomiting● Diarrhoea● Burns● Heavy Sweating● Diabetes insipidus● Diabetes mellitus● Drugs
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Water excess
● High intake
● Decreased loss
● Excess ADH
● Hyponatraemia● Cerebral over-
perfusiono headacheo confusiono convulsions
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Oedema
Oedema - excess water in the intercellular tissue space.● inflammatory (leakage)● Venous (increased end pressure)● Lymphatic (blocked)● Hypoalbuminaemic
Serous effusion - excess water in a body cavity.
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SodiumHypernatraemia● Water deficit
o low intakeo osmotic diuresiso DI
● Sodium excesso mineralocorticoid excess
S+S: cerebral intracellular dehydration (confusion, tremors, irritability), hypertension, oedema/serous effusion
Hyponatraemia
● Artefactual
● Sodium loss
o Diuresis
o Addison’s disease
● Excess water
o IV fluids
o SIADH
● Excess water & sodium
o Oedema (CCF, liver disease)
S+S: intracellular overhydration (headache, confusion, convulsions)
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Potassium
Excretion from intestines and kidneys (Na/K ATPase pump controlled by aldosterone)
Hyperkalaemia● Decreased K+ loss
o renal failureo diuretic/ACE-inhibitorso Addison’s
● Redistributiono acidosis
S+S: risk of cardiac arrest
Hypokalaemia
● Potassium loss
o D+V
o Diuretics
o Hypomagnesaemia
o Conn’s and Cushing’s
● Redistribution
o Alkalosis
o Refeeding syndrome
S+S: Weakness, dysrhythmia
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CalciumHypercalcaemia● Hyperparathyroidism● Malignancy
o Skeletal metso PTH-like hormone from
tumours● Vitamin D toxicity● Granulomatous disease (TB)
S+S: Metastatic calcificationBones, stone, psychic groans, abdominal moans, thrones.
Hypocalcaemia
● Vit D deficiency
● Mg deficiency
● Renal disease
● Parathyroidectomy
● Intestinal malabsorption
S+S: tetany, carpopedal spasm
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3. Molecular building blocks
Simple molecules form complex, large macromolecules with functions:
● Structure● Osmotic● Enzyme
● Other specific
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Carbohydrates/Saccharide/Sugars
● Cn(H2O)n Mono, Di, Oligo, Poly
● Groupso Hydroxylo Aldehydeo Ketoneo Carboxyl
● OH group react with OH/NH = O/N-glycosidic bond
● Polysaccharides: 1-4 and 1-6 bonding forming Glycogen, Starch
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Lipids/Fatty acids● Straight hydrocarbon chain with carboxyl group
● Eicosanoids - major biological function
o derived from eicosanoic acid
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Nucleotides● Sugar + nuclear base + single phosphate group
o Purine derivativeo Pyrimidine derivative
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Aminoacids● Charge determined by all 3
groups
● Change at different pH
● Side chain determine polarity and non-polarity
● Strong peptide bond CO-NH. Requires proteolytic enzymes.
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Chiral centres
Most sugars in the human body are D form, whereas protein take L-form!
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Proteins● Long AA chains
● Varied function - structure dependent
● Structureo Primary
o Secondary
o Quaternaryo Tertiary
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Enzymes● Biological catalyst - bind but to not get
used up
● Speed-up and regulate reaction rate
● Optimum temperature and pH
● Activation, modification, inhibition
● Isoenzymes - different structure, catalyse same reaction
Disease marker!
Drug target!
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Co-enzymes● Organic structures (nonprotein) that help maximise
organic enzyme active site
● Cannot catalyse alone
● Metal ions (Fe2+, Mg2+, Zn2+), vitamin derivatives (thiamine pyrophosphate)
● Activation-transfer coenzymes
● Oxidation-reduction coenzymes
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Forces● Van der Waals - weak attractive/repulsive force between all atoms due to
fluctuating electrical charge.
● Hydrogen bonds - interaction between polar groups. Important in AA side chains, O/N in main chain and water.
● Hydrophobic forces - as uncharged and non-polar side chain repel water, they tend toward a protein core.
● Ionic bonds - between fully/partially charged groups
● Disulphide bonds - very strong covalent bonding between sulphur atoms.
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DNA/RNA● Base Nucleotides
● Complementary Base Pairing
● DNA Polymerase
● Sense and Anti-Sense Strands
● RNA
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Maternal Chromosome
Paternal Chromosome
Gene locus
Alleles
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Replication of DNA
● Double stranded -> Single strandedo Topoisomeraseo DNA Helicase
● DNA polymerase
● Semi-conservative replication
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Transcription
● Double stranded -> Single strandedo Topoisomeraseo DNA Helicase
● RNA polymerase
● Messenger RNA (mRNA)
ANTI-SENSE DNA
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Translation● mRNA -> Ribosome
● tRNA○ Anticodon
● Splicingo Intronso Exons
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Mis-Sense and Non-Sense● Mis-Sense
o Single nucleotide polymorphism (SNP)o Different amino-acido Examples?
Sickle Cell (CAG -> CTG)
● Non-Senseo Single nucleotide polymorphism (SNP)o Premature stop codono Examples?
Duchenne’s Muscular DystrophyGOWER’S SIGN
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