Download IMMS 1 Revision

IMMS 1 Revision (part 1)
Nick Richards & Byron Haywood-Alexander
Topics
1. Cells
2. Homeostasis
3. Molecular building blocks
4. DNA/RNA
5. Mitosis/Meiosis
6. Genetic disease
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.
Require an electron microscope
Organelles
Nucleus - 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
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
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
Cell membranes
● Phospholipid bilayer
● Contain glycolipids, glycoproteins, cholesterol and embedded proteins.
Proteins: Transmembrane (integral), Catalytic, Structural (pumps, gates,
receptors, adhesion molecules, energy transducers).
Cell membrane function ?
● Barrier the external environment and compartmentalise the cell
● Semi-permeable:
o absorb nutrients and expel waste
o maintain intracellular ionic balance
● Cell response to signals
● Molecules for intercellular adhesion
● Insulate - myelin sheath
Cell Junctions
Occluding 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 sites
o cell-cell junction (desmosomes)
o cell-matrix junction (hemidesmosome)
Communicating
● Gap junctions
● Chemical synapses
Endocytosis
Energetic 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.
Exocytosis
1. Vesicles from the Golgi complex
1. Fuse with the plasma membrane
1. Expulsion of waste
OR
Secretion of enzymes/hormones
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
Receptors
Gateway to intracellular signals
●
●
●
●
open a channel
activate an intracellular enzyme
induce second messenger
migrate to nucleus as receptorligand complex
2.Homeostasis?
Control of the internal environment
Communication
Types
● Endocrine - hormones
● Nervous - currents and neurotransmitters
● Immune - antibodies, cytokines, interleukins
Receptor and ligand required
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
Types of hormone
Peptide - 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
Feedback
Positive feedback - amplification of signal
● Clotting cascade
● Oxytocin during childbirth
Negative feedback loop - centre of
homeostasis
● Blood sugar regulation
● Temperature regulation
● Blood pressure regulation
● Metabolism/thyroid regulation
Water Distribution
Total body water ~ 42L 60% of body weight
Cl-
K+
HCO3-
40% of body weight
intracellular fluid - 28L
Interstitial - 10L
20% of body weight
extracellular fluid - 14L
Plasma - 3L
Na+
Transcellular 1L
-CSF
-Digestive juices
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
Urea Na+
Glucose
ICF
K+
Water Homeostasis
Water intake:
● Drink - thirst, social
● Diet
● IV fluid
Water loss:
● Kidneys
● Insensible losses
o sweat
o breath
o vomiting
o faeces
?
Regulatory hormones
● Antidiuretic hormone
● Aldosterone
● Atrial natriuretic peptide
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.
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.
Dehydration
● Low intake
● Excess loss
● Low ADH
●
●
●
●
●
●
●
●
Water deprivation
Vomiting
Diarrhoea
Burns
Heavy Sweating
Diabetes insipidus
Diabetes mellitus
Drugs
Water excess
● High intake
● Decreased loss
● Excess ADH
●
●
Hyponatraemia
Cerebral over-perfusion
o
headache
o
confusion
o
convulsions
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.
Sodium
Hypernatraemia
● Water deficit
o low intake
o osmotic diuresis
o DI
● Sodium excess
o 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
Potassium
Hyperkalaemia
● Decreased K+ loss
o renal failure
o diuretic/ACE-inhibitors
o Addison’s
● Redistribution
o 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
Excretion from intestines and kidneys (Na/KS+S:
ATPase
pump controlled
by
Weakness,
dysrhythmia
aldosterone)
Calcium
Hypercalcaemia
● Hyperparathyroidism
● Malignancy
o Skeletal mets
o PTH-like hormone from
tumours
● Vitamin D toxicity
● Granulomatous disease (TB)
Hypocalcaemia
S+S: Metastatic calcification
Bones, stone, psychic groans,
abdominal moans, thrones.
S+S: tetany, carpopedal spasm
● Vit D deficiency
● Mg deficiency
● Renal disease
● Parathyroidectomy
● Intestinal malabsorption
3. Molecular building blocks
Simple molecules form complex, large
macromolecules with functions:
● Structure
● Osmotic
● Enzyme
● Other specific
Carbohydrates/Saccharide/Sugars
● Cn(H2O)n Mono, Di, Oligo, Poly
● Groups
o Hydroxyl
o Aldehyde
o Ketone
o Carboxyl
● OH group react with OH/NH = O/N-glycosidic bond
● Polysaccharides: 1-4 and 1-6 bonding forming Glycogen, Starch
Lipids/Fatty acids
● Straight hydrocarbon chain with carboxyl group
● Eicosanoids - major biological function
o derived from eicosanoic acid
Nucleotides
● Sugar + nuclear base + single phosphate group
o Purine derivative
o Pyrimidine derivative
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.
Chiral centres
Most sugars in the human body are D form, whereas protein take L-form!
Proteins
● Long AA chains
● Varied function - structure
dependent
● Structure
o Primary
o Secondary
o Tertiary
o Quaternary
Enzymes
● Biological catalyst - bind but to not get
used up
● Speed-up and regulate reaction rate
● Optimum temperature and pH
● Activation, modification, inhibition
Disease marker!
● Isoenzymes - different structure,
catalyse same reaction
Drug target!
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
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.
DNA/RNA
● Base Nucleotides
● Complementary Base Pairing
● DNA Polymerase
● Sense and Anti-Sense Strands
● RNA
Maternal
Chromosome
Paternal
Chromosome
Gene locus
Alleles
Replication of DNA
● Double stranded -> Single
stranded
o Topoisomerase
o DNA Helicase
● DNA polymerase
● Semi-conservative
replication
Transcription
ANTI-SENSE DNA
● Double stranded ->
Single stranded
o Topoisomerase
o DNA Helicase
● RNA polymerase
● Messenger RNA
(mRNA)
Translation
● mRNA -> Ribosome
● Splicing
o Introns
o Exons
● tRNA
○ Anticodon
Mis-Sense and Non-Sense
● Mis-Sense
o Single nucleotide polymorphism (SNP)
o Different amino-acid
o Examples?
 Sickle Cell (CAG -> CTG)
● Non-Sense
o Single nucleotide polymorphism (SNP)
o Premature stop codon
o Examples?
 Duchenne’s Muscular Dystrophy
GOWER’S SIGN