IMMS 1 Revision (part 1)Nick Richards & Byron Haywood-Alexander

Topics

1. Cells2. Homeostasis3. Molecular building blocks4. DNA/RNA5. Mitosis/Meiosis6. 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

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

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 wasteo maintain intracellular ionic balance

● Cell response to signals

● Molecules for intercellular adhesion

● Insulate - myelin sheath

?

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

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.

Exocytosis

1. Vesicles from the Golgi complex

2. Fuse with the plasma membrane

3. Expulsion of wasteORSecretion 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 receptor-

ligand 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 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

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

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

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+

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

?

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-

perfusiono headacheo confusiono 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.

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)

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

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

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

● 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

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 derivativeo 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

● Structureo Primary

o Secondary

o Quaternaryo Tertiary

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!

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 strandedo Topoisomeraseo DNA Helicase

● DNA polymerase

● Semi-conservative replication

Transcription

● Double stranded -> Single strandedo Topoisomeraseo DNA Helicase

● RNA polymerase

● Messenger RNA (mRNA)

ANTI-SENSE DNA

Translation● mRNA -> Ribosome

● tRNA○ Anticodon

● Splicingo Intronso Exons

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