Biochemical Basis of Therapeutics Flashcards

Question

What type of receptors do the preganglionic neurotransmitters act on in the Parasympathetic NS?

Answer 1

Nicotinic cholinergic receptors (ligand-gated ion channels)

Answer 2

Adrenergic receptors (αlpha/beta) G protein-coupled receptors (GPCRs)

Answer 3

Muscarinic cholinergic receptors (M1-M5) G protein-coupled receptors (GPCRs)

Answer 4

Acetylcholine (Ach)

Answer 5

Nicotinic cholinergic receptors (ligand-gated ion channels)

Answer 6

Drugs will need to penetrate the BBB which is highly selective Effects are likeley to be widespread

Answer 7

Non-selective / non-specific effects Widespread effects - side effects

Answer 8

Allows for specific targeting of function Minimal off-target effects

Answer 9

2 alpha subunits

Answer 10

ligand-gated non-selective cation channel

Answer 11

Pupil dilation Vasoconstriction Decreased salivation Increased heart rate Increased force of heart contraction Bronchodilation Reduced motility in GI system Increased metabolism in liver (gluconeogenesis) Bladder relaxation Ejaculation

Answer 12

Neurotransmitter synthesis (e.g. α-methyl-tyrosine) Neurotransmitter storage (e.g. reserpine, amphetamine) Autoreceptors (e.g. clonidine) Termination of signalling (e.g. moclobemide) Post synaptic receptors * Adrenergic receptor antagonists - e.g. doxazosin, propranolol, atenolol * Adrenergic receptor agonists - e.g. salbutamol

Answer 13

Monoamine neurotransmitters (NA, Dopamine, Serotonin) are metabolised by monoamine oxidase (MAO). So to protect them, they are taken into vesicles via the vesicular monoamine transporter (VMAT). Reserpine is a drug that blocks the VMAT, preventing NA uptake into vesicles leading to its metabolisation by MAO. This decreases the nerve of NA.

Answer 14

Monoamine neurotransmitters (NA, Dopamine, Serotonin) are metabolised by monoamine oxidase (MAO). So to protect them, they are taken into vesicles via the vesicular monoamine transporter (VMAT). Drugs such as Amphetamine, Tyramine and Ephedrine enter via the ‘uptake 1’ channel and compete with NA to enter the vesicles via VMAT displacing NA from storage causing leakage into the synaptic gap + increasing the concentration of free NA for release into the synaptic gap.

Answer 15

Autoreceptors inhibit neurotransmitter release via exocytosis in order to regulate neurotransmission Clonidine stimulates these autoreceptors (α2AR) which inhibits neurotransmitter release.

Answer 16

Signalling is terminated by the uptake of neurotransmitters followed by break down by Monoamine Oxidase (MAO) (and catechol-0-methyltransferase (COMT) for dopamine) into inactive metabolites MAO inhibitors (e.g. Moclobemide) can be utilised to prevent signal termination and increase/maintain neurotransmitter levels

Answer 17

Wine and dairy products such as cheese and yoghurt contain tyrosine. Tyrosine is broken down by MAO, so MAO inhibitors prevents breakdown of tyrosine and leads to an accumulation and hypertensive crisis's as a result

Answer 18

Targeting upstream processes like neurotransmitter synthesis or degradation can have widespread effects, whilst postsynaptic receptor modulation tends to be more localised, reducing unintended systemic effects Specificity of action

Answer 19

Pupil constriction Tears Decreased heart rate Vasoconstriction Increased GI motility Bladder contraction Erection

Answer 20

Neurotransmitter synthesis (e.g. hemicholinium) Neurotransmitter storage (e.g. inhibitors of VAChT) Neurotransmitter release (e.g. Botulinum toxin - i.e. botox) Termination of signalling (acetylcholinesterase (AChE) inhibitors - e.g. Neostigmine, Edrophonium) Ganglia receptors (e.g. hexamethonium) Postsynaptic (muscarinic) receptors * Muscarinic receptor antagonists (anti-cholinergics) - e.g. atropine, darifenacin * Muscarinic receptor agonists

Answer 21

Increased/high BP distends arterial wall Afferent nerve endings are stimulated by resultant stretch Sends signal to the brain (NTS) , which compares the BP signal to a set point. Brain coordinates: * Increased parasympathetic drive/innervation to heart * This leads to a decreased heart rate and decreased cardiac output (CO) + * Decreased sympathetic drive/innervation to heart, arteries, veins * This leads to a decreased heart rate and decreased force of contraction → therefore decreased cardiac output (CO) * This leads to decreased arterial constriction and venous constriction This causes BP to fall to the set point If BP falls, opposite effects occur to bring it back up to the set point

Answer 22

Gs s = stimulate Gi i = inhibit Gq

Answer 23

NA Receptors – β1, β2, β3 Dopamine Receptors – D1, D5 5-HT Receptors – 5-HT4, 5-HT6, 5-HT7 Histamine Receptors – H2 V2

Answer 24

1. Binding of agonist to receptor causes conformational change 2. GDP exchanged for GTP bound to G Protein 3. Hydrolysis of GTP provides energy for dissociation of α-subunit, from β/ɣ subunits 4. α-subunit activates Adenylyl Cyclase which results in the formation of cAMP 5. cAMP activates Protein Kinase A which phosphorylates downstream target proteins Summary: ↑ Adenylyl cyclase → ↑ cAMP → activates PKA

Answer 25

Ach Receptors – M2, M4 NA Receptors – α2 Dopamine Receptors – D2, D3, D4 5-HT Receptors – 5-HT1, 5-HT5 GABA Receptors – GABAb

Answer 26

1. Binding of agonist to receptor causes conformational change 2. GDP exchanged for GTP bound to G Protein 3. Hydrolysis of GTP provides energy for dissociation of α-subunit, from β/ɣ subunits 4. α-subunit inhibits Adenylyl Cyclase which prevents the formation of cAMP 5. Therefore decreased Protein Kinase A activity and decreased phosphorylation of downstream target proteins 6. Also activation of potassium channels + inhibition of calcium channels Summary: ↓ cAMP → ↓ PKA, opens K⁺ channels, closes Ca²⁺ channels

Answer 27

Ach Receptors – M1, M3, M5 NA Receptors – α1 5-HT Receptors – 5-HT2 H1 V1

Answer 28

1. Binding of agonist to receptor causes conformational change 2. GDP exchanged for GTP bound to G Protein 3. Hydrolysis of GTP provides energy for dissociation of α- subunit, from β/ɣ subunits 4. α-subunit activates PLC which results in the formation of IP3 and DAG from PIP2. 5. IP3 mobilises Ca2+ from intracellular stores and DAG stimulates PKC ↑ intracellular Ca2+ activates Ca2+ dependent response including muscle contraction PKC phosphorylates downstream target proteins – e.g. muscle contraction Summary: ↑ PLC → ↑ IP3 + DAG → ↑ Ca²⁺ + activates PKC

Answer 29

Cell Body (Soma) Dendrites Axon Myelin Sheath Nodes of Ranvier Axon Terminals Synapse

Answer 30

Contains the nucleus and organelles essential for cellular function and metabolism Integrates the information received by the dendrites

Answer 31

Branch-like structures that receive signals from other neurons and convey them to the cell body

Answer 32

A long projection that transmits electrical impulses (action potentials) away from the cell body toward other neurons or muscles May or may not be insulated by myelin The axon hillock is where the action potential is initiated

Answer 33

A fatty layer (formed by oligodendrocytes in the CNS and Schwann cells in the PNS) that insulates the axon and speeds up signal transmission

Answer 34

Gaps between segments of the myelin sheath where ion exchange occurs, allowing for rapid signal conduction (saltatory conduction)

Answer 35

Endings of the axon that release neurotransmitters into the synaptic cleft to communicate with target cells

Answer 36

Approximately -55 to -70mv During this state there are: * More sodium ions (Na⁺) outside than inside the neurone * More potassium ions (K⁺) inside than outside the neurone

Answer 37

The neuron cell membrane is super permeable to potassium ions, and so lots of potassium leaks out of the neuron through potassium leakage channels The neuron cell membrane is partially permeable to sodium ions, so sodium atoms slowly leak into the neuron through sodium leakage channels The cell wants to maintain a negative resting membrane potential, so pumps potassium back into the cell and pumps sodium out of the cell at the same time Sumary: * Sodium-potassium pump actively transports 3 Na⁺ ions out and 2 K⁺ ions into the neuron * The membrane is more permeable to K⁺ than Na⁺, allowing K⁺ to leak out

Answer 38

Resting → Depolarisation → Repolarisation → Hyperpolarisation → Resting

Answer 39

1. The neuron is at rest, maintaining a stable negative charge inside (~ -70mV) 2. A stimulus causes the release of neurotransmitters which bind to receptors on the dendrites **EPSPs** 3. This causes the opening of voltage-gated Na⁺ channels so that there is an influx of Na⁺ into the neurone. As a result the cell depolarises and produces an Excitatory Post-Synaptic Potential (EPSP) **Rapid depolarisation** 4. These EPSPs sum up and when the AP threshold (-55 mV) is reached more voltage-gated Na⁺ channels open, causing a large influx of Na⁺ into the neurone to become highly positive (~ +30mV) **Repolarisation** 5. Voltage-gated Na⁺ channels close, stopping Na⁺ entry and voltage-gated K⁺ channels open, allowing K⁺ to leave the neuron. This means the cell loses positively charged ions so the membrane potential becomes more negative, returning back toward resting state **Hyperpolarisation** 6. As the action potential passes through, the K⁺ channels remain open causing the membrane potential to drop below resting potential (~ -80mV). This makes the neuron temporarily less likely to fire another action potential. 7. The K⁺ channels close and the Na⁺/K⁺ pump restores the original ion balance to reestablish the resting state.

Answer 40

Chemical (the most common form) Electrical

Answer 41

Influx of Ca²⁺ via voltage-gated channels

Answer 42

EPSP = depolarisation, increases likelihood of action potential being fired IPSP = hyperpolarisation, decreases likelihood of action potential being fired

Answer 43

1. A nerve impulse/action potential arrives at the presynaptic terminal, causing depolarisation 2. This depolarisation of the membrane causes voltage-gated Ca²⁺ channels to open, allowing Ca²⁺ influx into the presynaptic terminal 3. The increased Ca²⁺ concentration triggers synaptic vesicles to fuse with the presynaptic membrane and release neurotransmitters into the synaptic cleft via exocytosis 4. The released neurotransmitters diffuse across the synaptic cleft and bind to specific receptors on the postsynaptic neuron

Answer 44

Ionotropic Metabotropic

Answer 45

Ligand-gated ion channels that mediate fast responses Agonist activation induces a conformational change, opening the ion pore

Answer 46

Nicotinic ACh receptors (non selective cation channel) NMDA Glutamate receptors (non selective cation channel) AMPA Glutamate receptors (non selective cation channel) 5HT3 receptors (non selective cation channel) GABAa receptors (selective chloride channel)

Answer 47

GPCRs that initiate slower, longer-lasting effects via secondary messengers Gives more selectivity of function over ionotropic receptors which are selective only to their ion Different metabotropic receptors can couple to different G proteins → different receptors can stimulate different signalling cascades → different functional outcomes

Answer 48

Muscarinic ACh receptors All 5HT receptors except for 5HT3 GABAb receptors Dopamine receptors

Answer 49

Simple diffusion away from the synapse Reuptake Enzymatic degradation

Answer 50

Acetylcholinesterase (AChE)

Answer 51

NET transporter

Answer 52

Displace NA from vesicles → increases release + inhibit MAO

Answer 53

Noradrenaline

Answer 54

Acetylcholine

Answer 55

Autoreceptor-mediated negative feedback

Answer 56

The period immediately after an action potential during which no new action potential can be initiated, regardless of stimulus strength, because voltage-gated Na⁺ channels are inactivated

Answer 57

The period following the absolute refractory period during which a very strong stimulus is required to initiate an action potential, as some Na⁺ channels are reset, but K⁺ efflux is still occurring, making the membrane more negative than resting

Answer 58

DNA sequence with the most common nucleotide in each position Derived from the Human Genome Project No one has the consensus sequence Comparisons are always made against the consensus sequence

Answer 59

Approximately 25,000 genes

Answer 60

Different versions of a gene that arise due to mutations in the DNA sequence

Answer 61

The normal, non-mutated form of a gene as it commonly occurs in a natural population

Answer 62

A type of mutation where one nucleotide is changed

Answer 63

Genetic mutation Ionising radiation emitted from the sun Radon leaks from the ground Background radiation

Answer 64

Synonymous Non-synonymous Frame shift

Answer 65

A mutation that does not change the amino acid and typically does not affect protein function Normally occur in the the third base of a triple codon

Answer 66

A mutation that changes the amino acid sequence. Typically occur at the first and second base of a triple codon Can result in no functional amino acid change (E.g. Glu to Asp mutation - no/very little change in protein function) Can result in small changes in protein function (Eg. Arg114Cys in Cytochrome P450 2C9) Can result in a major change in protein function (Eg. Glu6Val in haemaglobin S)

Answer 67

A mutation from insertion/deletion that shifts the reading frame and usually inactivates the protein.

Answer 68

Copying of the same allele multiple times, potentially leading to too much protein (e.g. CYP2D6 UM)

Answer 69

The complete loss of a gene, resulting in no protein production (e.g. CYP2D6*5)

Answer 70

Loss of a portion of a gene, producing a shortened, inactive protein

Answer 71

The genetic makeup of an organism Refers to the specific DNA sequence or alleles an individual carries (e.g. AA, Aa, aa) Inherited from parents

Answer 72

The observable traits or characteristics of an organism, resulting from genotype and environmental interaction

Answer 73

Two normal alleles → normal protein function

Answer 74

One normal and one mutated allele → reduced or partial function E.g. individuals with heterozygous genotype CYP2C9 *1/*3 may have an intermediate ability to metabolise drugs, leading to a moderate risk of drug toxicity or ineffective drug response (IM)

Answer 75

Two mutated alleles → significantly altered or lost protein function E.g. * Individuals with mutated genotype CYP2C9 *3/*3 may have a reduced ability to metabolise certain drugs, leading to toxicity (PM) * If the mutation results in an overactive protein, drug metabolism may be faster, which could lead to suboptimal drug effects (UM)

Answer 76

A group of genes or DNA variations (like SNPs) that are inherited together from a single parent Usually found on the same chromosome segment

Answer 77

People of African descent have a higher prevalence of the CYP2D6*17 allele, which is associated with increased metabolism of some drugs (UM) East Asian populations have a higher frequency of the CYP2C19*2 allele, which may lead to slower drug metabolism (PM)

Answer 78

Due to evolution, genetic drift, founder effects and limited gene flow across populations

Answer 79

Mutations in genes that influence enzymes responsible for drug metabolism (e.g. CYP450 family) determine how quickly or slowly a drug is broken down in the body Too little activity causes too high a plasma concentration and gives rise to toxicity or result in lack of activity for prodrugs (E.g. codeine and cytochrome P450 2D6*5) Too much activity can cause treatment failure or cause toxicity if it a prodrug (E.g. codeine & cytochrome P450 2D6*2 UM)

Answer 80

Mutations in genes can alter drug targets such as receptors, enzymes, or transporters, which will influence the drug's effects/efficacy: * Drug may not bind sufficiently to elicit response (agonist) * Drug may not bind sufficiently to inhibit response (antagonist) Mutations in uptake transporters can influence drug concentration in the body Mutations can cause some receptors to not work at optimal level

Answer 81

Mutations can affect: * Metabolism * Uptake * Binding * Reuptake Metabolism (e.g. mutations in CYP450s) : * Ultra-rapid Metabolisers (UMs) = break down drugs too fast → low drug levels → reduced efficacy * Extensive Metabolisers (EMs) = normal drug metabolism, ideal drug levels * Intermediate Metabolisers (IMs) = slower drug metabolism → potential for drug accumulation and toxicity * Poor Metabolisers (PMs) = very slow metabolism → high drug levels → increased toxicity risk Mutations in transporters (e.g. p glycoprotein) could lead to accumulation of drug due to reduced efflux function Efficacy of drug is determined by genotype of receptors present (e.g. drug may not bind sufficiently)

Answer 82

Ultra-rapid Metabolisers (UMs) = break down drugs too fast → low drug levels → reduced efficacy Extensive Metabolisers (EMs) = normal drug metabolism, ideal drug levels Intermediate Metabolisers (IMs) = slower drug metabolism → potential for drug accumulation and toxicity Poor Metabolisers (PMs) = very slow metabolism → high drug levels → increased toxicity risk

Answer 83

Genetic screening is expensive, requires specialist equipment + expertise and is not practical in a clinical environments so using ethnic patterns can help predict likely genotypes

Answer 84

Alternative drugs Add on drugs Adjust dosing Therapeutic drug monitoring (TDM)

Answer 85

Towards the front of the body

Answer 86

Towards the back of the body

Answer 87

Towards the top of the body

Answer 88

Towards the bottom of the body

Answer 89

Towards the midline of the body

Answer 90

In the midline rather than towards the midline

Answer 91

Away from the midline

Answer 92

Towards the centre of the body

Answer 93

Away from the centre of the body

Answer 94

Towards the surface of the body

Answer 95

Away from the surface of the body

Answer 96

Hair Skin Nails Sweat + oil glands

Answer 97

Protects deeper tissues from damage Regulation of body temperature Sensation – touch, pain, pressure, temperature Excretion of urea and uric acid (via sweat) Synthesis of Vitamin D (from cholesterol in the presence of sunlight) Assist in manipulation and grasping of small objects Scratching

Answer 98

Mechanical – physical barrier Chemical – impermeable keratinized cells Bacterial – unbroken surface, antibacterial secretions UV – melanin pigment Thermal – heat, cold & pain receptors Dessication – waterproof keratinized cells

Answer 99

Structure and movement of the body Attachment points for muscle Protects internal organs Produces blood cells Stores minerals

Answer 100

Long bone – act as levers Flat bone – protect delicate organs Short bones – confers strength and flexibility Irregular bone – anchorage points

Answer 101

Areas where bones meet Allow movement Lubricated by synovial fluid

Answer 102

Skeletal muscle * Moves the skeleton * Production of body heat * Facial muscles – expression, speech, mastication * Thorax and diaphragm – respiration * Abdomen – protect internal organs, contract to assist blood flow, defecation, vomiting and child birth Cardiac muscle * Found in the heart * Pumps blood throughout the body Smooth muscle * Found in walls of internal organs (e.g. stomach, intestines, blood vessels) * Helps move substances through the body (digestion, blood flow)

Answer 103

Class I lever: * Fulcrum (i.e. the pivot point) in the middle - like a seesaw * Weight balanced over fulcrum, therefore only a small amount of force needed * Limited in how much weight and how high can be lifted * E.g. neck joint Class II lever: * Weight is located between fulcrum and force * Can lift a considerable amount of weight * Limited in height * E.g. standing on tiptoes Class III lever: * Most common type of lever * The force is located between the weight and the fulcrum * Does not allow a great weight to be lifted * Can be lifted a great distance * Weight can be increase * E.g. bicep curl

Answer 104

Nose + nasal cavity + sinuses: * filters, warms and moistens incoming air * produce mucus * act as resonators for sound * lighten skull Pharynx (throat) - passageway for air and food Larynx (voice box) - produces sound + routes air into trachea Trachea (windpipe): * carries air to bronchi * lined with cilia and mucus to trap dust Bronchi + bronchioles - direct air to alveoli Alveoli - air sacks where gas exchange occurs (O₂ enters blood, CO₂ leaves) Lungs Diaphragm: * dome-shaped muscle below lungs * contracts and relaxes to control breathing * enlarges thoracic cavity for inspiration

Answer 105

Higher brain functioning (e.g. thought, memories, personality, intelligence, language, vision)

Answer 106

Fine co-ordination of movements (e.g. walking)

Answer 107

Control of functions essential to life which we have no conscious control over Comprised of: The midbrain - centre for several important reflexes (e.g. heart rate, breathing, swallowing, vomiting) The pons - relay between cerebrum and cerebellum The medulla oblongata - visual reflex centre, auditory pathway Reticular formation – controls cyclic activities (e.g. sleep-wake cycle)

Answer 108

Body homeostasis (e.g. temperature, hunger) Comprised of: Thalamus – major sensory relay centre, influences mood and movement Subthalamus – nerve tracts and nuclei Epithalamus – olfactory stimulation, contains pineal gland Hypothalamus – major control centre for homeostasis + regulation of endocrine function

Answer 109

Location: Brain Links nervous and endocrine systems Control centre for homeostasis Controls the pituitary gland

Answer 110

Location: Brain “Master gland” Regulation of metabolic activities of other endocrine glands Releases hormones that regulate other glands (e.g. growth hormone, ADH) Regulation of growth

Answer 111

Location: Brain Produces melatonin (regulates sleep-wake cycle) Maintains seasonal/circadian rhythm

Answer 112

Location: Neck Produces hormones (e.g. thyroxine) that regulate metabolism Induction of cytochrome P450s

Answer 113

Location: behind the thyroid in the neck Regulate calcium and phosphate levels in blood Development of T & B cells

Answer 114

Location: On top of the kidneys Produce hormones for stress response (e.g. adrenaline, cortisol)

Answer 115

Produces insulin and glucagon to regulate blood sugar

Answer 116

Produce oestrogen and progesterone which regulate the menstrual cycle and pregnancy

Answer 117

Produce testosterone which regulates sperm production and male traits

Answer 118

Right atrium – deoxygenated blood from body Right ventricle - deoxygenated blood to lungs Left atrium – oxygenated blood from lungs Left ventricle – oxygenated blood to body

Answer 119

Vena cava – bring deoxygenated blood to the right atrium Pulmonary artery – carry deoxygenated blood to the lungs Pulmonary vein – return oxygenated blood to the left atrium Aorta – carries oxygenated blood from left ventricle to body

Answer 120

Tricuspid Valve – separates right atrium and right ventricle Pulmonary Valve – separates right ventricle and the pulmonary artery Bicuspid (Mitral) Valve – separates left atrium and left ventricle Aortic Valve – separates left ventricle and the aorta

Answer 121

Red blood cells (RBCs) – carry oxygen White blood cells (WBCs) – fight infection Platelets – help blood clot Plasma – fluid portion, carries hormones, nutrients, waste

Answer 122

Arteries – carry blood away from the heart Veins – carry blood toward the heart Capillaries – tiny vessels for gas and nutrient exchange

Answer 123

Removes foreign substances Combats disease Maintains body fluid balance Absorbs fats

Answer 124

Lymph * Clear fluid that leaks out of blood capillaries into tissues * Contains white blood cells, especially lymphocytes Lymphatic Vessels * Network of tubes that carry lymph * One way flow * Similar to veins (have valves to prevent backflow) * Eventually drain into the subclavian veins, returning fluid to the bloodstream / Enter circulatory system via left or right subclavian vein Lymph Nodes * Filter lymph * Contain immune cells that trap and destroy pathogens * Found in clusters (e.g. neck, armpits, groin) Spleen * Filters blood, removes old red blood cells * Stores white blood cells Thymus * Where T cells mature * Most active during childhood, decreases in size in adults Tonsils + adenoids * Trap pathogens from mouth and nose Peyer’s patches * Found in the intestines * Monitor gut bacteria Bone Marrow * Produces lymphocytes and other blood cells

Answer 125

Mouth * Starts digestion with chewing (mechanical) * Tongue forms bolus (ball of food) * Salivary glands - secretes amylase for digestion of carbohydrates into maltose and dextrin Pharynx + esophagus * Pushes food into the stomach via swallowing and peristalsis Stomach * Contains gastric juice comprising of HCl, pepsinogen, lipase, mucus, intrinsic factor * Churns food with acid (HCl) and enzymes (e.g. pepsin) to break down proteins, carbohydrates and fats * Forms chyme (semi-liquid food). Small intestine * Main site of digestion and absorption * 3 parts: duodenum, jejunum, ileum * Villi & microvilli increase surface area for nutrient absorption Large Intestine (Colon) * Absorbs water and electrolytes * Forms and stores faeces Liver * Produces bile to break down fats * Detoxifies blood * Storage of nutrients Gallbladder * Stores and releases bile into small intestine Pancreas * Secretes enzymes (lipase, amylase, protease) and bicarbonate into the duodenum to aid digestion and neutralise stomach acid *Regulation of blood sugar

Answer 126

1. Ingestion involves mouth, pharynx, oesophagus 2. Secretion and digestion * Involves mouth, pharynx, oesophagus, stomach, small intestine * Enzymes are secreted for chemical breakdown of large molecules 3. Absorption * Involves stomach, small intestine, large intestine * Results in smaller soluble molecules and water 4. Assimilation * Utilisation of small molecules by all cells of body 5. Excretion * Rejection of undigested particles + excretion of biochemical waste products

Answer 127

Produces, stores and eliminates urine Filters blood Reabsorbs water, salts, etc. Secretes hormones (adrenaline) Excretes waste products (main source of nitrogen excretion) Regulates blood pH and blood pressure

Answer 128

Kidneys * Filter blood to remove waste, toxins, and extra water * Produce urine and hormones (e.g. erythropoietin, renin) Ureters - thin tubes that transport urine from the kidneys to the bladder via peristalsis Bladder * Muscular sac that stores urine until it's ready to be excreted * Stretch receptors trigger the urge to urinate Urethra * Tube that carries urine from the bladder to outside the body * Shorter in females, longer in males

Answer 129

Testes * Production of spermatozoa (from puberty until old age) * Production of testosterone Vas deferens + Epididymis * There are two of each * Transfer spermatozoa from the testes * Seminal vesicle empties into it Seminal vesicles - secrete seminal fluid for transport of spermatozoa Prostate gland - secrete seminal fluid for transport of spermatozoa Penis * Transfers spermatozoa from male to female * Contains erectile tissue which fill with blood to produce erection

Answer 130

Laryngeal changes - deep voice Growth of facial, pubic and axillary hair Receding hair at temples Increase in muscle and skeletal mass Growth spurt and characteristic male shape of body Increase in sex drive and aggression Increased sebaceous gland secretion (over secretion results in acne)

Answer 131

Ovaries * Production of ova/eggs (from puberty until menopause) * Production of oestrogen and progesterone Fallopian tubes - transfer ova/eggs from the ovaries Uterus - responsible for the nutrition and development of the fertilised egg cell and resulting embryo Vagina - receives spermatozoa Mammary glands - produces milk which provides nutrition for new infant after birth

Answer 132

Development of breasts Characteristic female form + proportions (e.g. narrow shoulders, broad hips) Sex drive Pubic and axillary hair

Answer 133

The process by which the body maintains a stable internal environment despite external changes

Answer 134

Plasma [Na+], [K+], [Ca+] Osmolality pH Body temperature Plasma O2 and CO2 levels Arterial blood pressure

Answer 135

When the response opposes the original stimulus to bring the system back to normal

Answer 136

Hypothalamic osmoreceptors detect changes in body fluid osmotic pressure Changes in the secretion of antidiuretic hormone (induces water reabsorption, therefore less water loss) Stimulation or inhibition of thirst and drinking

Answer 137

When a patient is diabetic excess sugar gets excreted into the urine. This drives the removal of water into the urine to balance the osmotic difference This increases homeostatic regulation of water loss and thus increasing urination frequency and thirst

Answer 138

The hypothalamus

Answer 139

Vasoconstriction = vessels constrict at the surface of the skin → reduction of blood flow to skin → reduction in heat loss Piloerection - traps insulating layer of air next to skin Thermogenesis * Shivering - rapid contraction of muscles generates heat * Activation of mitochondrial activity in brown adipose tissue which generates heat

Answer 140

Vasodilation = vessels dilate at the surface of the skin → increased blood flow to skin → increased heat transfer/loss Sweating - Evaporation of water from skin surface reduces temperature

Answer 141

A drug that occupies receptors and fully activates them (in the same way as the endogenous ligand)

Answer 142

A drug that binds to receptors but produces a lower maximal effect than a full agonist

Answer 143

A drug that binds to receptors without activating them, blocking the action of agonists

Answer 144

A drug that binds to receptors but induces a pharmacological response opposite to that of the agonist (switches off activity)

Answer 145

Reversible drug interactions are mediated by ionic attractions or hydrophobic interactions Irreversible drug interactions are mediated by covalent bonds

Answer 146

In vitro * Most common type of experiment * Use a piece of tissue dissected from an animal (or human) which is kept alive outside the body * Typical responses measured include: tension of a muscle, change in enzyme activity, change in hormone secretion, change in neurotransmitter secretion In vivo * Use a living animal (or human) * Typical responses measured include: increase in blood pressure, reduction in pain threshold, reduction in allergen, induced bronchoconstriction Ex vivo * Use a tissue or organ which has been removed from an animal that has been treated with a drug; the effects the drug has had on organ function are then tested in vitro * Typical experiments measure: whether long-term treatment with a drug induces liver damage or alters some aspect of brain biochemistry

Answer 147

The maximum response (effect) the drug can produce, i.e. the “top” of the concentration-response curve Increasing the concentration of the drug will produce no greater effect

Answer 148

The concentration of a drug that produces 50% of its maximum response Indicates the potency (i.e. sensitivity) of a drug The lower the EC50 the more potent the drug

Answer 149

The ratio between the toxic dose of a drug and the dose producing the desired therapeutic effect The higher the therapeutic index the less chance of the drug producing toxic side-effects in therapeutic use

Answer 150

The equilibrium dissociation constant The molar concentration of a drug needed to occupy 50% of receptors A measure of affinity (i.e. how tightly the receptor holds on to the drug once they come together) A lower Kd = higher affinity

Answer 151

The ability of a drug to activate the receptor once it has bound

Answer 152

EC50 is the the concentration needed to produce 50% of the maximal functional, which describes the potency of an agonist whereas Kd is the concentration at which 50% of receptors are occupied, which describes the agonists affinity for a receptor (i.e. the strength of binding) They will be equal in a simple system where there is no signal amplification and the response is directly proportional to receptor occupancy. However, in many biological systems there are spare receptors or signal amplification mechanisms (e.g. GPCRs with second messengers). In these cases, full activation can occur without all receptors being occupied, so the EC50 is lower than the Kd.

Answer 153

A full agonist reaches a higher maximum response (Emax). A partial agonist has a lower maximum response (Emax). Full agonist produces a steeper, taller curve, whilst a partial agonist produces a shallower curve which plateaus earlier

Answer 154

Receptor antagonism Chemical antagonism * One drug chemically inactivates another * Receptors are not involved * E.g. dimercaprol in arsenic poisoning Pharmacokinetic antagonism * One drug alters the way the body deals with another * Receptors are not involved * E.g. some antacids reduce the absorption of the antiepileptic drug phenytoin from the gut Physiological antagonism * Two drugs act to produce opposing effects, so canceling each other out * E.g. noradrenaline increases heart rate whilst acetylcholine decreases it (in this case both drugs are agonists, but acting on different receptors)

Answer 155

Competitive Non-competitive Reversible Irreversible

Answer 156

Compete with the agonist for the same site on the receptor molecule, but don’t activate Have affinity but zero efficacy

Answer 157

A drug which inhibits the effects of an agonist by acting at a different site on the receptor or another molecule closely associated with it

Answer 158

Reversible competitive antagonists produce a parallel shift to the right of the agonist log concentration vs response curve EC50 changes but Emax remains the same because the action of the antagonist can be overcome by increasing agonist concentration

Answer 159

Irreversible competitive antagonists also produce rightward shift in the agonist log concentration vs response curve. The shift is not parallel, the Emax is lower. This is because inhibition is not overcome by increasing the agonist concentration – it is not surmountable

Answer 160

Maximum binding capacity The total number of receptor sites available for binding in a sample

Answer 161

The ratio of the concentrations of agonist needed to produce the same effect in the presence and absence of antagonist For a reversible competitive antagonists, the dose-ratio should increase linearly with the concentration of the antagonist

Answer 162

The negative log of the antagonist concentration that doubles the EC₅₀ of an agonist/produces a dose ratio of 2 The bigger the pA₂ , the higher the affinity of the antagonist

Answer 163

Construct (log) concentration-response curves for the agonist in the presence of several concentrations of antagonist If there is no parallel shift seen, it is not a reversible competitive antagonist and therefore you cannot continue From the curves read the EC50 values for the agonist in the absence and presence of the different concentrations of antagonist (if using logEC50 calculate by doing inverse e to the power of reading from graph) Calculate the dose ratio for each concentration of antagonist (EC50 in presence of antagonist ÷ EC50 in absence of antagonist) Construct a Schild plot, by plotting log (dose ratio - 1) vs. log antagonist concentration The gradient = 1 The X-axis intercept = log(Kb) pA₂ = negative x-intercept ( - log Kb)

Answer 164

The equilibrium dissociation constant for a competitive antagonist The lower the Kb, the higher the affinity for the receptor, the stronger the antagonist

Answer 165

Whether antagonism is competitive and helps determine pA₂ and Kb which both indicate the affinity of the receptor for the antagonist

Answer 166

Phospholipid bilayer Cholesterol - regulates membrane fluidity Glycoproteins + glycolipids - act as receptors which bind hormones or neurotransmitters triggering responses within the cell Transport proteins

Answer 167

Lipid-soluble molecules Oxygen Nitrogen Carbon dioxide Small uncharged molecules (e.g. urea, glycerol) Water (via aquaporins)

Answer 168

Molecular size (ideal = small) Polarity (ideal = low) Charge (ideal = none) Solubility in oil (ideal = medium) Solubility in water (ideal = medium) Temperature

Answer 169

Simple diffusion Facilitated diffusion Active transport Endocytosis Exocytosis

Answer 170

The net movement of molecules from an area of high concentration to an area of low concentration Passive process - no requirement for energy Spontaneous process driven by an increase in entropy and therefore a decrease in free energy The rate of movement depends on the difference in concentrations (concentration gradient) Non-saturable

Answer 171

1. Molecule must break any bonds/interactions with the aqueous medium (e.g. hydrogen bonds) 2. Enter the lipid region 3. Cross the lipid region via diffusion 4. Leave the membrane at the other side 5. Reform any bonds with the aqueous medium

Answer 172

Non-polar gases (e.g. O2, CO2, N2) Hydrophobic molecules (e.g. steroid hormones, lipid soluble vitamins, small lipid soluble drugs) Urea

Answer 173

The diffusion coefficient (D) Concentration gradient Thickness of the membrane Surface area

Answer 174

J = -D x dC/dx Where * J = flux (rate) * D = diffusion coefficient * C = concentration * x = thickness * dC/dx = concentration gradient OR J = A x D x dC/dx Where A = surface area of membrane

Answer 175

The net movement of molecules from an area of high concentration to an area of low concentration, through the use of specific carrier and/or channel proteins

Answer 176

Carrier proteins - upon binding, undergo conformational changes that allow the molecule to pass through the membrane and be released on the other side Channel proteins - form open pores through the membrane, allowing the free diffusion of the molecule

Answer 177

polar and charged molecules (e.g. carbohydrates, amino acids, nucleosides, and ions)

Answer 178

Uniport - transport one solute at a time Symport * Transports the solute and a co-transported solute at the same time in the same direction * S for same * E.g. uptake of sugars and amino acids into some animal cells is linked to the inward movement of Na+ Antiport * Transports the solute in (or out) and the co-transported solute in the opposite direction * i.e. one goes in the other goes out or vice-versa

Answer 179

The movement of molecules from an area of low concentration to an area of high concentration, working up/against the concentration gradient and thus requiring energy

Answer 180

Primary active transport uses ATP as an energy source Secondary active transport uses an established electrochemical gradient to power the movement (always involves either symport or antiport proteins)

Answer 181

Drug targets E.g. SERT is the target for serotonin reuptake inhibitors (SSRIs) Drug disposition E.g. Breast Cancer Resistance Protein (BCRP) restricts intestinal absorption of anticancer drugs Disease E.g. Cystic fibrosis is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) protein which is an ABC transporter

Answer 182

A type of ABC transporter which transports foreign molecules out of cells Often effects drugs (e.g. anticancer drugs, cardiac glycosides, glucocorticoids, immunosuppressive agents, HIV protease inhibitors)

Answer 183

Break down of molecules Produces/releases more energy than consumed

Answer 184

Formation of molecules Consumes more energy than produced

Answer 185

Nitrogenous base (adenine) Ribose sugar Triphosphate chain (α, β, ɣ)

Answer 186

Catabolism makes ATP → ATP fuels anabolism → Anabolism builds complex molecules → repeat

Answer 187

Substrate-level phosphorylation = involves transferring a high-energy phosphate group from an intermediate directly to ADP Oxidative phosphorylation = involves removal of electrons from NADH and FADH2 which are then passed through an electron transport chain (ETC) to oxygen Photophosphorylation (only occurs in chlorophyll-containing plant cells)

Answer 188

There is electrostatic repulsion between the large, bulky, negatively-charged phosphate groups, which is decreased when ATP is hydrolysed. A free phosphate group enjoys resonance stabilisation, which is not possible in the ATP molecule because of the ester linkages

Answer 189

Produces glucose which is the primary source of energy for cells Glucose can be directed towards: * ATP production * Amino acid synthesis * Glycogen storage * Triglyceride formation

Answer 190

Via GluT transporters (facilitated diffusion) Insulin increases the number of transporters in the membrane which increases the rate of glucose entry into the cell Glucose then undergoes phosphorylation, trapping it inside the cell

Answer 191

1. Glycolysis/Fatty acid oxidation (cytoplasm) 2. Link Reaction (mitochondrial matrix) 3. Krebs Cycle/Citric Acid Cycle/The Tricarboxylic Acid Cycle (mitochondrial matrix) 4. Electron Transfer Chain (ETC)/Oxidative Phosphorylation (membrane of cristae/inner mitochondrial membrane)

Answer 192

Reaction 1 glucose + ATP → glucose-6-phosphate + ADP + H * A phosphate group is transferred from ATP to glucose, making glucose-6-phosphate * Catalysed by the enzyme hexokinase * Utilises a molecule of ATP * Traps glucose inside the cell Reaction 2 glucose-6-phosphate → fructose-6-phosphate * Six-membered pyranose ring becomes a five-membered furanose ring * Catalysed by the enzyme phosphoglucose isomerase Reaction 3 fructose-6-phosphate + ATP → fructose-1,6-bisphosphate + ADP + H * A phosphate group is transferred from ATP to fructose-6-phosphate, producing fructose-1,6-bisphosphate * This step is catalysed by the enzyme phosphofructo-1-kinase (PFK-1) * Utilises another molecule of ATP Reaction 4/5 fructose-1,6-bisphosphate → 2 glyceraldehyde-3-phosphate * Fructose-1,6-bisphosphate splits to form two three-carbon sugars: dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate * This is catalysed by the enzyme aldolase * DHAP is converted into glyceraldehyde-3-phosphate * This is catalysed by the enzyme triphoshpate isomerase (TIM) Reaction 6 2 glyceraldehyde-3-phosphate + 2NAD + 2P → 2 (1,3-bisphosphoglycerate) + 2NADH + 2H * The two molecules of glyceraldehyde-3-phosphate are oxidised and phosphorylated to form 1,3-bisphosphoglycerate * This is catalysed by the enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) * Substrate level phosphorylation * Two molecules of NAD are reduced to NADH Reaction 7 2 (1,3-bisphosphoglycerate) + ADP → 2 (3-phosphoglycerate) + 2ATP * Each 1,3-bisphosphoglycerate molecule donates one of its phosphate groups to ADP to form 3-phosphoglycerate and ATP * Catalysed by the enzyme phosphoglycerate kinase (PGK Reaction 8 2(3-phosphoglycerate) → 2(2-phosphoglycerate) * The two molecules of 3-phosphoglycerate are converted into the isomer, 2-phosphoglycerate * Catalysed by the enzyme phosphoglycerate mutase (PGM) Reaction 9 2(2-phosphoglycerate) → 2PEP(phosphoenolpyruvate) * The two molecules 2-phosphoglycerate lose a molecule of water, forming an enol, phosphoenolpyruvate (PEP) * Catalysed by the enzyme enolase Reaction 10 2PEP + ADP + H → 2Pyruvate + 2ATP * The two PEP molecules readily donate the phosphate group to ADP making 1 molecule of ATP each and forming the end product of glycolysis: pyruvate

Answer 193

Glucose → 2 Pyruvate 2 ATP used 4 ATP produced Net gain = 4 - 2 = 2 ATP 2 NADH generated Total = 2 NADH, 2 ATP, 2 Pyruvate

Answer 194

Glucose uses one molecule of ATP to form glucose-6-phosphate (-1 ATP) Fructose-6-phosphate uses one molecule of ATP to form fructose-1,6-bisphosphate (-1 ATP) Glyceraldehyde-3-phosphate generates one molecule of NADH each (2 x 1 = 2 NADH) 1,3-bisphosphoglycerate generates one molecule ATP each (2 x 1 = 2 ATP) Phosphoenolpyruvate forms one molecule of pyruvate and one molecule of ATP each (2 ATP, 2 Pyruvate) Total = 2 NADH, 2 ATP, 2 Pyruvate

Answer 195

With O₂ : Pyruvate → Acetyl-CoA (in mitochondria) Without O₂ : Pyruvate → Lactate (reduction, in cytosol, reversible by liver)

Answer 196

A carboxyl group is removed from pyruvate in the form of CO₂ The resultant 2 carbon molecule is oxidised by removing a hydrogen atom to form acetate. The hydrogen is picked up by NAD+ to form reduced NAD. The acetyl group is attached to Coenzyme A (CoA) an organic molecule derived from vitamin B5, to form acetyl CoA This process is catalysed by the enzyme pyruvate dehydrogenase (PDH)

Answer 197

1. Acetyl CoA (2C) joins with oxaloacetate (4C) to form citrate (6C) 2. After rearrangement the six-carbon molecule releases two of its carbons as carbon dioxide molecules, producing a molecule of NADH each time 3. The remaining four-carbon molecule undergoes a reaction which produces a molecule of ATP (in some cell GTP instead) 4. The resultant four-carbon molecule is oxidised, forming a molecule of FADH2. 5. Oxaloacetate is regenerated, forming a molecule of NADH

Answer 198

2 x CO2 1 x ATP/GTP 1 x FADH2 3 x NADH For one molecule of glucose → 2 pyruvates → 2 acetyl CoA So Total = 2ATP, 2FADH2, 6NADH

Answer 199

All of the accumulated reduced coenzymes (NADH, FADH2) release the hydrogens which split into protons (H+) and electrons (e-) The electrons are passed down a series of electron carrier proteins embedded in the intermembrane/passed along an electron transport chain, losing energy as they move (FADH2 via Complex II & NADH via complex I) This redox energy is used to pump protons from the mitochondrial matrix into the intermembrane space. This creates a proton gradient (higher concentration in the intermembrane space than the matrix). As a result the protons will move back into the matrix through ATP synthase via chemiosmosis. The diffusion of the hydrogen ions creates a proton motive force which drives the rotation of the ATP synthase enzyme causing the phosphorylation of ADP and therefore formation of ATP Oxygen is the final electron acceptor in the electron transport chain. The oxygen combines with the electrons and the protons to form water.

Answer 200

FADH2 donates electrons via Complex II, whereas NADH donates electrons via Complex I. Complex I is in a higher energy state than complex II so there is more energy for the production of ATP

Answer 201

From Glycolysis: 2 ATP + 2 NADH From Acetyl-CoA formation: 2 NADH From Krebs Cycle: 2 ATP + 6 NADH + 2 FADH2 From ETC: NADH: 3 ATP each → 10 x 3 = 30 FADH2: 2 ATP each → 2 x 2 = 4 Total = 2 + 2 + 30 + 4 = 38 (Some sources state 36 as 2 ATPs are used to move the 2 NADH formed in glycolysis from the cytoplasm into the matrix for the ETC)

Answer 202

Mitochondrial membrane leakage: Protons leak back into the matrix → reduces proton motive force → decreases of ATP synthase activity → lowers ATP production Uncoupling proteins (e.g. dinitrophenol): Provide an alternative pathway for H+ to pass back across the inner mitochondrial membrane → bypass ATP synthase → dissipate energy as heat instead of generating ATP

Answer 203

Dinitrophenol (DNP) acts as an uncoupling agent which dissolves in the inner mitochondrial membrane and carries H+ from the intermembrane space back into the matrix. This means protons bypass ATP synthase, decreasing the proton gradient and therefore the proton motive force. As a result ATP production is reduced and the energy from the ETC is released as heat, which can cause fatal hyperthermia.

Answer 204

Inhibits ATP synthesis by blocking the proton channel, preventing H⁺ from flowing back into the matrix. This halts ATP production via oxidative phosphorylation leading to cellular energy failure and ultimately cell death

Answer 205

The process by which the body converts excess glucose into glycogen for storage Insulin stimulates hepatocytes and skeletal muscle cells to synthesise glycogen

Answer 206

The process by which glycogen stored in hepatocytes is broken down into glucose and released into blood Stimulated by glucagon and epinephrine/adrenaline

Answer 207

The production of glucose from non-carbohydrate sources (glycerol, lactic acid, amino acids) Occurs in the liver Helps maintain blood glucose levels during fasting, starvation, or intense exercise Stimulated by glucagon and cortisol

Answer 208

Lipoproteins = Lipid core + apolipoprotein outer shell

Answer 209

Chylomicrons * Form in the small intestine mucosal epithelia * Transport dietary lipids to adipose tissue VLDL (Very Low-Density Lipoproteins) * Formed in hepatocytes (liver) * Transport endogenous lipids to adipocytes LDL (Low-Density Lipoproteins) * "bad cholesterol” * Delivered to body cells for repair and synthesis * Can deposit cholesterol to form fatty plaques HDL (High-Density Lipoproteins) * "good cholesterol" * Removes excess cholesterol from body cells + blood and delivers them to the liver for elimination

Answer 210

Three allelic variants: E2, E3, E4 Each have varying degrees of risk for the onset of AD: E4 > E3 > E2 E4/E4 genotype = High risk E2/E2 genotype = Low risk

Answer 211

Dietary intake Endogenous synthesis in hepatocytes

Answer 212

Inhibit 3-Hmg-CoA reductase which is an enzyme found in the liver involved in the cholesterol synthesis pathway.

Answer 213

Oxidised to provide ATP Stored in adipose tissue if not needed for ATP production Lipid catabolism (lipolysis / fatty acid oxidation / β-oxidation) * Breaks triglycerides → glycerol + fatty acids * Generates acetyl-CoA, which enters the Krebs cycle to produce ATP * Occurs in mitochondria * Promoted by epinephrine/norepinephrine Lipid anabolism (lipogenesis / fatty acid synthesis): * Converts glucose/amino acids → fatty acids * Occurs in cytosol of hepatocytes and adipocytes * Happens in calorie surplus (when more calories are consumed than needed for ATP production)

Answer 214

Caffeine * Stimulates β-oxidation * Commonly found in high-performance energy gels used by runners Mildronate (meldonium) - Inhibits fatty acid oxidation Valproate - Inhibits fatty acid oxidation

Answer 215

The synthesis of new proteins in ribosomes, used for enzymes, hormones, and structural proteins

Answer 216

Excess amino acids cannot be stored and are: Oxidised to produce ATP or intermediates for metabolic cycles Converted into glucose (via gluconeogenesis) Converted into fatty acids (via lipogenesis) and stored as triglycerides in adipose tissue

Answer 217

During prolonged starvation, fasting, or low-carb intake

Answer 218

They must undergo deamination - i.e. removal of the amino group

Answer 219

Produces ammonia (NH₃), which is toxic and converted into urea by the liver and excreted in urine by the kidneys

Answer 220

The process where an amino group (-NH₂) is transferred from one amino acid to a keto acid to form a new amino acid Catalysed by enzymes called transaminases or aminotransferases E.g. ALT (alanine aminotransferase), AST (aspartate aminotransferase) Requires the coenzyme pyridoxal phosphate (PLP), derived from vitamin B6

Answer 221

Synthesise amino acids that are not obtained from the diet (non-essential amino acids) Converts amino acids into intermediates that can enter the Krebs cycle or be used in gluconeogenesis

Answer 222

Glucose 6-phosphate Pyruvate Acetyl-CoA

Answer 223

Produced shortly after glucose enters the cell “traps” the glucose inside the cell Has many uses: Glycolysis (important for energy/ATP production) Synthesis of glycogen (energy stores) Release of glucose into blood stream Synthesis of nucleic acids Synthesis of UDP-glucuronic acid for Phase II metabolism

Answer 224

The end product of glycolysis Enters the Krebs cycle, in the presence of sufficient oxygen (oxidative phosphorylation) When there is a lack of oxygen can be used for: * Production of lactic acid * Production of alanine (transamination) * Gluconeogenesis

Answer 225

The entry molecule into the Krebs cycle Used to synthesise fatty acids and cholesterol (lipogenesis)

Answer 226

It's the period during and shortly after eating when ingested nutrients (glucose, amino acids, triglycerides in chylomicrons) enter the bloodstream

Answer 227

Glucose is readily available and used for ATP production

Answer 228

It is stored in hepatocytes, adipocytes, and skeletal muscle cells.

Answer 229

Pancreatic beta cells release insulin which promotes entry of glucose and amino acids into cells

Answer 230

About 4 hours after eating, when nutrient absorption is complete

Answer 231

Blood glucose levels starts to fall Energy is derived from stored fuels

Answer 232

Glucose production Glucose conservation

Answer 233

Breakdown of liver glycogen Lipolysis Gluconeogenesis (from lactate and/or amino acids)

Answer 234

Oxidising fatty acids, lactate, amino acids and ketone bodies Breaking down muscle glycogen

Answer 235

Calcium Copper Iodine Iron

Answer 236

Fat-soluble vitamins * Vitamins A, D, E, and K Water-soluble vitamins * Vitamins B1 (thiamine), B2 (riboflavin), B3 (niacin), B5 (pantothenic acid), B6, B7 (biotin), B9, B12 (cobalamin) * Vitamin C (L-ascorbic acid)

Answer 237

A disorder of energy usage and storage Diagnosed by the clustering of at least three of the following: * Central obesity * High blood pressure * High blood sugar * High serum triglyceride * Low HDL

Answer 238

Genetic defects in enzyme-encoding genes

Answer 239

Glucose-6-phosphatase deficiency (carbohydrate metabolism disorder)

Answer 240

Glycogen debranching enzyme deficiency (carbohydrate metabolism disorder)

Answer 241

Glycogen branching enzyme deficiency (carbohydrate metabolism disorder)

Answer 242

Autosomal recessive amino acid metabolism disorder Deficiency in phenylalanine hydroxylase (PAH) Causes build-up of Phe, which competes for the LNAA transporter in the blood-brain-barrier, reducing entry of key amino acid used to synthesise neurotransmitters and neuronal proteins Reduces Tyr synthesis – reduced dopamine, norarenaline and adrenaline synthesis

Answer 243

Treated with a diet low in foods containing phenylalanine and aspartame (which is metabolised into Phe)

Answer 244

Intellectual disability Seizures Behaviour problems Microcephaly

Answer 245

Medium-chain acyl-coenzyme A dehydrogenase deficiency An autosomal recessive lipid metabolism disorder Prevents breakdown of fatty acids into acetyl-CoA Managed by avoiding fasting and using glucose supplements during illness

Answer 246

Frequent urination Increased thirst Increased hunger Diabetic ketoacidosis

Answer 247

Cardiovascular disease Kidney disease Foot ulcers

Answer 248

Type 1 * Pancreatic failure to produce insulin due to loss of beta-cells * No known cause * Treated using insulin injections Type 2 * Insulin resistance * Can lead to lack of insulin * Caused by obesity and insufficient exercise * Treated using diet Gestational diabetes - occurs in pregnant women

Answer 249

When the body shifts to fat metabolism (fatty acid oxidation) due to insulin deficiency Produces ketone bodies (β-hydroxybutyrate (main) + Acetoacetate) Occurs mainly in type 1 diabetes

Answer 250

Nausea Vomiting Thirst Excessive urination Kussmaul breathing (a deep, rapid, and labored breathing pattern) Fruity breath Cerebral oedema (in children) Coma Death

Answer 251

Mild * pH 7.2 – 7.3 * Serum bicarbonate 10 – 15 mM * Person is alert Moderate * pH 7.1 – 7.2 * Serum bicarbonate 5 – 10 mM * Person is mildly drowsy Severe * pH < 7.1 * Serum bicarbonate < 5 * Patient is in a coma

Answer 252

IV fluids IV insulin Potassium (replacement of potassium lost due to osmotic diuresis)

Answer 253

Fats Oils Waxes Phospholipids Glycolipids Steroids

Answer 254

Glycerol + 3 fatty acids = Triacylglycerol (Triglyceride) Ester bond

Answer 255

Saturated (e.g. stearic acid) Monounsaturated (e.g. oleic acid) Polyunsaturated (e.g. - E.g. Linoleic Acid, Omega-3 and Omega-6)

Answer 256

Saturated: * no double bonds * form straight chains * tightly packed + strong intermolecular forces → high melting points → solid at room temperature * found in butter, animal fats Unsaturated * Contain double bond(s) * Mono = one double bond * Poly = multiple double bond * Kink/bending → lower melting points → liquid at room temp

Answer 257

Cis configuration - creates more fluidity Trans fats are linked to coronary heart disease

Answer 258

Esters formed from long-chain fatty acids + alcohols No double bonds High melting points Chemically inert Provide a waterproof coating on the surfaces of many organisms

Answer 259

glycerol 2 fatty acids a phosphate group which is usually linked to a small ionic nitrogen-containing group (e.g. choline, serine, ethanolamine)

Answer 260

Comprised of: glycerol + 2 fatty acids + a sugar Involved in cell recognition and cell signalling

Answer 261

Organic compounds containing four fused rings Includes: * Cholestanes (e.g. Cholesterol) * Estranes (e.g. Estradiol) * Androstanes (e.g. Testosterone) * Pregnanes (e.g. Progesterone)

Answer 262

Structural role in membranes Precursor of steroid hormones (e.g. corticosteroids from adrenal cortex) Vitamin D synthesis Bile acid synthesis

Answer 263

Energy storage Carrier for fat-soluble vitamins (A, D, E, K) Membrane fluidity + signalling Immune response (e.g. via Eicosanoids)

Answer 264

Based on the position of the OH group on the last chiral carbon D-isomer: OH group is on the right L-isomer: OH group is on the left

Answer 265

Simple sugars made of a single sugar unit. E.g. glucose, fructose, galactose, ribose

Answer 266

Carbohydrates made of two monosaccharide units linked by a glycosidic bond E.g. Sucrose = glucose + fructose Lactose = glucose + galactose

Answer 267

Carbohydrates made of many monosaccharide units linked by glycosidic bonds E.g. starch, glycogen, cellulose

Answer 268

Both are stereoisomers - i.e. have same molecular formula and connectivity but different spatial arrangement Enantiomers are non-superimposable mirror images while diastereomers are not mirror images Enantiomers have identical physical properties (except for optical rotation), but diastereomers do not

Answer 269

A molecule with n chiral centers has 2ⁿ stereoisomers

Answer 270

They can form cyclic structures via an internal reaction between the carbonyl group and a hydroxyl group

Answer 271

A new chiral center at carbon 1, known as the anomeric carbon

Answer 272

α-anomer: OH on C1 is down, opposite to CH₂OH on C5 β-anomer: OH on C1 is up, same side as CH₂OH

Answer 273

A hemiacetal forming a pyranose (6-membered ring)

Answer 274

A monosaccharide that contains an aldehyde group (-CHO) at carbon 1 E.g. glucose

Answer 275

A monosaccharide that contains a ketone group (C=O) E.g. fructose

Answer 276

A hemiketal, forming a furanose (5-membered ring)

Answer 277

O-linked * Sugar is linked to another molecule via oxygen (OH + OH) N-linked * Sugar is linked via a nitrogen atom (OH + NH)

Answer 278

Energy source + storage (e.g. glucose, glycogen) Membrane structure + recognition and signaling (e.g. glycolipids) Nucleic acid structure (ribose in RNA, deoxyribose in DNA) Protein modification: * N-linked glycosylation (to Asn in Asn-X-Ser/Thr motif) * O-linked glycosylation (to Ser or Thr)

Answer 279

As drugs themselves E.g. streptomycin (antibiotic) In drug delivery systems * Modified carbohydrates (e.g. cyclodextrins) improve solubility and bioavailability As excipients E.g. Lactose and starch are used as binders + fillers As conjugates for enhanced targeting or uptake Vaccines Diagnostics * Carbohydrate markers used in blood tests Scaffold in drug discovery

Answer 280

Enzymes are often drug targets Affect drug metabolism

Answer 281

metal ions - Zn2+ , Mg2+ , Mn2+

Answer 282

Nicotinamides - e.g. NADP(H), NAD(H) Flavins - e.g. FMN, FADs, prFMN

Answer 283

An enzyme without a cofactor

Answer 284

An enzyme with a cofactor

Answer 285

Van der Waals interactions Hydrogen bonding Electrostatic interactions Entropic contributions due to “hydrophobic effect”

Answer 286

Oxidoreductases (EC1) Transferases (EC2) Hydrolases (EC3) Lyases (EC4) Isomerases (EC5) Ligases (EC6) Translocases (EC7)

Answer 287

Enzymes which catalyse oxidation and/or reduction reactions E.g. dehydrogenases, reductases

Answer 288

Enzymes which catalyse the transfer of a functional group/moiety from donor to acceptor E.g. aminotransferases, methyltransferases, prenyltransferases

Answer 289

Enzymes which catalyse the cleavage of various bonds not via hydrolysis and oxidation E.g. ammonia lyases

Answer 290

Enzymes which catalyse isomerisation within a single molecule

Answer 291

Enzymes which link two molecules together at a specific site, usually with covalent bonds E.g. C-N ligases, DNA ligases

Answer 292

Enzymes which mediate the movement of molecules/ions across cell membranes or their separation within a membrane E.g. ADP/ATP translocase

Answer 293

States that an enzyme's active site has a specific, rigid shape that exactly matches the shape of its substrate - just like a key fits into a specific lock Highly stereospecific

Answer 294

States that when a substrate begins to bind, it induces a conformational change in the enzyme that results in a more precise fit Takes into account the flexibility of proteins

Answer 295

Acid-Base Catalysis Covalent Catalysis Electrostatic Catalysis

Answer 296

Ser 195 * The serine -OH group acts as a nucleophile and attacks the carbonyl carbon of the peptide bond of the substrate His 57 * The histidine nitrogen accepts the hydrogen in the OH group of serine hence coordinating the attack of the peptide bond Asp 102 * Aspartic acid contains a carboxyl group which hydrogen bonds with the more electronegative histidine Nitrogen

Answer 297

D169 - deprotonates amines Y177 - anchors ketone group

Answer 298

Temperature pH Enzyme concentration Substrate concentration Presence of inhibitors or activators

Answer 299

Enzyme activity increases with temperature up to an optimum. Beyond the optimum, denaturation occurs, where the enzyme loses its structure and therefore function

Answer 300

Each enzyme has an optimal pH (e.g., pepsin ~pH 2, amylase ~pH 7) Extremes of pH will denature the enzyme and so destroy activity This is because they are made of proteins containing many ionisable groups, which will exist in a whole series of different states of ionisation depending on the pH This will have its greatest effect in the active site where ionization may affect shape and any ionic binding of substrate The ionization of the substrate(s) must also be considered

Answer 301

Describes how the reaction rate varies with substrate concentration v = Vmax[S] ÷ Km + [S] Where * v = V0 = initial reaction rate * Vmax = maximum reaction rate (when enzyme is saturated) * Km = Michaelis constant (substrate concentration at half Vmax)

Answer 302

The formation of the enzyme-substrate (ES) complex is reversible The concentration of ES reaches a steady state (doesn't change over time)

Answer 303

Plot V₀ vs. [S]

Answer 304

At relatively low concentrations of substrate, V0 increases almost linearly with an increase in [S] At higher substrate concentrations, V0 increases by smaller and smaller amounts in response to increases in [S] Finally, a point is reached beyond which increases in V0 are vanishingly small as [S] increases. This plateau-like V0 region is close to the maximum velocity, Vmax

Answer 305

The substrate concentration at which half the enzyme active sites are occupied by the substrate Indicates substrate affinity Lower Km = higher affinity (and tighter binding)

Answer 306

The number of substrate molecules converted to product in a given unit of time on a single enzyme molecule when the enzyme is saturated with substrate The turnover number

Answer 307

Kcat ÷ Km A measure of catalytic efficiency

Answer 308

Michaelis-Menten Plot = V₀ vs [S] Lineweaver-Burke Plot = 1/V₀ vs 1/[S] Hanes-Woolf Plot = [S]/V₀ vs [S] Eadie-Hofstee Plot = V₀ vs V₀/[S]

Answer 309

1/V₀ vs 1/[S] Gradient = Km/Vmax y-intercept = 1/Vmax x-intercept = -1/Km

Answer 310

[S]/V₀ vs [S] Gradient = 1/Vmax y-intercept = Km/Vmax x-intercept = -Km

Answer 311

V₀ vs V₀/[S] Gradient = -Km y-intercept = Vmax x-intercept = Vmax/Km

Answer 312

The enzyme which catalyses the first step in the metabolic scheme The enzyme which catalyses the rate-limiting step The enzyme which is functionally the most critical

Answer 313

Reversible competitive Reversible uncompetitive Reversible non-competitive (mixed) Irreversible

Answer 314

Inhibitor competes with substrate at active site Increases Km Vmax unchanged E.g. Captopril (ACE inhibitor), Trimethoprim

Answer 315

Inhibitor binds only after substrate binds → traps enzyme in ES form Decreases both Km and Vmax E.g. Finasteride, Methotrexate

Answer 316

Inhibitor binds to enzyme or ES complex at a different site Both inhibitor and substrate can bind to the enzyme simultaneously Vmax decreases Km unchanged or variable E.g. Etoposide, Tacrine

Answer 317

Forms covalent bond with enzyme, permanently inactivating it E.g. Penicillin, Diisopropyl fluorophosphate (DIFP)

Answer 318

Dissociation constant of enzyme-inhibitor complex Difference in gradients = 1 + [I]/Ki Lower Ki = more potent inhibitor (tighter binding)

Answer 319

Dissociation constant for enzyme-substrate-inhibitor complex Difference in gradients = 1 + [I]/Ki' Lower Ki = more potent inhibitor (tighter binding)

Answer 320

1. Measure initial rates, v at varying substrate concentrations [S], with and without inhibitor 2. Construct a Lineweaver-Burk Plot (1/v vs 1/[S]) using the data obtained For: Competitive - Lines intersect at y-axis (same Vmax, increased Km) Uncompetitive - Parallel lines (lower Vmax and Km) Mixed - Lines intersect left of y-axis (lower Vmax, variable Km) For all increasing [I] = steeper/lower gradient (upwards)

Answer 321

Composed of: * An amino group * Carboxylic acid * Hydrogen atom * R-group/ side chain which is variable (can be non polar, polar uncharged, polar charged, etc.)

Answer 322

Non polar aliphatic amino acids E.g. Glycine, Alanine, Proline, Valine, Leucine, Isoleucine, Methionine Aromatic amino acids E.g. Phenylalanine, Tyrosine, Tryptophan Polar uncharged amino acids E.g. * Serine (hydroxyl group) * Threonine (hydroxyl group) * Asparagine (amide group) * Glutamine (amide group) * Cysteine (sulfhydryl group - a weak acid, mostly uncharged at neutral pH, can form disulphide bridges) Positively charged amino acids E.g. Lysine, Arginine, Histidine Negatively charged amino acids E.g. Aspartate (carboxyl group), Glutamate (carboxyl group)

Answer 323

The carboxylic acid becomes protonated, and the molecule is positively charged

Answer 324

The amino group loses its proton, making the molecule negatively charged

Answer 325

The pH at which an amino acid has no net charge and exists as a zwitterion (positively charged amino group and negatively charged carboxyl group) pI = (pKa1 + pKa2) ÷ 2

Answer 326

A molecule with both a positive and negative charge but an overall neutral charge

Answer 327

Two one for the α-carboxyl group and one for the α-amino group E.g. glycine

Answer 328

Three one for the α-carboxyl group, one for the α-amino group and one for the side chain (R group) E.g. lysine, arginine, glutamic acid, aspartic acid

Answer 329

Primary Secondary Tertiary Quaternary

Answer 330

The number, type and sequence of amino acids joined together by strong covelant peptide bonds in a condensation reaction to form a polypeptide chain

Answer 331

The amino group of one amino acid displaces the hydroxyl group of another

Answer 332

The amino group of one amino acid acts as a nucleophile to displace the hydroxyl group of another amino acid

Answer 333

A covalent bond formed between the carboxyl group of one amino acid and the amino group of another

Answer 334

The lone pair on the nitrogen is delocalised onto the carbonyl oxygen, creating partial double bond character

Answer 335

No, rotation around the peptide bond is not permitted due to partial double bond character

Answer 336

The trans form which is more stable (exception = proline)

Answer 337

The end with a free NH₂ group, not involved in a peptide bond

Answer 338

The end with a free COOH group, not involved in a peptide bond

Answer 339

From the N-terminus to the C-terminus

Answer 340

The three dimensional structure determined solely by hydrogen bonds formed between the carbonyl oxygen and the amino nitrogen

Answer 341

A right-handed coil where the C=O group of one amino acid hydrogen bonds with the NH group four residues ahead

Answer 342

Small hydrophobic residues like alanine and leucine due to low steric hindrance

Answer 343

Proline: No rotation around N–Cα bond Glycine: Lacks an R group, allowing other conformations

Answer 344

A secondary structure where hydrogen bonds form between NH and CO groups of adjacent polypeptide chains

Answer 345

Parallel: Chains run in the same direction Antiparallel: Chains run in opposite directions and can form loops or U-turns

Answer 346

Larger bulky residues (e.g. valine, isoleucine, phenylalanine) which can stabilise the extended structure through hydrogen bonding and packing interactions

Answer 347

Short regions allowing the protein backbone to change direction, often connecting α-helices and β-sheets.

Answer 348

A 4-residue turn stabilised by a hydrogen bond between the CO of residue 1 and NH of residue 4.

Answer 349

Proline at position 2 (rigidity) Glycine at position 3 (flexibility)

Answer 350

The three-dimensional structure is determined by interactions between R groups and their properties

Answer 351

Hydrogen bonds (between polar R groups) Ionic bonds (between charged R groups) Hydrophobic interactions (non-polar side chains) Electrostatic interactions (e.g. aspartate, lysine) Van der Waals forces Disulfide bridges (e.g. cystine)

Answer 352

Covalent bonds between sulfur atoms of two cysteine residues Can be intramolecular (within one polypeptide chain) or intermolecular (between chains)

Answer 353

Fibrous proteins Globular proteins

Answer 354

Insoluble (hydrophobic exterior) Made from a single secondary structure Much less compact than globular proteins Play important roles in providing structural rigidity and in contractile movement E.g. Collagen, Keratin, Fibrin, Myosin

Answer 355

Hydrophobic side chains fold inward (forming water-free pockets) Polar side chains face outward (hydrophilic exterior) Function as enzymes, transporter, antibodies, etc. E.g. Hemoglobin, Amylase, Insulin, Immunoglobulins

Answer 356

When a protein contains more than one polypeptide chain (subunits) Can be identical subunits (homo) or different (hetero) Not all proteins have a quaternary structure

Answer 357

Heat pH extremes Organic solvents (e.g. alcohols) - interfere with hydrophobic interactions Reducing agents - convert disulphides into thiols Detergents - disrupt hydrophobic interactions Salts - causes aggregation and precipitation UV radiation Urea

Answer 358

Signalling (hormones) Catalysis (enzymes) Genetics (e.g. histones, transcription factors) Defence (antibodies) Movement (e.g. actin, myosin) Structure (e.g. collagen, elastin) Transport (e.g. membrane proteins, myoglobulin, albumin, haemoglobin)

Answer 359

Globular protein ~ 153 amino acids Monomeric (8 α-helices) Contains a heme prosthetic group in a hydrophobic pocket which binds oxygen

Answer 360

Stores and transports oxygen within muscles

Answer 361

Globular protein Highly water-soluble Contains multiple hydrophobic pockets for binding

Answer 362

Maintains osmotic pressure in blood Acts as a buffer for pH and ions Transports fatty acids, hormones (e.g. thyroxine), drugs (e.g. warfarin), bilirubin, etc.

Answer 363

Globular proteins Y-shaped glycoproteins Consist of 4 polypeptide chains, which are connected by disulphide bonds: * 2 heavy chains * 2 light chains

Answer 364

Controls the movement of substances in and out of the cell

Answer 365

Controls and regulates the activities of the cell (e.g. growth, metabolism, etc.) Carries genetic information (DNA)

Answer 366

Nucleolus * contains chromatin, proteins and RNA * synthesises ribosomes Chromatin - tangled form of DNA bounded to histones (proteins which act like spools for thread) Nuclear membrane/envelope - a double membrane which controls exchange Nuclear Pores - allow mRNA and ribosomes to pass through Nucleoplasm - full of chromatin, contains chromosomes

Answer 367

The site of protein synthesis

Answer 368

Function: Folds and processes proteins made on the ribosomes Strcuture: A series of flattened sacs enclosed by a membrane (called cisternae) with ribosomes on the surface

Answer 369

Structure: a network of tubules Function: produces and processes lipids

Answer 370

Site of aerobic respiration, producing ATP

Answer 371

Double Membrane: * Inner Membrane - contains folds/finger-like projections called Cristae which increases surface area * Outer membrane - more permeable, contains proteins called porins to form aqueous channels Matrix - contains the enzymes needed for respiration

Answer 372

Function: processes, modifies and packages proteins and lipids + produces lysosomes Structure: a series of fluid-filled, flattened and curved sacs with vesicles surrounding the edges

Answer 373

Microfilaments * provides shape and structure to the cell * facilitates cell division and muscle contraction Intermediate filaments * provides structural stability to the cell * anchors organelles in place Microtubules * component of flagella, cilia, and centrioles * facilitate cell division

Answer 374

Function: breaks down cellular debris Structure: membrane-bound vesicles which contain lysozyme, a hydrolytic enzyme

Answer 375

Produce the spindle fibres during cell division

Answer 376

generate and destroy hydrogen peroxide away from the rest of the cell where it would cause damage

Answer 377

By their shape (squamous, cuboidal, columnar) and arrangement (simple, stratified, pseudostratified)

Answer 378

Squamous: Flat and sheet-like Cuboidal: Cube-shaped (equal width, height, depth) Columnar: Tall and column-like (taller than wide)

Answer 379

Simple: One layer of cells Stratified: Multiple layers Pseudostratified: One layer that appears layered due to cell height variation

Answer 380

Mucous membrane: * Contains goblet cells, which secrete mucus * Lines external cavities (e.g. respiratory and digestive tract) Serous membrane: * Made up of simple squamous epithelium/ * Lines internal cavities (e.g. pleura)

Answer 381

Location: alveoli, blood vessels, lymphatics, serous membranes Function: allows substances to pass through by diffusion and filtration + secretes lubricating substances

Answer 382

Location: glandular tissue, kidney tubules Function: absorption and secretion

Answer 383

Location: bronchi, uterus, digestive tract Function: protection, absorption, secretion of mucus and enzymes Can be ciliated

Answer 384

Location: esophagus, mouth, vagina, skin Function: protection against abrasion, pathogens, and chemicals

Answer 385

Location: sweat glands, salivary glands, mammary glands Function: protection and secretion

Answer 386

Location: male urethra, salivary gland ducts Function: protection and secretion

Answer 387

Location: trachea, upper respiratory tract, male reproductive ducts Function: mucus secretion and movement Usually ciliated

Answer 388

Stratified cuboidal cells that flatten (squamous-shaped) when stretched Location: the urinary tract and bladder Function: Stretch readily to accommodate the different volume of liquids

Answer 389

Dead epithelial cells which are devoid of the nucleus and cytoplasm and filled with keratin Function: protection against abrasion

Answer 390

Tight junctions Adherens Junctions Desmosomes Gap junctions Hemidesmosomes

Answer 391

Structure: composed of proteins called claudins and occludins which are arranged into strands that "stitch" adjacent cells together Function: * Forms an impermeable barrier that prevents the passage of molecules and ions through the space between adjacent cells * Maintains the polarity of the cells (apical and basolateral) * Regulates selective permeability (e.g. in the intestines and blood-brain barrier)

Answer 392

Structure: formed by cadherin proteins that link to the actin cytoskeleton inside the cell and extend to the neighbouring cell Function: * Provide mechanical strength * Anchor cells together and allowing them to function as a unit, especially in tissues that experience stress (e.g. epithelial layers)

Answer 393

Structure: composed of proteins called cadherins (desmoglein and desmocollin) linked to intermediate filaments, forming strong button-like adhesions between cells Function: * Pin adjacent cells together * Resists mechanical stress, especially in tissues that stretch (e.g. skin, cardiac muscle)

Answer 394

Structure: comprised of of connexin proteins that form channels connecting adjacent cells Function: * Allow direct communication between cells by permitting the passage of ions, small molecules and electrical signals * Important for tissue coordination (e.g. in cardiac and smooth muscle)

Answer 395

Structure: comprised of integrin proteins (α6β4 integrins) that connect the cell’s intermediate filaments (keratin) to the basement membrane Function: attach epithelial cells to extracellular matrix for structural support

Answer 396

Ground substance - a jelly like substance made of glycosaminoglycans Protein fibers: * Collagen * Reticular fibres * Elastic fibres

Answer 397

Fibroblasts - synthesise extracellular matrix components like collagen and ground substance Macrophages - engulf pathogens and debris (immune defence) Plasma cells - produce antibodies Mast cells - release histamine and other mediators during allergic and inflammatory reactions Adipose cells: * Store energy as fat * Provide insulation and cushioning

Answer 398

Areolar Adipose Reticular

Answer 399

Location: under the skin + around blood vessels, nerves and organs Structure: loose, irregular arrangement of fibres + a variety of cells (fibroblasts, macrophages, mast cells) Function: provides cushioning, support, and flexibility to tissues and organs + immune defence

Answer 400

Location: under the skin + around organs Two types - white adipose tissue + brown adipose tissue Composed mainly of adipocytes Function: * Insulation/maintaining body temperature * Provides cushioning and protection to organs * Stores energy

Answer 401

Location: tendons (connecting muscles to bones) + ligaments (connecting bones at joints) Structure: * Composed of parallel bundles of collagen fibers with fibroblasts squeezed between them * The alignment of the fibres provides tensile strength in one direction Function: Provides strong resistance to pulling forces in one direction

Answer 402

Location: the dermis of the skin + organs of the digestive tract Structure: * Irregularly arranged collagen fibers that are thicker and interwoven, with fibroblasts scattered throughout * The disordered fiber arrangement allows resistance to tension in multiple directions Function: Provides strength and support in tissues that experience stress from many directions, helping to prevent tearing or damage

Answer 403

Compact (outer layer) Spongy (inner layer containing bone marrow)

Answer 404

Skeletal * Location: Skeletal muscle * Voluntary contraction * Structure: Long cylindrical fibres, highly striated * Function: Movement + maintenance of posture + heat production Smooth * Location: Walls of hollow organs + blood vessels * Involuntary contraction * Structure: Spindle shaped fibres, nonstriated Function: Peristalsis, contraction + relaxation of vessels and bronchi Cardiac * Location: Heart * Involuntary contraction * Structure: Short branching fibres, finely striated * Function: Circulation of blood

Answer 405

1. Nerve impulse arrives at the neuromuscular junction, releasing acetylcholine (ACh) 2. ACh binds to receptors on the muscle cell membrane, triggering an action potential 3. The action potential travels down the T-tubules, stimulating the sarcoplasmic reticulum to release calcium ions (Ca²⁺) 4. Calcium binds to troponin, causing a shift in tropomyosin, which exposes the binding sites on actin 5. Myosin heads bind to actin, forming cross-bridges 6. Using energy from ATP, the myosin head performs a power stroke, pulling actin filaments inward and shortening the sarcomere 7. A new ATP molecule binds to myosin, causing it to detach from actin and reset. 8. This cycle repeats as long as calcium and ATP are present, leading to muscle contraction. 9. When stimulation ends, calcium is pumped back into the sarcoplasmic reticulum, tropomyosin re-covers binding sites, and the muscle relaxes

Answer 406

1. Stimulation occurs via ANS or local factors (e.g. stretch) 2. This causes an influx of calcium ions (Ca²⁺) into the smooth muscle cell from the extracellular space or sarcoplasmic reticulum 3. Ca²⁺ binds to a protein called calmodulin 4. The calcium–calmodulin complex activates myosin light chain kinase (MLCK) 5. MLCK phosphorylates myosin, allowing it to bind to actin and initiate contraction 6. Relaxation occurs when calcium levels fall, MLCK activity stops, and myosin is dephosphorylated by myosin phosphatase Contraction is slower and more sustained than in skeletal muscle

Answer 407

Controlled by autonomic nervous system Sympathetic Innervation (e.g. blood vessels, bronchi): 1. Preganglionic neurons release ACh onto nicotinic receptors in sympathetic ganglia 2. Postganglionic neurons release noradrenaline/ norepinephrine 3. Noradrenaline binds to adrenergic receptors on smooth muscle: α₁ receptors (e.g. in blood vessels) → Gq pathway, increases IP₃ → increases Ca²⁺ release → increases contraction β₂ receptors (e.g. in bronchi) → Gs pathway, increases cAMP → inhibits MLCK → relaxation Parasympathetic Innervation (e.g. gut, bladder): 1. Preganglionic neurons release acetylcholine (ACh) onto nicotinic receptors in autonomic ganglia 2. Postganglionic neurons release ACh onto muscarinic M3 receptors on smooth muscle 3. This activates Gq pathway, increases IP₃ , which increases Ca²⁺ release from the sarcoplasmic reticulum 4. Ca²⁺ binds calmodulin → activating MLCK → increased contraction

Answer 408

Controlled by the autonomic nervous system Sympathetic Innervation: 1. Innervation of the SA node is via the cardiac nerve which releases noradrenaline 2. Noradrenaline binds to β1 adrenergic receptors which activates Gs pathway → increases cAMP which: * Activates PKA → increases Ca²⁺ release → positive inotropy, i.e. greater force of contraction * Speeds up depolarisation → positive chronotropy, i.e. faster rate - more beats per second Parasympathetic Innervation 1. Innervation of the SA node is via the vagus nerve which releases acetylcholine 2. Acetylcholine binds to M2 muscarinic receptors which activates Gi pathway → inhibits adenylate cyclase + opens K+ channels → increases time taken to reach the threshold for an action potential → negative chronotropy, i.e. slower rate

Answer 409

Reproductive cells (sperm in males, ova in females) Function: * carry genetic information * involved in sexual reproduction * combine during fertilisation to form a zygote

Answer 410

Head containing the nucleus with tightly packed DNA - delivers paternal genetic material to the ovum Acrosome - contains enzymes which help penetrate the ovum's outer layers during fertilisation Midpiece is packed with mitochondria - produces ATP to power movement of the tail Tail (flagellum) - long, whip-like structure which propels the sperm forward for mobility through the female reproductive tract

Answer 411

Nucleus - contains maternal DNA Cytoplasm - rich in nutrients and organelles which supports early development after fertilisation Zona pellucida - glycoprotein layer surrounding the cell membrane which protects the ovum and regulates sperm binding Corona radiata - layer of follicular cells surrounding the zona pellucida which supplies nutrients and supports the ovum's journey through the fallopian tube

Answer 412

The release of a mature egg from the ovary, triggered by a surge in luteinising hormone (LH), typically around day 14 of the menstrual cycle

Answer 413

When a sperm cell penetrates the ovum’s membrane, combining genetic material to form a diploid zygote, usually in the fallopian tube

Answer 414

The process by which a fertilised egg (zygote) develops into an embryo, involving cell division + differentiation and the formation of early tissues and organs

Answer 415

Undifferentiated cells that can divide and develop into different types of specialised cells

Answer 416

Totipotent - can form all cell types including placenta Pluripotent - can form any cell of the body (not placenta) Multipotent - can form limited cell types (e.g. blood cells) Unipotent - can form only one cell type

Answer 417

The process by which all blood cells are formed from haematopoietic stem cells in the bone marrow

Answer 418

Structure: biconcave, lacking nuclei, contain haemoglobin Function: transport oxygen

Answer 419

A type of WBC that engulf and destroy pathogens through phagocytosis

Answer 420

Fight larger parasites Modulate allergic inflammatory responses

Answer 421

Regulate allergic inflammatory response Release histamine

Answer 422

B cells - produce antibodies + assist in activation of T cells T cells - kill pathogens and regulate immunity

Answer 423

Large white blood cells that circulate in the blood They migrate into tissues and differentiate into macrophages

Answer 424

Engulf pathogens through phagocytosis

Answer 425

Fragmentation of megakaryocytes in the bone marrow

Answer 426

When a vessel is injured, platelets adhere and form a plug Clotting factors activate the coagulation cascade, leading to fibrin formation, which stabilises the clot and prevents blood loss

Answer 427

Friedrich Miescher (1869): Discovered a new molecule in the nucleus called nuclein (later known as DNA), rich in phosphorus Oswald Avery (1944): Showed that DNA, not protein, is the genetic material using bacterial transformation experiments Erwin Chargaff: * Found base pairing rules: [A]=[T], [G]=[C] * DNA composition varies between species Linus Pauling: Proposed an incorrect DNA model with bases on the outside Rosalind Franklin & Maurice Wilkins: Used X-ray diffraction to reveal DNA's helical structure James Watson & Francis Crick (1953): Proposed the double helix model of DNA (B-form), integrating Franklin's data and Chargaff’s rules.

Answer 428

A double-stranded right-handed helix, with an ionised sugar-phosphate backbone on the outside and bases on the inside

Answer 429

It is ionised, allowing favourable interactions with water, which contributes to DNA's solubility and structural stability

Answer 430

Each strand runs in opposite directions (one 5' to 3', the other 3' to 5'), allowing complementary base pairing

Answer 431

Hydrogen bonds between complementary base pairs: * A pairs with T (2 H-bonds) * G pairs with C (3 H-bonds)

Answer 432

DNA has a major groove and a minor groove Proteins typically bind at the major groove where more chemical information is exposed

Answer 433

a = H-bond acceptor, d = H-bond donor Minor Groove: * CG and GC = a/d/a * AT and TA = a/a Major Groove: * CG = d/a/a * GC = a/a/d * TA = hydrophobic/a/d/a * AT = a/d/a/hydrophobic

Answer 434

A phosphate group A pentose sugar (β-D-2’-deoxyribose) A nitrogenous base (Adenine, Guanine, Cytosine, Thymine)

Answer 435

Purines: * Adenine (A) + Guanine (G) * Two rings, bond via N9 Pyrimidines: * Cytosine (C) + Thymine (T) * One ring, bond via N1

Answer 436

Because purines (larger) always pair with pyrimidines (smaller), maintaining uniform spacing between the strands

Answer 437

π–π stacking (van der Waals interactions) between adjacent base pairs

Answer 438

The phosphodiester backbone has a pKa ~1, making DNA negatively charged at physiological pH This gives it water solubility and allows interaction with counter-ions like Na⁺, K⁺, Mg²⁺, spermine, and spermidine

Answer 439

Water forms a spine of hydration in the grooves and stabilises the DNA through hydrophilic interactions with the backbone

Answer 440

Supercoiling, which compacts the DNA and reduces strain during replication or transcription Looping and scaffolding within the chromosome Association with histone proteins forming nucleosomes and further folding into chromatin

Answer 441

Introns are non-coding regions of DNA (23% of human genome) Exons are coding regions of DNA (1.1% of human genome)

Answer 442

Role: store of information Structure: DNA's sequence of nitrogenous bases (A, T, C, G) encodes genetic instructions, Link: allowing it to function as a stable, long-term repository of information Role: replication mechanism Structure: The complementary base pairing (A with T, C with G) enables semi-conservative replication, where each strand serves as a template for a new one. Link: This ensures that genetic information is accurately copied and passed from one generation to the next during cell division and reproduction.

Answer 443

DNA * Deoxyribose sugar * Thymine nucleobase * Double stranded * Larger in size * More stable * Chargaff rule applies RNA * Ribose sugar * Uracil nucleobase (doesn't have a methyl group) * Single stranded * Smaller in size * Less stable * Chargaff rule does not apply

Answer 444

RNA is less stable than DNA Because of the hydroxyl group, under slightly basic conditions the phosphate can be attacked leading to cleavage of the backbone This is important because it means that RNA can be broken down easily allowing for gene expression to be regulated

Answer 445

Single-stranded polymer of nucleotides Can fold into various shapes (e.g. hairpins, loops, bulges, etc.), through regional/local complementary bases pairing, which facilitates its diverse functions in the cell

Answer 446

Two identical copies of the original DNA molecule is produced, each of which contains: one of the original strand and one newly synthesised strand Each newly formed DNA molecule consists of one original (parental) strand and one newly synthesised strand

Answer 447

Helicase unwinds the DNA helix by breaking hydrogen bonds between bases, forming a replication fork. Single-strand binding proteins prevent rejoining of strands. Topoisomerase relieves supercoiling by creating temporary cuts in DNA

Answer 448

E. coli was grown in heavy nitrogen (N-15) and then transferred to light nitrogen (N-14) DNA samples were centrifuged using a CsCl density gradient to separate DNA based on density Generation 0: * DNA formed a single heavy band (all N-15). Generation 1: * DNA formed a single intermediate band, showing hybrid DNA (N-15/N-14) * Ruling out conservative replication Generation 2: * Two bands appeared — one intermediate and one light * Supporting semi-conservative replication, where each new DNA molecule contains one old and one new strand.

Answer 449

Primase synthesises a short RNA primer (8–10 nucleotides) to provide a 3'-OH group for DNA polymerase. This is important because DNA polymerase cannot initiate synthesis without a primer as it can only add nucleotides to an existing strand

Answer 450

DNA polymerase extends from the primer, adding nucleotides in the 5’ → 3’ direction The leading strand is synthesised continuously toward the replication fork The lagging strand is synthesised in Okazaki fragments away from the fork, each needing a new primer DNA polymerase also proof-reads as it moves along by removing incorrectly matching nucleotides that are accidentally added

Answer 451

The RNA primers are removed by the enzyme exonuclease and the resultant gaps are filled with nucleotides by DNA polymerase I

Answer 452

DNA ligase joins the Okazaki fragments on the lagging strand, creating a continuous strand of DNA

Answer 453

1. Helicase unwinds the DNA helix by breaking hydrogen bonds between bases, forming a replication fork. 2. Single-strand binding proteins prevent the strands from rejoining of strands and topoisomerase relieves tensions by creating temporary cuts in DNA, preventing supercoiling 3. Primase synthesises a short RNA primer (8-10 nucleotides long), providing a starting point for DNA synthesis 4. DNA polymerase attaches to the primer and starts forming the new strands 5. One strand (leading strand) is continuous, in the same direction as the replication fork 6. The other strand (lagging strand) is made in small pieces (Okazaki fragments), requiring a new primer for each, moving away from the replication fork 7. Exonuclease removes RNA primers and the resultant gaps are filled by DNA polymerase I 8. DNA ligase joins the Okazaki fragments together 9. Once both strands are fully replicated, the replication process ends, resulting in two identical DNA molecules, each containing one old strand and one new strand

Answer 454

The synthesis of the leading and lagging strands is coordinated by the replisome, using the trombone model The lagging strand forms a loop, allowing its polymerase to stay near the leading strand polymerase This loop enables discontinuous synthesis of Okazaki fragments in the 5' → 3' direction The loop grows and releases with each fragment, maintaining synchronised replication of both strands at the replication fork

Answer 455

Topoisomerase activity is essential because it resolves the topological stress that arises during DNA replication and transcription. When helicase unwinds the DNA double helix, it creates tension in the DNA molecule. This tension leads to supercoiling (over-winding) ahead of the fork. Topoisomerases prevent this by creating temporary cuts and rejoining DNA strands to relieve supercoiling and untangle knots. However, topoisomerase activity can also be toxic. If a topoisomerase introduces breaks in the DNA but fails to reseal them due to malfunction or interference, it leaves behind persistent DNA breaks. These breaks can lead to genome instability, mutations, or cell death.

Answer 456

The enzyme DNA ligase can help prevent toxicity by resealing nicks and breaks left by topoisomerase activity, ensuring that transient DNA cleavage events do not become permanent

Answer 457

E.g. Gemcitabine, Mitomycine C Polymerase inhibitors block DNA polymerase, the enzyme responsible for synthesising new DNA strands. By doing so, they: * Prevent the addition of nucleotides to the growing DNA chain * Cause DNA damage or incomplete replication, triggering cell death

Answer 458

E.g. Cisplatin, Mitomycine C Large chemical groups that attach to DNA strands, preventing proper base pairing and blocking DNA polymerase progression

Answer 459

Polymerase Chain Reaction (PCR) is a laboratory technique used to amplify specific DNA sequences, making them easier to study Process: 1. Denaturation: The DNA template is heated to around 94-98°C, causing the double-stranded DNA to separate into two single strands. 2. Annealing: The reaction temperature is lowered to 50-65°C, allowing short DNA primers to bind to the complementary sequences on the single-stranded DNA. 3. Extension: DNA polymerase adds nucleotides to the primers, extending the DNA strand in the 5’ to 3’ direction, at around 75-80°C. 4. These steps are repeated for 20-40 cycles, resulting in the exponential amplification of the target DNA sequence.

Answer 460

Size Pattern of G-bands Location of centromere: * Metacentric = centromere in the middle, arms of equal length * Submetacentric = centromere slightly off-center * Acrocentric = centromere close to one end

Answer 461

The human karyotype is 46 chromosomes, including 22 pairs of autosomes and 1 pair of sex chromosomes

Answer 462

Sister chromatids: * Identical copies of a single chromosome, formed after DNA replication in the S phase * Held together at the centromere * Exact genetic replicas * Present only during and after DNA replication - separate during anaphase of mitosis or anaphase II of meiosis Homologous chromosomes: * A pair of chromosomes, one from each parent * Similar in size, shape and genetic content but not identical * Do not share a centromere * Separate during meiosis I * Present in diploid cells

Answer 463

The specific physical location or position of a gene on a chromosome Each gene is located at a specific locus on a chromosome, which is consistent across individuals of the same species E.g. the gene for eye colour in humans is located at a particular locus on chromosome 15

Answer 464

Every inherited characteristic/trait is defined by a gene pair Due to the meiosis process, each offspring receives one allele from each parent to make a gene pair

Answer 465

Genes for different traits are sorted separately from one another so that the inheritance of one trait is not dependent on the inheritance of another

Answer 466

An organism with alternate forms of a gene will express the form that is dominant. (One gene is dominant and one is recessive)

Answer 467

Monogenic disorders are caused by a mutation in a single gene (E.g. Cystic fibrosis, Sickle cell anaemia, Huntington's disease) Polygenic disorders are caused by multiple gene mutations and environmental factors (E.g. Type II diabetes, Rheumatoid arthritis, Schizophrenia)

Answer 468

Autosomal recessive Autosomal dominant X-linked recessive X-linked dominant Mitochondrial

Answer 469

Both copies of the gene (one from each parent) must be mutated for the disorder to occur If an individual inherits only one mutated allele, they are a carrier and typically do not show symptoms Affects males and females equally E.g. Cystic Fibrosis, Sickle Cell Anaemia

Answer 470

Only one copy of the mutated gene, inherited from either parent, is sufficient to cause the disorder Affects males and females equally E.g. Huntington's disease

Answer 471

The mutated gene is located on the X chromosome Two copies of the mutated gene (one on each X chromosome) are needed for females to express the disorder Males, having only one X chromosome, will express the disorder if they inherit the mutated gene Affected fathers cannot pass the disorder to their sons but will pass it to daughters E.g. Hemophilia A and B, Red-green color blindness

Answer 472

The mutated gene is located on the X chromosome, and only one copy of the mutated gene is needed to cause the disorder Affects males and females equally

Answer 473

Passed exclusively from mothers to their offspring, as only the egg contributes mitochondria to the zygote Affects males and females equally

Answer 474

Twin Studies Compare the concordance rates (likelihood of both individuals having the disorder) between identical twins (monozygotic - sharing 100% of their DNA) and fraternal twins (dizygotic - sharing 50% of their DNA) If identical twins have a much higher concordance rate than fraternal twins, the disorder is likely to have a strong genetic component If concordance rates are similar, environmental factors may play a larger role

Answer 475

If a generation is skipped (i.e. unaffected parents have affected offspring), dominant inheritance is unlikely → likely recessive If male offspring do not inherit the condition from an affected mother, the condition is unlikely to be X-linked Autosomal dominant traits typically appear in every generation Consistent transmission from fathers to sons suggests autosomal, not X-linked inheritance

Answer 476

Malaria is caused by a parasite which infects the red blood cells. Individuals who carry the mutated β-globin gene are protected against malaria because the parasite is less able to survive and reproduce in sickle-shaped red blood cells