Untitled Quiz

Biochemistry

• Amino acids: There are 20 natural amino acids.
• Each has a primary amino group, carboxyl group, H atom, and a R group (central α-carbon).
• Proline has a secondary amine group.
• Enantiomers: All amino acids except glycine have a chiral center.
• Only L isomers are found in proteins.
• D-amino acids are found in bacterial cell walls and certain antibiotics.
• Different R groups (side chains) lead to different physiochemical properties.
• Glycine has an H atom as its R group.
• Alanine, valine, leucine, isoleucine, and methionine have aliphatic side chains (hydrophobic + inert).
• Phenylalanine, tyrosine, and tryptophan have aromatic side chains (hydrophobic).
• Proline has an aliphatic side chain bonded to its amine group, making it an imino acid.
• Cysteine has a sulfur-containing side chain.
• Arginine and lysine have +vely charged side chains.
• Histidine has a basic side chain.
• Aspartic acid and glutamic acid have acidic side chains.
• Asparagine, glutamine, serine, and threonine are uncharged but polar; they can form hydrogen bonds.

Protein Structure

• Proteins are sequences of amino acids linked by peptide bonds.
• A peptide bond is a covalent bond between the α-amino group of one amino acid and the α-carboxyl group of another.
• Chains of <25 amino acids are called oligopeptides; >25 amino acids are polypeptides.
• Two linked amino acids are called a dipeptide.
• A condensation reaction forms peptide bonds.
• Proteins have different levels of structure (primary, secondary, tertiary, and quaternary).
• Primary structure is the linear sequence of amino acids.
• Secondary structure includes α-helices and β-pleated sheets.
• Tertiary structure is the three-dimensional arrangement of the amino acid chain.
• Quaternary structure describes the arrangement of multiple polypeptide chains.

Enzymes

• Enzymes are catalysts that speed up chemical reactions without being changed themselves.
• They are highly stereo-specific, meaning they only react with certain stereoisomers of a molecule.
• The active site is the region of an enzyme that binds to the substrate and converts it to a product.
• The substrate binds to the active site by weak forces, forming an ES complex.
• Substrate specificity is determined by the properties and spatial arrangement of the amino acid residues forming the active site.
• Enzymes are classified into six main groups based on the type of reaction they catalyze.
• Each enzyme has a unique 4-digit classification number.
• Enzyme assays measure the rate of conversion of a substrate to a product under various conditions.
• Coenzymes transfer groups from one molecule to another(some enzymes need to be able to function).
• Prosthetic groups are non-protein components that are essential to some enzymes’ function.
• Isoenzymes are different forms of an enzyme that catalyze the same reaction but have different physical or kinetic properties.

Thermodynamics

• Gibbs free energy is the energy available to do useful work in a system at constant temperature and pressure.
• If Gibbs free energy is negative, the reaction can occur spontaneously.
• If Gibbs free energy is positive, the reaction requires an input of energy to occur.
• Activation energy is the minimum energy required to initiate a chemical reaction.
• Enzymes lower the activation energy, making reactions occur more quickly.

Enzyme Kinetics

• Enzyme activity is the initial rate at which an enzyme catalyzes a reaction, expressed by its start.
• Low substrate concentration = low reaction rate (fewer collisions with an enzyme).
• Doubling substrate concentration = doubles the reaction rate (proportional).
• Too much substrate, reaction rate plateaus because the enzyme is saturated; reaction rate then depends on how fast the product can dissociate from the enzyme.
• Ideal substrate concentration= the rate is dependent on how fast the product can dissociate from the enzyme.
• Increasing enzyme concentration while maintaining substrate concentration =doubles the reaction rate.
• Temperature: Higher temperatures increase enzyme activity as substrate molecules have sufficient energy to overcome activation energy required to collide with an enzyme = > reaction rate.
• However, very high temperatures denature the enzyme's 3D tertiary structure = < reaction rate.
• pH: Optimal pH is when amino acid functional groups ionize correctly = maintains protein structure's proper conformation, denaturing can occur outside that range = < reaction rate.

Michaelis-Menten Model

• An enzyme (E) combines with a substrate (S) to form an enzyme-substrate complex (ES).
• The complex then releases products (P) and the free enzyme (E).
• Km is the Michaelis constant, a measure of an enzyme's affinity for its substrate.
• A low Km value means a high affinity, and a high Km value means a low affinity for the substrate.
• Vmax is the maximum velocity of an enzyme-catalyzed reaction, which occurs when the enzyme is saturated with substrate.
• Lineweaver-Burk plots are used to graphically determine Km and Vmax values.

Enzyme Inhibition

• Enzyme inhibitors reduce the activity of enzymes.
• Irreversible inhibitors bind permanently to an enzyme, often forming covalent bonds.
• Reversible inhibitors can bind and unbind and include competitive inhibitors.
• Competitive inhibitors structurally resemble substrates, competing for the active site.
• Noncompetitive inhibitors bind to a site away from the active site, causing a conformational change that reduces enzymatic activity.

Cells

• Cells are the basic units of life.
• Organelles are specialized structures within cells with specific functions.
• Cell membranes regulate materials entering and exiting the cell.
• The cytoplasm contains all cellular components, excluding the nucleus.
• The cytosol is the liquid portion of the cytoplasm. The nucleus regulates DNA and RNA actions; it is surrounded by a double-layered membrane.
• The nucleus contains nucleoli.
• DNA, organized into chromatin or chromosomes, controls protein synthesis.

Endoplasmic Reticulum

Highly convoluted single membrane-enclosed compartment = netlike meshwork/tube-like channels. Rough ER: Has ribosomes on outer membrane -> protein synthesis + transport. Smooth ER: No ribosomes -> lipid synthesis + transport, detoxification of drugs.

Ribosomes

• Site of protein synthesis Consist of RNA + protein
• Function is to transcribe and translate genetic information for protein synthesis.

Vacuoles/Vesicles

• Membrane bound organelles involved in storage for water, nutrients, and waste products.

Lysosomes

• Membrane-bound organelles containing digestive enzymes involved in breaking down waste products, pathogens, and worn-out organelles.

Golgi Apparatus

• Structure: 4-6 flattened, smooth membrane-bound compartments associated with vesicles.
• Function: Protein packaging, modification, and transportation.

Mitochondria

• Oxidative phosphorylation, site of ATP production from food energy.
• Has a double membrane -> inner membrane folded into cristae -> matrix inside.

DNA Replication and Protein Synthesis

• DNA replication is the process where DNA produces a copy of itself.
• Protein synthesis involves converting information from DNA into proteins.
• Stages of conversion of chemical food energy to ATP.
• Mitochondrial diseases arise from mutations in the mitochondrial DNA.
• Protein synthesis includes Transcription and Translation.
• Transcription is creating mRNA from the DNA template.
• Translation is reading the mRNA and creating the amino acid chain (protein).

Cytoskeleton and Centrioles

• Cytoskeleton: Provides structure and support to cells, includes actin filaments (shape change) and microtubules.
• Centrioles: microtubules involved in cell division.

Cell Membranes

• Composed of phospholipid bilayer, proteins, cholesterol.
• Proteins include channels (facilitated diffusion), pumps (active transport), and receptors.
• Vesiculation is the process in which materials move in and out of a cell (including endocytosis and exocytosis).

Facilitated Diffusion and Active Transport

• Facilitated diffusion transports substances across a membrane via protein channels that are faster than simple diffusion.
• Active transport uses carrier proteins coupled to an energy source to move substances against their concentration gradient.

DNA Composition and Structure

• Consists of nucleotides (phosphate group, pentose sugar, nitrogenous base).
• Nitrogenous bases in DNA include adenine, thymine, cytosine, and guanine (A-T, G-C pairings).
• Purines (A and G) consist of two fused rings, while pyrimidines (C and T) consist of one ring.
• DNA strands are held together by hydrogen bonds between complementary bases and forms a double helix.

DNA Replication/Mitosis

• Two DNA strands are separated using enzymes (template for new strands).
• These enzymes bring correct nucleotides to existing bases, creating two new DNA double helices (each with one strand from the original strand and one new strand.)
• DNA condenses around histone proteins and forms chromosomes.

Cancer

• Uncontrolled cell division.
• Lifestyle factors and genetics.
• Local disease- restricted to the tissue of origin.
• Metastasis- cancer cells invade and colonize other cell territories (harder to treat).
• Hallmarks: self-sufficiency in growth signals, insensitivity to anti-growth signals, limitless replicative potential, evading apoptosis, sustained angiogenesis, tissue invasion and metastasis.
• Causation- Smoking, body weight, physical activity levels, diet (processed/red meat), alcohol, hormones, UV, genetics, environment.
• Cancer treatments include Surgery, Radiotherapy, Chemotherapy, Targeted therapy.

How Obesity can Increase Cancer Risk

• Fat cells can produce more oestrogen-> affecting tissue growth, increasing the risk of certain cancers.
• Increased levels of insulin and other growth factors can prompt cells to divide more rapidly, which also increases the risk of cancer.

Protein synthesis lecture

• Central dogma = DNA to RNA to Protein
• Proteins composed of Amino Acids.
• 20 AA
• Transcription: DNA to mRNA.
• DNA is too large to leave the nucleus.
• mRNA leaves nucleus to act as a template in the cytoplasm.
• mRNA binds to Ribosomes in the cytoplasm.
• Translation: mRNA to polypeptide.
• Decoding of the mRNA message into polypeptide chain.
• tRNA brings anticodons that are complimentary to the codon on the mRNA and specific attached AA.

tRNA structure

• Amino acid binds to tRNA; anticodons sequence are complementary to the mRNA codon; allow tRNA to bring the correct amino acid to the mRNA.
• Translation: small and large subunit complexes with initiation factors form base pairs with the start codon sequence of the mRNA.
• Start codon (AUG) on the mRNA is positioned in the P site on the ribosome.
• Formyl-methionyl tRNA joins (1st AA)
• Large subunit on the ribosome joins = GTP hydrolyses to GDP+Pi, initiation factors leave the ribosome.

Elongation of translation

• Three binding sites (APE) - usually only two are occupied at a time.
• Aminoacyl acceptor site(A) - aminoacyl-tRNA enters
• Peptidyl site (P) - bonds form between AA's-holds tRNA
• Exit site(E) - tRNA exits
• EFTU catalyzes delivery of AA-tRNA to ribosome.
• EFG catalyses hydrolysis of GTP -> GDP + Pi -> conformational change in EFG.
• Peptide bond forms between AA at A and P sites -> ribosome moves 1 codon forwards = tRNA moves from A site to P site, amino acid on mRNA.
• Unloaded tRNA moves to the E site.
• Process repeats until stop codon reached.

Termination of translation

• Special release factors bind to the A site - stop codon reached.
• Polypeptide in the P site is hydrolysed from tRNA and exits the exit tunnel.
• Ribosomal subunits dissociate = ready to be reused.

Antibiotics and Ribosomes

• Antibiotics target bacterial ribosomes and disrupt their function.
• Streptomycin inhibits initiation.
• Linezolid prevents large subunit binding.
• Tetracycline prevents aminoacyl-tRNA binding to the A site.
• Chloramphenicol inhibits peptide bond formation.
• Erythromycin blocks the exit tunnel.
• Aminoglycosides inhibit initiation, and are extremely effective but toxic.
• Macrolides -> block exit channel on ribosome
• Mutations in rRNA or ribosomal proteins can cause antibiotic resistance.

Genome-Less Complex Than Proteome

• A single gene can lead to multiple RNA transcripts that produce multiple versions of a single protein.
• Post-translational modifications (PTMs) modify amino acids after translation, altering protein structure and function.
• Important for cellular activity regulation (e.g., phosphorylation).
• Kinases and phosphatases are important enzymes that activate or deactivate proteins.
• Crucial for understanding cellular processes, disease, and drug action.

Drugs and Central Dogma

• Drugs can bind to DNA directly (via covalent adducts or intercalating agents) to inhibit DNA replication, transcription, and reverse transcription.
• This affects translation and protein synthesis.

Cancer Lecture 1

• Uncontrolled cell division.
• Lifestyle factors and genetics are major influences.
• Local disease- restricted to the tissue of origin,
• Metastasis- cancer cells invade and colonise other Territories (harder to treat).
• Hallmarks of cancer: self-sufficiency in growth signals, insensitivity to anti-growth signals, limitless replicative potential, evading apoptosis, sustained angiogenesis, tissue invasion and metastasis.
• Causation: smoking, body weight, physical activity levels, diet (processed/red meat), alcohol, hormones, UV, genetics, environment.

Lecture Cancer 3

• Cancer treatments include surgery, radiotherapy, chemotherapy and targeted therapy.
• Surgery may not always be possible, depending on the location and extent of the cancer.
• Radiotherapy depends on the location, and limits toxicity to surrounding tissues.
• Chemotherapy targets rapidly growing cells and works in three main stages: binding to DNA, preventing DNA replication and inhibiting components of cell division.
• Personalized therapy can help predict patients' ability to metabolize and experience adverse effects of treatment, and it uses prognostic markers.
• Targeted therapy interferes with specific molecular pathways involved in cancer growth.

Unexplained/Persistent/Unusual Changes

• Unexplained changes - lumps, swellings, persistent coughs, voice changes, breathing problems.
• Persistent changes - sores that don't heal, digestive problems, unusual bleeding.
• Unusual changes- moles, skin changes, changes in breast size, shape or nipple.
• Weight loss
• Pain that persists.
• Important to consult a doctor if experiencing these changes, especially if they persist for several weeks.
• Tips for checking potential cancer risk factors, including family history, lifestyle, age, ethnicity.

Secondary Protein Structure Lecture

• Polypeptide folding is not random.
• Some conformations are more suitable/favourable due to the structure and rigidity of peptide bonds.
• Secondary structures (alpha helices and beta strands) exist due to hydrogen bonding between peptide bonds.
• Phi and psi angles control protein folding.
• Alpha-helix: A right-handed coil, stabilized by hydrogen bonds between amino acids located four residues apart.
• Beta-sheets: A pleated sheet, stabilized by hydrogen bonds between segments of polypeptide chain running side-by-side.

Tertiary Protein Structure Lecture

• Loops and bends control protein size and shape, and connect other secondary structures.
• Hydrophobic bonding = interactions between hydrophobic amino acids and water.
• Polar/charged interactions are important forces between positively and negatively charged amino acids or polar amino acids in water.
• Important forces in stabilizing tertiary structures, include hydrogen bonds, ionic bonds and disulfide bonds.

Quaternary Protein Structure Lecture

• Haemoglobin is a protein composed of 4 polypeptide chains(2 alpha and 2 beta)
• When O2 binds to hemoglobin, it causes a conformational change in the molecule, allowing for cooperative binding - cooperative binding is where the binding of one ligand increases the affinity for other ligands.
• Movement of corners (of structure).
• Each subunit has a heme group - the heme group contains an iron atom that binds to oxygen.

Allostericity and 2,3 Biphosphoglyceric Acid

• Allosteric regulation describes the change in an enzyme or proteins activity when a molecule (the allosteric effector) binds to a site away from the active site.
• 2,3-biphosphoglyceric acid (BPG) binds to the central cavity of hemoglobin subunits, stabilizing the T-state. BPG binds better to deoxygenated hemoglobin, and reduces hemoglobin affinity.

Enzymes Lecture

• Enzymes are proteins that catalyze biochemical reactions.
• Enzymes have specific properties like rate acceleration, active site, and chirality.
• They require coenzymes for catalytic function (some need metal ions, some are complex organic molecules)
• 6 different classes of enzymes- oxidoreductases, transferases, hydrolases, lyases, isomerases, ligases
• Enzymes have specific mechanisms to speed up chemical reactions, these mechanisms are discussed in enzyme kinetics and dynamics.

Drugs and Diseases

• Aspirin inhibits cyclooxygenase (COX) enzyme, which is involved in prostaglandin synthesis (related to pain reduction and fever).
• Methotrexate inhibits dihydrofolate reductase (DHFR) enzyme critical in nucleotide synthesis.

Pharmacogenomics Lecture

• Pharmacogenomics studies how genetic variations influence a patient response to medicine, which impacts drug efficacy and toxicity.
• Genetic variations like deletions, copy number variants, chromosomal rearrangements, and single nucleotide polymorphisms cause differences in the body's metabolism or response to drugs.
• This lecture explores how different types of genetic variation affects drug metabolism and causes differences in patient's responses (efficacy and toxicity).
• Pharmacogenomics is important as it helps predict patient responses to drugs based on their genetic makeup, which can improve drug efficacy and reduce adverse effects.

Interactions Between Molecules Lecture

• Wallace's rule predicts the temperature at which DNA strands separate based on the base pair content.
• Packing interactions, including pi-pi stacking, influence the way molecules arrange themselves.
• Penicillin mechanism of action: binds with the residue to prevent bacterial cell wall synthesis.
• Oregano-phosphates are implicated in nerve impulse communication and affect acetylcholinesterase enzyme activity.

Health and Disease Concepts

• Health encompasses complete mental, physical, and social well-being.
• Disease involves a disturbance in body function due to some pathology or abnormality.
• Illness is the individual's experience (or perception) of being unwell.
• Health is measured by mortality, morbidity, life expectancy, and quality-adjusted life years.
• Society deals with illness using social norms and approaches to deviance.