DNA Structure and Replication

DNA is literally the instruction manual for life, stored as a double helix - imagine a twisted ladder where the rungs are made of complementary base pairs. Each strand consists of nucleotides containing deoxyribose sugar, phosphate, and bases (A, T, C, G), forming the iconic sugar-phosphate backbone.

The magic happens in base pairing: adenine always pairs with thymine $A-T$ and cytosine with guanine $C-G$, held together by hydrogen bonds. The two strands run in opposite directions (antiparallel), with specific 3' and 5' ends that matter hugely for replication.

When DNA copies itself, it unwinds into separate strands and DNA polymerase gets to work. Here's the catch - it only adds nucleotides in one direction (to the 3' end), so one strand copies smoothly whilst the other forms fragments that ligase must join together.

Key Insight: Think of DNA replication like unzipping a jacket - one side comes off easily, but the other needs to be done in sections!

Gene Expression in Eukaryotes

Your genes don't just sit there - they're constantly being read and converted into proteins through gene expression. First, RNA polymerase unzips the DNA double helix, breaking those hydrogen bonds between base pairs like opening a book.

The enzyme then creates a primary transcript by matching RNA nucleotides to the DNA template (remember: A pairs with U in RNA, not T). But here's where it gets interesting - this primary transcript contains both exons (coding regions) and introns $non-coding regions$.

During translation, the processed mRNA travels to ribosomes where tRNA molecules do the heavy lifting. Each tRNA carries a specific amino acid and has an anticodon that matches codons on mRNA. As tRNA molecules line up, peptide bonds form between amino acids, creating proteins.

The process starts and stops with specific start and stop codons - think of them as molecular punctuation marks that tell the ribosome where to begin and end protein synthesis.

Remember: Gene expression is like following a recipe - first you read it (transcription), then you cook it (translation)!

RNA Structure and Functions

Unlike DNA's double helix, RNA is a single strand of nucleotides, each containing ribose sugar, phosphate, and bases (A, C, G, and U instead of T). This simpler structure allows RNA to be incredibly versatile in the cell.

Three types of RNA work together like a well-coordinated team. mRNA carries the genetic code from nucleus to ribosome - it's essentially a mobile photocopy of your DNA instructions. tRNA acts as a translator, picking up specific amino acids and carrying them to ribosomes using its anticodon to match mRNA codons.

rRNA combines with proteins to form ribosomes themselves - the protein-making factories of your cells. Think of ribosomes as 3D printers that read mRNA instructions and assemble amino acids in the correct order.

The beauty of this system is that every three bases (codon) on mRNA codes for one amino acid, creating a universal genetic language that works across all life forms.

Fun Fact: You have about 37 trillion cells, and most are constantly making proteins using this RNA system right now!

RNA Splicing

RNA splicing is like editing a rough draft - your cells remove the unnecessary bits and keep only what's needed. After primary transcripts are made, cells must remove introns $non-coding regions$ and join together exons (coding regions) to create mature, functional mRNA.

This process isn't just simple cutting and pasting. Alternative splicing allows cells to create different versions of the same protein by keeping different combinations of exons. It's like having one recipe but being able to make several different dishes by including or excluding certain ingredients.

The order of exons always stays the same, but which exons are retained can vary, leading to different mature transcripts. This clever system explains how humans can make over 100,000 different proteins from only about 20,000 genes.

Why This Matters: Alternative splicing means one gene can code for multiple proteins - it's biological efficiency at its finest!

Stem Cells and Differentiation

Stem cells are your body's ultimate multitaskers - unspecialised cells that can transform into any type of cell your body needs. Think of them as biological Swiss Army knives, ready to become whatever's required.

Embryonic stem cells are the most versatile, capable of differentiating into all cell types in your body. Adult stem cells are more limited but still crucial - they replace damaged cells in specific tissues throughout your life. Once cells differentiate, there's no going back; they've committed to their specialised role.

The magic happens through selective gene expression - differentiated cells only "switch on" genes needed for their specific function. A heart muscle cell expresses completely different genes than a brain cell, even though they contain identical DNA.

Stem cell research offers incredible therapeutic potential for treating diseases like diabetes, Parkinson's, and leukaemia. However, it raises ethical questions, particularly around embryonic stem cell use, leading to strict regulations and alternative approaches like induced pluripotent stem cells.

Looking Forward: Stem cell therapy could revolutionise medicine by allowing us to grow replacement tissues and organs!

Enzyme Action and Inhibition

Enzymes are biological catalysts that speed up reactions by lowering activation energy - think of them as molecular matchmakers that bring reactants together perfectly. The active site doesn't just fit substrates like a rigid lock and key; it actually changes shape through induced fit to optimise the reaction.

This flexibility is crucial because it orientates reactants correctly and reduces the energy needed for reactions to occur. Once products form, they have low affinity for the active site and quickly leave, allowing the enzyme to work again.

Competitive inhibition occurs when molecules that resemble the substrate compete for the active site - imagine someone trying to use the wrong key in a lock. You can overcome this by adding more substrate to outcompete the inhibitor.

Non-competitive inhibition works differently - inhibitors bind elsewhere and change the active site shape, reducing the enzyme's effectiveness. Product inhibition provides clever feedback control, preventing cells from making too much of any substance.

Real-World Connection: Many medicines work as enzyme inhibitors - aspirin inhibits enzymes involved in inflammation!

Glycolysis and Citric Acid Cycle

Glycolysis breaks down glucose into pyruvate, but it's not immediately profitable - cells must invest 2 ATP molecules to phosphorylate intermediates during the energy investment phase. Think of it like spending money to make money.

The pay-off stage produces 4 ATP, giving a net gain of 2 ATP per glucose molecule. When oxygen is available, pyruvate enters the citric acid cycle (also called Krebs cycle) where the real energy harvest begins.

Pyruvate converts to an acetyl group, which combines with coenzyme A to form acetyl-CoA. This then combines with oxaloacetate to form citrate, starting the cycle. The cycle is controlled by dehydrogenase enzymes that remove high-energy electrons and hydrogen ions.

Throughout the cycle, ATP is generated, CO₂ is released, and oxaloacetate is regenerated to keep the cycle spinning. Most importantly, NAD captures high-energy electrons that will power the next stage of cellular respiration.

Energy Perspective: Glycolysis and the citric acid cycle are like mining operations - extracting energy stored in glucose bonds!

Skeletal Muscle Metabolism and Fibre Types

When you exercise intensely, your muscles can't get enough oxygen for normal respiration, so they switch to lactic acid metabolism. Pyruvate converts to lactic acid, transferring hydrogen from NADH and regenerating NAD needed for glycolysis to continue producing ATP.

Lactic acid build-up causes muscle fatigue and creates an oxygen debt. After exercise stops, your liver converts lactic acid back to pyruvate or glucose - that's why you keep breathing heavily after intense exercise.

Slow-twitch muscle fibres are built for endurance - they contract slowly but maintain contractions for ages. They're packed with mitochondria, have rich blood supply, and high myoglobin concentrations for oxygen storage. Fats are their preferred fuel for long-distance activities like marathon running.

Fast-twitch fibres are sprint specialists - they contract quickly but fatigue rapidly. They have few mitochondria, poor blood supply, and rely on glycolysis for ATP. Their fuel sources are glycogen and creatine phosphate for explosive activities like weightlifting or sprinting.

Training Tip: You can't change your muscle fibre ratios, but you can train both types to perform better in their specialised roles!

NADH Production and Electron Transport Chain

The electron transport chain is where cellular respiration reaches its spectacular finale. Dehydrogenase enzymes remove hydrogen ions and high-energy electrons during glycolysis and the citric acid cycle, passing them to NAD and FAD carriers.

NADH and FADH₂ deliver these electrons to the electron transport chain - a series of carrier proteins embedded in the mitochondrial membrane. As electrons pass along the chain, energy is released and used to pump hydrogen ions across the membrane, creating a concentration gradient.

The return flow of hydrogen ions through ATP synthase drives ATP production - imagine water flowing through a turbine to generate electricity. This process produces far more ATP than glycolysis alone.

Oxygen acts as the final hydrogen acceptor, combining with hydrogen to form water - which is why you need to breathe during cellular respiration. Without oxygen, the entire electron transport chain grinds to a halt.

Energy Facts: The electron transport chain produces about 32-34 ATP molecules per glucose - that's massive efficiency compared to glycolysis!

PCR and Personalised Medicine

PCR (Polymerase Chain Reaction) is molecular photocopying that amplifies specific DNA sequences millions of times. The process uses three temperature stages: heating to 90-98°C separates DNA strands, cooling to 50-65°C allows primers to bind, and heating to 70-80°C lets DNA polymerase extend new strands.

Primers are crucial - they're complementary sequences that mark exactly where amplification should start. Heat-resistant Taq polymerase survives the high temperatures, and repeated cycles exponentially increase DNA copies. This technique revolutionised forensics, paternity testing, and medical diagnostics.

Personal genomics involves analysing your individual genome to understand your unique genetic makeup. Genomics studies entire genomes, revealing how genetic variations affect disease susceptibility and treatment responses.

This leads to personalised medicine - treatments tailored specifically to your genetic profile. Pharmacogenetics uses genomic information to determine optimal drug choices and dosages, potentially eliminating trial-and-error prescribing and reducing adverse reactions.

Future Medicine: Soon, your genetic profile could determine everything from cancer treatments to preventive care strategies!