The Proteome

Your genome contains about 20,000-25,000 genes, but here's the mind-blowing bit - your proteome (all the proteins your body can make) contains between 250,000 and 1 million different proteins! This massive difference happens because of RNA splicing and post-translational modifications.

Think of it like having a basic recipe book (genome) but being able to create hundreds of variations of each dish through different cooking techniques. One gene can code for multiple proteins through various modifications after the initial protein is made.

Not every gene gets expressed as a protein in every cell type. The proteins a cell makes depend on factors like metabolic activity, cellular stress, response to signalling molecules, and whether the cell is healthy or diseased. This flexibility allows your muscle cells to be completely different from your brain cells, even though they share the same DNA.

Key Point: Your proteome is dynamic - it changes based on what your cells need at any given moment, making it far more complex than your static genome.

Intracellular Membranes

Eukaryotic cells face a serious problem - they're massive compared to bacterial cells, which gives them a rubbish surface area to volume ratio. The plasma membrane alone simply isn't big enough to handle all the jobs these complex cells need to do.

The solution is brilliant: internal membrane systems. Your cells are packed with folded membranes that dramatically increase the available surface area for vital processes like protein production and energy generation.

The endoplasmic reticulum (ER) forms a network of membrane tubes connected to your nucleus, working as a manufacturing and packaging system. The Golgi apparatus consists of stacked membrane discs that modify and sort proteins. Lysosomes are membrane-bound sacs filled with digestive enzymes, whilst vesicles act like delivery trucks, moving materials between different membrane compartments.

Remember: Think of internal membranes as your cell's factory floor - without enough workspace, nothing would get done efficiently!

Synthesis of Membrane Components

Your cells constantly need new membrane components - both lipids and proteins - to maintain and expand their internal systems. The ER is your cell's membrane factory, handling production of both these essential components.

Lipid synthesis happens when enzymes in the ER membrane collect components floating in the cytosol and build phospholipids. These are immediately inserted into the ER membrane, causing it to grow. Sections can then be packaged into vesicles and shipped to other membrane systems.

Protein synthesis is more complex. All proteins start being made on ribosomes in the cytosol, but those destined for membranes or secretion need special treatment. They contain a signal sequence - a short stretch of amino acids that acts like a postal code, directing the ribosome to dock with the rough ER (called "rough" because it's covered in ribosomes).

Top Tip: The signal sequence is like your protein's address label - without it, the protein would end up in the wrong place and couldn't do its job properly.

Movement and Secretion of Proteins

Once proteins are made in the rough ER, they need to travel to the Golgi apparatus for their final modifications before reaching their destinations. This journey happens via vesicles - tiny membrane bubbles that bud off from the ER and fuse with the Golgi.

The Golgi apparatus works like a post office and modification centre combined. As proteins move through the stacked discs, enzymes add carbohydrates and make other post-translational modifications. Secretory vesicles then transport finished proteins along microtubules (cellular highways) to the plasma membrane or other destinations.

Post-translational modification is crucial for protein function. Beyond adding chemical groups like carbohydrates, many proteins undergo proteolytic cleavage - having bits chopped off to activate them. Digestive enzymes are perfect examples - they're made in inactive forms to prevent them damaging the cells that produce them, then activated only when needed.

This system ensures proteins are properly modified, correctly targeted, and safely transported without causing cellular damage.

Real-World Connection: Digestive enzymes being inactive until needed is like keeping powerful tools locked away until you actually need to use them - safety first!

Amino Acids and Protein Structure

Proteins are built from about 20 different amino acids linked by strong peptide bonds. Each amino acid has a unique R group that determines its properties - some are hydrophobic $water-hating$, others hydrophilic $water-loving$, and some carry electrical charges.

Protein structure has four levels of organisation. Primary structure is simply the sequence of amino acids. Secondary structure forms when the protein backbone folds into alpha helices, beta sheets, or turns through hydrogen bonding.

Tertiary structure is the final 3D shape, stabilised by interactions between R groups including hydrophobic interactions, ionic bonds, hydrogen bonds, and disulfide bridges. Some proteins have quaternary structure - multiple protein subunits working together, like haemoglobin's four subunits.

Prosthetic groups are non-protein components that give proteins special abilities. The iron centre in haemoglobin carries oxygen, whilst the magnesium centre in chlorophyll captures light energy. Temperature and pH changes can denature proteins by disrupting these carefully balanced interactions.

Memory Hook: Think of protein folding like origami - the final shape depends on precise folds and interactions, and rough handling $heat/wrong pH$ ruins the structure.

Ligand Binding and Allosteric Regulation

Ligands are substances that bind to proteins, causing conformational changes that alter protein function. The binding site must have complementary shape and chemistry to the ligand - like a key fitting a lock.

Allosteric enzymes are particularly clever - they have active sites for their substrate plus separate allosteric sites for regulatory molecules called modulators. Negative modulators reduce the enzyme's activity, whilst positive modulators increase it. This allows precise control of enzyme activity.

Cooperativity occurs in proteins with multiple subunits, where binding at one site affects the others. Haemoglobin shows this perfectly - binding one oxygen molecule increases the affinity of the remaining three binding sites. This creates the characteristic sigmoid oxygen dissociation curve.

Environmental factors also matter. During exercise, increased temperature and CO₂ production (which lowers pH) reduce haemoglobin's oxygen affinity, causing more oxygen release to hardworking tissues. This is exactly when and where your body needs it most.

Exam Tip: Remember that allosteric regulation is like having multiple control switches on one machine - you can fine-tune performance based on different signals.

Reversible Phosphorylation

Phosphorylation - adding phosphate groups to proteins - is one of the most important post-translational modifications. Since phosphate groups are negatively charged, they disrupt existing ionic interactions and create new ones, causing conformational changes that can turn proteins on or off.

Protein kinases are enzymes that transfer the terminal phosphate from ATP to specific R groups on target proteins. This phosphorylation often activates proteins by changing their shape. Many crucial cellular processes, including cell division and metabolism, are controlled this way.

Protein phosphatases do the reverse job - they remove phosphate groups from proteins and transfer them to ADP, regenerating ATP. This creates a reversible on/off switch that cells use to rapidly respond to changing conditions.

When this phosphorylation system goes wrong, it can lead to abnormal cell behaviour and potentially cancer. Many cancer treatments target faulty kinases that cause cells to divide uncontrollably.

Clinical Connection: Understanding phosphorylation is crucial for developing cancer drugs - many target specific kinases that have gone rogue in cancer cells.

Membrane Proteins and Transport

The plasma membrane is a fluid mosaic of proteins embedded in a phospholipid bilayer. Phospholipids naturally form this bilayer because they have hydrophilic heads $water-loving$ and hydrophobic tails $water-repelling$.

Membrane proteins come in two main types. Integral proteins have hydrophobic R groups that interact strongly with the lipid bilayer, with some spanning the entire membrane (transmembrane proteins). Peripheral proteins sit on the surface, forming hydrogen bonds and ionic bonds with the aqueous environment.

The phospholipid bilayer blocks most molecules, but small hydrophobic molecules like oxygen and carbon dioxide can slip through by simple diffusion. Everything else needs help from transport proteins.

Channel proteins form water-filled pores and only allow passive transport. Examples include aquaporins (water channels), ligand-gated ion channels (opened by signal molecules), and voltage-gated ion channels (opened by electrical changes). Transporter proteins bind molecules and change shape to move them across, either passively or using energy for active transport.

Health Link: Cystic fibrosis results from faulty CFTR chloride channels, showing how crucial proper membrane transport is for health.

Specific Transport Mechanisms

Aquaporins are brilliant examples of ungated channels. Each subunit has six membrane-spanning domains forming alpha helices that create a narrow water pore. The pore is too small for hydrated ions to pass through, making it perfectly selective for water molecules.

Ligand-gated ion channels open when signal molecules bind, causing conformational changes. You'll find these at neuromuscular junctions and synaptic junctions between nerve cells, where they enable rapid communication.

Voltage-gated channels respond to changes in membrane potential and are critical for the rapid responses of neuronal and muscle tissue. They allow cells to generate and propagate electrical signals.

Active transport uses pump proteins like ATPases that directly break down ATP to power transport against concentration gradients. The sodium-potassium pump is the most important example in human cells, using massive amounts of energy to maintain vital ion gradients.

Disease Example: Cystic fibrosis shows what happens when chloride transport goes wrong - faulty CFTR proteins cause thick, sticky mucus that damages lungs and other organs.

Ion Transport and Gradients

Every cell maintains an electrochemical gradient across its membrane - a combination of concentration differences and electrical charge differences. Typically, there's more positive charge outside and negative charge inside, creating the membrane potential.

The sodium-potassium pump (Na⁺/K⁺ ATPase) is the star player in maintaining these gradients. It pumps three sodium ions out for every two potassium ions pumped in, using ATP for energy. This creates the negative charge inside cells and accounts for a huge chunk of your basal metabolic rate.

The pump works through a sophisticated cycle. Sodium ions bind to high-affinity sites inside the cell, triggering ATP hydrolysis and a conformational change that opens the pump to the outside, releasing the sodium. Potassium ions then bind from outside, causing dephosphorylation and another shape change that pumps potassium into the cell.

This ion gradient is essential for nerve transmission, muscle contraction, and many other cellular processes. Without it, your cells would quickly lose their ability to respond to stimuli and maintain basic functions.

Energy Fact: The sodium-potassium pump uses so much ATP that it can account for up to 70% of energy consumption in nerve cells - it's literally one of your body's biggest energy expenses!