Metabolism: How Your Body Makes Energy

Metabolism is the sum of all chemical reactions in your body. Think of it as the body's engine — constantly breaking things down to release energy, and using that energy to build things up. There are two sides to metabolism: Catabolism — breaking large molecules DOWN to release energy. For example, breaking down glucose (sugar) from the food you eat. Anabolism — using energy to BUILD new molecules. For example, building muscle protein after exercise. The main goal of catabolism is to produce ATP (adenosine triphosphate) — the body's energy currency. Every time a cell needs to do work (contract a muscle, fire a nerve, pump ions), it spends ATP. Glucose is the body's favourite fuel. When you eat carbohydrates, they're broken down into glucose, which then goes through three linked processes to extract maximum energy.

Glycolysis (from Greek: "glykys" = sweet, "lysis" = splitting) happens in the cytoplasm (the watery fluid inside the cell) and does not need oxygen. The simple version: One glucose molecule (6 carbons) is split into two molecules of pyruvate (3 carbons each). What you get: - 2 ATP net (you invest 2 ATP to get 4 back — a net gain of 2) - 2 NADH — electron carriers (think of these as charged batteries that will be used later) Why it matters clinically: - Cancer cells rely heavily on glycolysis even when oxygen is available — this is called the Warburg effect. It's why PET scans (which detect high glucose uptake) can spot tumours. - Red blood cells have NO mitochondria, so glycolysis is their ONLY way to make ATP. - During intense exercise when oxygen can't keep up, muscle cells use glycolysis and produce lactic acid — causing that burning feeling.

After glycolysis, the two pyruvate molecules travel into the mitochondria (the cell's powerhouse). Here, each pyruvate is converted into a molecule called acetyl-CoA by an enzyme complex called pyruvate dehydrogenase. This step also releases CO₂ (which you breathe out) and produces more NADH (more charged batteries). Think of acetyl-CoA as the "ticket" that enters the next stage — the Krebs cycle. It's a 2-carbon molecule attached to a carrier (Coenzyme A). Clinical note: Vitamin B1 (thiamine) is a required helper (cofactor) for pyruvate dehydrogenase. In severe thiamine deficiency (seen in alcoholism or malnutrition), this step fails — pyruvate builds up and cannot enter the Krebs cycle. This causes serious conditions like Wernicke's encephalopathy (brain damage from thiamine deficiency).

The Krebs cycle (also called the citric acid cycle or TCA cycle) happens inside the mitochondrial matrix (the inner compartment of the mitochondria). It needs oxygen indirectly. The simple version: Acetyl-CoA (2 carbons) joins a 4-carbon molecule to make a 6-carbon molecule (citrate). The cycle then progressively strips carbons off, releasing CO₂, generating electron carriers, and regenerating the 4-carbon molecule to go round again. Per one acetyl-CoA, the Krebs cycle produces: - 3 NADH (charged electron carrier batteries) - 1 FADH₂ (another type of charged carrier) - 1 ATP (direct energy) - 2 CO₂ (waste gas you breathe out) Remember: one glucose makes two acetyl-CoA, so the cycle runs TWICE per glucose. Key insight: The Krebs cycle doesn't make much ATP directly — its main job is to generate lots of NADH and FADH₂. These go on to the next stage which makes the real ATP haul.

The electron transport chain (ETC) is located in the inner mitochondrial membrane. This is where most ATP is made — and it requires oxygen. The simple version: The NADH and FADH₂ "batteries" made in glycolysis and the Krebs cycle deliver their electrons to a series of protein complexes (Complexes I–IV) embedded in the inner mitochondrial membrane. As electrons pass through these complexes, energy is released and used to pump hydrogen ions (H⁺) across the membrane, creating a concentration gradient (like filling a dam with water). The H⁺ ions flow back down through an enzyme called ATP synthase — like water spinning a turbine — and this energy drives the production of large amounts of ATP. At the very end, electrons combine with oxygen (O₂) and hydrogen to form water (H₂O). This is why you need oxygen to breathe — it's the final electron acceptor. Total ATP yield from one glucose: - Glycolysis: ~2 ATP - Linking step + Krebs cycle: ~2 ATP - ETC: ~28–32 ATP - Grand total: ~30–36 ATP Why this matters clinically: - Cyanide poisoning blocks Complex IV — electrons cannot pass to oxygen — the ETC shuts down — cells cannot make ATP — rapid death. Treatment includes substances that accept electrons from other points in the chain. - Metformin (common diabetes drug) mildly inhibits Complex I — reducing glucose production in the liver.

The three stages work like an assembly line: 1. Glycolysis (no oxygen needed, cytoplasm) — glucose → pyruvate, small ATP gain 2. Krebs cycle (mitochondria) — acetyl-CoA → CO₂ + electron carriers 3. ETC (inner mitochondrial membrane, needs O₂) — electron carriers → massive ATP production Without oxygen: The ETC stops. Cells switch to anaerobic respiration, producing only 2 ATP per glucose (much less efficient). Lactic acid builds up — this happens during sprinting or when tissue is deprived of blood (ischaemia). What cells do with ATP: ATP is the universal energy currency. It powers muscle contraction, active transport across membranes, protein synthesis, nerve impulse transmission — essentially every energy-requiring process in the body.