Metabolism, ATP and Enzymes: How Cells Capture and Use Energy

1Overview

A sprinter explodes off the blocks, a student concentrates on a difficult problem, a hair grows a fraction of a millimetre overnight: each involves thousands of chemical reactions running in the right place at the right moment. The sum of all of them is called metabolism. This lesson explains the two directions metabolism can run, the molecule that carries its energy, the stepwise way glucose is dismantled to make that molecule, and the protein catalysts called enzymes that make every step fast enough for life.

2Two directions: catabolism and anabolism

Catabolic reactions break large organic molecules into smaller ones and release energy that was stored in their chemical bonds. Digestion of starch, breakdown of glucose and breakdown of fat for fuel are catabolic. Anabolic reactions do the reverse: they join small molecules into larger ones and require an input of energy. Building protein from amino acids, storing glucose as glycogen and laying down new bone matrix are anabolic.

In terms of Lesson 1, catabolism is mostly hydrolysis and oxidation, and anabolism is mostly dehydration synthesis. The two are linked by a balance sheet. If catabolism releases more energy than anabolism and other work use, the excess is stored, largely as fat. If it releases less, the body draws on stored energy.

Hormones tilt the balance. Catabolic hormones include cortisol (released in stress, raises blood glucose), glucagon (breaks down liver glycogen) and epinephrine. Anabolic hormones include insulin, growth hormone and IGF, and the sex hormones testosterone and estrogen, which support muscle, bone and fat deposition. Lesson 7 returns to these.

3ATP: production and use

Cells cannot burn glucose directly in a single step; the energy would be released as useless heat. Instead they capture it in small packets in ATP (adenosine triphosphate). The molecule is a nucleotide: adenine, ribose and three phosphate groups. The bond between the second and third phosphate is the high-energy bond. Hydrolyzing it gives ADP and inorganic phosphate (P_i) plus energy that can be coupled to work; adding the phosphate back (phosphorylation) recharges the molecule.

Only about 40% of the energy released by catabolism is captured in ATP. The remaining roughly 60% is released as heat, which helps explain why working muscle makes the body warm and why shivering raises temperature. ATP is used for three broad categories of work:

• Mechanical work: muscle contraction, movement of chromosomes and cilia.
• Transport work: active transport such as the sodium-potassium pump, which consumes most of a neuron's ATP (Lesson 3).
• Chemical work: driving the anabolic reactions that build macromolecules.

Phosphorylation also regulates proteins

Cells can transfer phosphate from ATP to other molecules. When glucose enters a cell it is phosphorylated, which traps it inside, and phosphorylation of proteins can switch them on or off. In this way ATP is both an energy carrier and a signalling tool.

4Redox reactions and electron carriers

Most energy transfer in metabolism involves moving electrons, usually as hydrogen atoms (an electron plus a proton). Oxidation is the loss of an electron and reduction is the gain of one; the two always occur together, so the electron donor is oxidized while the recipient is reduced. Enzymes catalyze these steps, and helper molecules called coenzymes accept the hydrogen atoms. The two most common are NAD and FAD; their reduced forms, NADH and FADH₂, are shuttles that carry energy to the place where most ATP is made.

5Cellular respiration: how ATP is made from glucose

Glucose is the main fuel for ATP production. Its complete aerobic breakdown is called cellular respiration and has three stages.

1. Glycolysis (cytoplasm). One glucose is first phosphorylated (using 1 ATP, trapping it in the cell) and then, after a second ATP is invested, split into two three-carbon pieces. Each piece is oxidized, reducing NAD⁺ to NADH, and ATP is made by transferring phosphate to ADP. The products are 2 pyruvate, 4 ATP (a net of 2 after the 2 invested) and 2 NADH. Glycolysis needs no oxygen.
2. Pyruvate oxidation and the Krebs (citric acid) cycle (mitochondrial matrix). Pyruvate enters the mitochondrion and is converted to two-carbon acetyl CoA, releasing CO₂ and making NADH. Acetyl CoA combines with oxaloacetate to form citrate, and the cycle regenerates oxaloacetate while releasing more CO₂. Each turn yields 3 NADH, 1 FADH₂ and 1 ATP (through GTP); because one glucose gives two pyruvate, the totals per glucose are doubled.
3. Electron transport chain and oxidative phosphorylation (inner mitochondrial membrane). NADH and FADH₂ pass electrons along a series of protein complexes. The energy released pumps H⁺ into the space between the membranes, building a gradient. The H⁺ then flows back through ATP synthase, which spins like a turbine and attaches phosphate to ADP. Oxygen is the final electron acceptor, combining with electrons and H⁺ to make water. If oxygen is absent, electron flow stops.

NADH yields about 3 ATP and FADH₂ about 2, because FADH₂ enters the chain at a later point. The OpenStax textbook gives a net of 36 ATP per glucose for the full aerobic pathway; the large majority comes from the electron transport chain, which is why oxygen supply matters so much.

When oxygen is short: fermentation

During intense exercise, muscles use ATP faster than oxygen can be delivered. Glycolysis continues, and pyruvate is converted to lactic acid. This regenerates the NAD⁺ that glycolysis needs, so ATP production can continue for seconds to a few minutes. Red blood cells have no functional mitochondria and always rely on this route. Lactate diffuses into the blood and travels to the liver, where it can be converted back to pyruvate or glucose (the Cori cycle).

Other fuels and gluconeogenesis

Triglycerides are used mainly for energy through beta-oxidation, and proteins are broken to amino acids that can be rebuilt into proteins or used for ATP. The Krebs cycle supplies starting materials for breaking down proteins and fats. Excess glucose is stored as glycogen in liver and skeletal muscle, or converted to fat. During fasting the liver makes new glucose from pyruvate, lactate, glycerol or amino acids by gluconeogenesis, because the brain and some other organs depend heavily on glucose.

6Fed and fasting: how the body switches between building and burning

Metabolism is not constant; it shifts with the time since the last meal, and hormones direct the switch.

• Fed state (after a meal). Rising blood glucose stimulates beta cells of the pancreas to release insulin. Insulin promotes glucose uptake, glycolysis, storage of glucose as glycogen (glycogenesis) and the building of fats and proteins. The state is mainly anabolic.
• Fasting state (between meals). Falling glucose lowers insulin and raises glucagon. Glucagon stimulates the liver to break glycogen into glucose (glycogenolysis) and to make new glucose (gluconeogenesis), and it stimulates the breakdown of fat. Cortisol and epinephrine push in the same direction during stress. The state is mainly catabolic.

The outcome is that blood glucose stays within a narrow range even though meals are irregular, which matters because neurons and red blood cells depend almost entirely on glucose. The mechanism is the negative feedback loop described in Lesson 3 and examined in detail in Lesson 7.

Metabolism and body heat

Because about 60% of the energy released in catabolism escapes as heat, metabolism is the body's heater. Thyroid hormones raise the basal metabolic rate, increasing ATP production and oxygen use and releasing more heat (the calorigenic effect). An overactive thyroid therefore causes heat intolerance, sweating and weight loss, whereas an underactive thyroid causes cold intolerance and weight gain. Shivering, in which muscles use ATP to contract without moving the body, is a deliberate way of turning ATP into heat when core temperature falls.

7Enzymes: biological catalysts

Left alone, most reactions in the body would proceed far too slowly at 37°C. A catalyst speeds a reaction without being consumed, and in the body the important catalysts are enzymes, which are proteins (a few are RNA). Each reaction needs a minimum energy to begin, the activation energy. Enzymes lower it.

An enzyme has an active site, a small pocket whose shape and chemistry fit a particular substrate. Two models describe the fit.

• Lock-and-key model: the substrate fits the rigid active site exactly, like a key in a lock. It explains specificity.
• Induced-fit model: the active site is flexible and adjusts slightly as the substrate binds, like a glove moulding to a hand. This is the model favoured by current textbooks because it also explains how binding strains the substrate bonds and lowers activation energy.

Each enzyme typically catalyzes one reaction or one type of reaction. Many need a non-protein helper: cofactors (often metal ions) or coenzymes (organic molecules such as NAD and FAD, which are derived from vitamins).

8What affects and regulates enzymes

Because an enzyme is a protein whose function depends on shape (Lesson 1), conditions that change shape change activity.

Cells also regulate enzymes deliberately, which is how metabolism responds to need.

• Competitive inhibition: a molecule resembling the substrate occupies the active site and blocks it.
• Allosteric regulation: a regulator binds a different site and changes the enzyme's shape, switching it up or down.
• Feedback inhibition: the end product of a pathway inhibits an early enzyme, so the cell stops making more than it needs. This is negative feedback at the molecular scale (Lesson 3).
• Inactive precursors (zymogens): some enzymes are made as inactive forms and activated where needed. Pepsinogen is activated to pepsin by stomach acid, and the pancreas secretes trypsinogen and other protein-digesting enzymes inactive, to prevent digesting the pancreas itself.
• Gene-level control and hormones: insulin and glucagon change which enzymes of glucose metabolism are active, and the cell makes more or fewer copies of an enzyme by changing gene expression (Lesson 4).

In real life. Many drugs are enzyme inhibitors. Aspirin and ibuprofen reduce production of prostaglandins by blocking the enzymes that make them. Enzyme tests are also used in diagnosis. Lactose intolerance, in which the enzyme that hydrolyzes milk sugar is deficient, shows what happens when one enzyme is missing.

Metabolism is therefore a controlled, enzyme-driven network. Its currency is ATP, its main fuel is glucose, its regulation is largely feedback, and it supports everything the later lessons describe, from nerve impulses to muscle contraction to digestion.

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