Anabolism, Catabolism, and Metabolic Pathways

Metabolism is the sum of all chemical reactions in a living organism; anabolism builds complex molecules from simpler ones using energy, catabolism breaks complex molecules down and releases energy, and reactions are organized in metabolic pathways, series of enzyme-controlled steps. In brief: photosynthesis and protein synthesis are anabolic, while respiration and digestion are catabolic. Energy released by catabolism is captured in ATP, which then powers anabolism. A pathway such as glycolysis converts glucose to pyruvate through ten enzyme-catalyzed steps.

Thousands of reactions take place in every cell, and metabolic pathways keep them organized. This guide defines metabolism, anabolism and catabolism, explains pathways, intermediates and the control of pathways by feedback inhibition, compares anabolic and catabolic processes, works through an energy-coupling example and corrects common mistakes.

What is metabolism?

The word metabolism comes from the Greek metabole, “change”. It describes all the chemical reactions that keep an organism alive: obtaining energy from nutrients, building and repairing cell components, and removing wastes. Metabolic reactions are catalyzed by enzymes, so they can proceed rapidly at body temperature. Metabolism has two complementary parts, anabolism and catabolism, and the speed of metabolism at rest is the basal metabolic rate.

What is anabolism?

Anabolic reactions build large molecules from small ones. They are endergonic: they need an input of energy, usually supplied by ATP. Examples:

• Photosynthesis: carbon dioxide and water to glucose.
• Protein synthesis: amino acids to proteins, with the formation of peptide bonds.
• Synthesis of glycogen, starch and cellulose from glucose.
• Synthesis of fats from glycerol and fatty acids.
• DNA replication and the synthesis of RNA from nucleotides.

Most anabolic reactions are condensation reactions, in which water is released. They allow growth, repair and the storage of energy.

What is catabolism?

Catabolic reactions break large molecules into smaller ones. They are exergonic: they release energy, part of which is captured in ATP and part lost as heat. Examples:

• Cell respiration: glucose to carbon dioxide and water.
• Digestion: starch, proteins and fats to sugars, amino acids and fatty acids and glycerol.
• Breakdown of glycogen, fat and proteins for energy.
• Fermentation.

Most catabolic reactions are hydrolysis reactions or oxidation reactions. The smaller products can be used as building blocks for anabolism or as fuel.

Anabolism and catabolism compared

What are metabolic pathways?

A metabolic pathway is a series of linked reactions in which the product of one reaction is the substrate for the next. Each step is catalyzed by a specific enzyme. The molecules formed between the start and the end are intermediates. Breaking a large change into small steps has advantages:

• Energy is released gradually, which allows it to be captured in ATP instead of being lost as heat.
• Each step can be controlled separately.
• Intermediates can be used in other pathways, so the cell can save resources.

Pathways can be linear, branched or cyclic. Glycolysis is a linear pathway in the cytoplasm that breaks down glucose in ten steps into two pyruvate molecules. The Krebs cycle and Calvin cycle are cyclic, because the starting molecule is regenerated at the end. Pathways are connected: for example, pyruvate from glycolysis enters the mitochondrion, and its products enter the Krebs cycle. In eukaryotic cells, enzymes of a pathway are often located together in one organelle, which increases efficiency.

How are metabolic pathways controlled?

Cells regulate pathways so that products are made only as needed. Two important mechanisms are:

• Feedback (end-product) inhibition: the final product of a pathway inhibits an enzyme at an early step of the same pathway, usually the first committed step. When there is too much product, the pathway slows down, and when the product is used, the inhibition is released. Example: ATP inhibits phosphofructokinase, a key enzyme in glycolysis, when the cell has enough ATP. This is a negative feedback loop at the molecular level.
• Control of enzyme amount: by regulating gene expression, so that cells make more or less of an enzyme.

Enzyme inhibition, including allosteric regulation, is explained in the article on enzyme inhibition.

Worked example: energy coupling and a feedback loop

Energy coupling

Making the peptide bond between two amino acids needs energy, and hydrolysis of ATP provides it. Suppose that forming a peptide bond requires about +17 kJ/mol, and hydrolysis of ATP releases about −30.5 kJ/mol (standard conditions).

1. Sum of the coupled reactions: +17 + (−30.5) = −13.5 kJ/mol.
2. Interpretation: the overall change is negative (exergonic), so the combined process can occur spontaneously, even though the peptide bond alone could not form.
3. Efficiency of the coupling: 17 ÷ 30.5 = 0.56, so about 56 percent of the ATP energy goes into the bond and the rest is lost as heat.

Feedback inhibition

A pathway makes isoleucine in five steps from threonine: A → B → C → D → E → isoleucine. Isoleucine inhibits enzyme 1, which converts threonine to A.

1. When the cell has little isoleucine, the inhibitor is absent. Enzyme 1 is active, and the pathway makes isoleucine.
2. As the isoleucine level rises, more of it binds to enzyme 1, and its activity falls. Less A, B, C, D and E are made, so isoleucine production decreases.
3. If the cell uses isoleucine for protein synthesis, its concentration falls, the inhibition is released and the pathway starts again.

The cell therefore avoids wasting energy and materials on making more isoleucine than it needs, by an automatic control that requires no extra signals. Inhibiting the first step is efficient, because the intermediates A to E do not accumulate unnecessarily.

How was metabolism studied?

Santorio Santorio weighed himself, his food and excreta for many years in the early seventeenth century, and showed that the body loses mass through “insensible perspiration”. Antoine Lavoisier linked respiration to combustion in the 1780s. Hans Krebs worked out the urea cycle (1932) and the citric acid cycle (1937). Fritz Lipmann showed that ATP links energy-releasing and energy-using reactions in the 1940s. Today, metabolism is studied in detail with isotopes and computer models of metabolic networks.

Which mistakes are common?

Mistake 1: Saying that anabolism releases energy

Anabolism uses energy. Catabolism releases it.

Mistake 2: Thinking that metabolism means only breakdown or digestion

It includes both the building and the breakdown reactions.

Mistake 3: Believing that all the energy released by catabolism is captured in ATP

Part of it is lost as heat, which warms endotherms.

Mistake 4: Mixing up feedback inhibition and substrate competition

In feedback inhibition, the end product of the pathway slows an earlier enzyme.