Breaking down and building up molecules

Cells rarely turn one molecule into another in a single jump. They work in small, coordinated steps, each carried out by its own enzyme.

Metabolic pathways

An organism’s metabolism is the whole set of chemical reactions going on inside it. The word also names particular sets of reactions, as in sugar metabolism or fat metabolism. Most metabolism involves breaking down or building organic molecules, which serve cells both as building materials and as stores of energy.

In cells, reactions are often linked into a series of steps, each catalyzed by its own specific enzyme. Such a series is a metabolic pathway. The product of one step becomes the substrate of the next, so a starting substrate passes through a chain of intermediate molecules before becoming the final product. In one pathway, for example, a series of enzymes attach phosphate groups, one after another, at different positions on a sugar.

Catabolic and anabolic reactions

Pathways fall into two groups. Reactions that break larger molecules into smaller ones are catabolic reactions, and they are often exergonic. Reactions that build larger molecules from smaller ones are anabolic reactions, also called biosynthetic reactions. Anabolic reactions are usually endergonic, so in cells they must be coupled to an exergonic reaction.

Why cells break molecules down

Catabolic reactions do two jobs for a cell.

The first is recycling building blocks. A protein is a chain of amino acids held together by peptide bonds. When a protein is misfolded or no longer needed, enzymes called proteases break those bonds, releasing amino acids that the cell uses to build new proteins. (The last part of this chapter shows how.)

The second is getting energy. Organic molecules store a lot of energy, but cells can’t use it directly. When a cell breaks down a molecule such as glucose, it captures part of the released energy in energy intermediates, molecules such as ATP that directly drive the cell’s endergonic reactions.

Two ways to make ATP

Cells make ATP from ADP in two main ways. Glycolysis, the catabolic pathway that splits glucose into two molecules of pyruvate (Chapter 7), shows the first. As its steps break and form covalent bonds, glycolysis creates molecules that readily hand a phosphate group to ADP. One of them, phosphoenolpyruvate (PEP), holds its phosphate in an unstable arrangement, and an enzyme transfers that phosphate to ADP:

PEP + ADP → pyruvate + ATP (ΔG = −7.5 kcal/mol)

On its own, making ATP from ADP is endergonic. It’s the reverse of ATP hydrolysis, so its ΔG is +7.3 kcal/mol. Here it’s coupled to removing PEP’s unstable phosphate, which releases more free energy than that. The combined ΔG is negative, so the reaction as a whole is exergonic and runs forward on its own: breaking down PEP pays for the new ATP.

Making ATP by having an enzyme transfer a phosphate directly from an organic molecule to ADP is called substrate-level phosphorylation.

The second way is chemiosmosis, in which energy stored in an electrochemical gradient, a difference in ion concentration and electric charge across a membrane, is used to make ATP from ADP and Pᵢ. Chapter 7 covers it in detail.

Check yourselfName the two jobs that catabolic reactions do for a cell. Why isn’t building a protein one of them?

Catabolic reactions recycle organic building blocks, such as amino acids from old proteins, and release energy that is captured in energy intermediates like ATP. Building a protein joins small molecules into a larger one, so it’s an anabolic reaction, not a catabolic one.