Enzymes are built from amino acids. These small molecules link together in long chains to form proteins, and nearly all enzymes are proteins. Your body uses 20 standard amino acids in various combinations and sequences to construct every enzyme it needs, from those that digest food to those that copy DNA.
Amino Acids: The Core Units
Each amino acid has the same basic backbone: a central carbon atom bonded to a hydrogen atom, an amino group (containing nitrogen), and a carboxyl group (containing carbon and oxygen). What makes the 20 amino acids different from one another is a variable portion called the side chain. Some side chains are electrically charged, some are oily and water-repelling, some are bulky, and some are tiny. This chemical variety is what gives enzymes their remarkable range of abilities.
The 20 standard amino acids are alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine. Two additional amino acids, selenocysteine and pyrrolysine, have been discovered more recently. Selenocysteine shows up at the active site of several important enzymes, including ones that protect cells from oxidative damage.
How Amino Acids Connect
Amino acids join end to end through a chemical link called a peptide bond. During this reaction, the carboxyl group of one amino acid reacts with the amino group of the next, releasing a molecule of water in the process. The result is a growing chain, sometimes hundreds or thousands of amino acids long, called a polypeptide. Every enzyme starts as one or more of these polypeptide chains.
Inside your cells, this assembly happens on structures called ribosomes. The ribosome reads a strand of messenger RNA like a set of instructions, with every three-letter code (called a codon) specifying one amino acid. Transfer RNA molecules act as delivery trucks, each carrying the correct amino acid to match the current codon. The ribosome then stitches each new amino acid onto the growing chain, building the enzyme one unit at a time from start to finish.
From Chain to Functional Shape
A flat chain of amino acids is not yet an enzyme. The chain has to fold into a precise three-dimensional shape before it can do anything useful. Biochemists describe this folding in four levels.
- Primary structure is simply the sequence of amino acids in the chain, plus any strong sulfur-to-sulfur bonds (called disulfide bonds) between cysteine amino acids at different points in the chain. These disulfide bonds act like molecular staples, pinning distant parts of the chain together.
- Secondary structure refers to local patterns that form when the backbone of the chain coils into spirals or folds into flat sheets. These shapes are held in place by hydrogen bonds, a type of weak electrical attraction between nearby atoms in the backbone.
- Tertiary structure is the overall 3D shape of the entire chain. It results from interactions between the amino acid side chains: oily side chains cluster together away from water, charged side chains attract or repel one another, and hydrogen bonds form between compatible groups. All of these weak forces collectively lock the protein into a specific form.
- Quaternary structure applies when two or more folded chains (called subunits) come together to form a larger complex. Many enzymes are built from multiple subunits working as a team.
The final folded shape creates a small pocket or groove on the enzyme’s surface called the active site. This is where the enzyme grabs its target molecule and speeds up a chemical reaction. Only a handful of the enzyme’s amino acids sit directly in the active site, but an analysis of 178 enzyme active sites found that a small, recurring set of amino acids dominates catalytic roles. The rest of the chain exists largely to hold those critical few amino acids in exactly the right position.
Cofactors: The Non-Protein Helpers
Amino acids alone aren’t always enough. Many enzymes need an additional non-protein component, called a cofactor, to function. Without its cofactor, an enzyme is called an apoenzyme and is essentially inactive. With the cofactor attached, it becomes a complete, working unit known as a holoenzyme.
Cofactors come in three main forms. Metal ions like zinc, magnesium, copper, and iron are one type. Zinc, for example, is essential for an enzyme called carbonic anhydrase, which helps regulate the balance of carbon dioxide and bicarbonate in your blood. Metal ions can orient target molecules for a reaction, stabilize electrical charges, or promote interactions with water molecules.
The second type is a coenzyme, a small organic molecule that participates directly in the reaction and then floats away from the enzyme afterward. Many coenzymes are derived from vitamins. Thiamine pyrophosphate comes from vitamin B1, FAD comes from vitamin B2, and pyridoxal phosphate comes from vitamin B6. This is one reason vitamin deficiencies can disrupt so many bodily processes: without the vitamin, your body can’t build the coenzyme, and the enzyme can’t work.
The third type is a prosthetic group, which is similar to a coenzyme but stays permanently bound to the enzyme rather than detaching after each reaction cycle.
What Makes Enzymes Lose Their Shape
Because an enzyme’s function depends entirely on its folded shape, anything that disrupts that shape effectively destroys the enzyme. This process is called denaturation. Heat is the most familiar cause. Once the temperature exceeds an enzyme’s optimal range, the weak bonds holding its structure together break apart, the active site warps, and the reaction slows dramatically or stops entirely. This is why a high fever can be dangerous, and why cooking food changes its texture (the proteins in meat and eggs denature).
Extreme pH levels, whether very acidic or very alkaline, cause similar damage by disrupting the electrical charges on amino acid side chains. Each enzyme has a pH range where it works best. Digestive enzymes in your stomach thrive in highly acidic conditions, while enzymes in your small intestine prefer a more neutral environment. Move either enzyme into the other’s territory and it will unfold and stop functioning.
Not All Enzymes Are Proteins
While the vast majority of enzymes are built from amino acids, a small but important category is built from RNA instead. These RNA-based enzymes, called ribozymes, are constructed from nucleotides, the same building blocks that make up genetic material. Instead of folding a chain of amino acids, ribozymes fold a strand of RNA into a 3D shape capable of catalyzing chemical reactions. Some scientists think ribozymes may have been the earliest enzymes on Earth, guiding life’s chemistry before proteins evolved. Today, ribozymes still play key roles inside cells, including helping to assemble new proteins on the ribosome itself.