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Biology · Glossary

What is Enzyme, substrate, active site?

Also known as: enzyme · substrate · active site · cofactor · coenzyme

Definition 15.4 High School Biology · Chapter 15 — Enzymes and the Phenotype

An enzyme is a protein that catalyses one chemical reaction: it makes the reaction run millions of times faster without being consumed. The molecule it transforms is its substrate; the reaction takes place in a pocket of the enzyme, the active site, whose shape and chemistry fit that substrate and no other. This specificity follows from the enzyme’s three-dimensional fold, hence from its amino acid sequence, hence from its gene.

Specificity. The active site is a pocket shaped for one substrate; a molecule of another shape cannot bind and is not transformed. Change the shape of the pocket — by a mutation — and the enzyme loses, or changes, its substrate.
Specificity. The active site is a pocket shaped for one substrate; a molecule of another shape cannot bind and is not transformed. Change the shape of the pocket — by a mutation — and the enzyme loses, or changes, its substrate.
Milk, yoghurt and a bottle of lactase drops. Whether an adult digests the milk depends on one allele; the yoghurt’s bacteria have already split much of the lactose; the drops supply the enzyme the gut lacks.
Milk, yoghurt and a bottle of lactase drops. Whether an adult digests the milk depends on one allele; the yoghurt’s bacteria have already split much of the lactose; the drops supply the enzyme the gut lacks.

Examples

Example 15.5 (Lactase)

Milk sugar, lactose, is split into two simple sugars by the enzyme lactase in the lining of the small intestine; without the split it passes undigested to the colon, where bacteria ferment it, with gas, cramps and diarrhoea as the result. All infants make lactase; in most of humanity its gene is switched off after weaning, and adults are lactose intolerant. In populations with a long history of dairying, an allele that keeps the gene active for life is common — 90% in northern Europe, 10% in eastern Asia. The lactase drops sold to the intolerant contain the same enzyme, made by fungi.

Example 15.8 (Phenylketonuria, and how a diet changes a phenotype)

About one newborn in ten thousand carries two non-working alleles of the gene for enzyme 1. Phenylalanine from food is not converted; its concentration in the blood rises twentyfold and it poisons the developing brain. Untreated, the child suffers severe intellectual disability. Detected at birth by a drop of blood on a card — every newborn is tested — and fed a diet almost free of phenylalanine, the same child develops normally. The genotype is unchanged; the phenotype, at every scale above the molecular one, is that of a healthy person. The environment, here the diet, decided.

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Definition 13.1 University Biology — Year 1 · Chapter 13 — Enzymes and Biochemical Catalysis

An enzyme is a protein (rarely an RNA) that catalyses a reaction: it increases the rate without being consumed and without changing the equilibrium. The molecules it acts on are its substrates; they bind in the active site, a cleft a few residues line, where the chemistry happens. Enzymes are specific — for one substrate or a family, for one bond, for one stereoisomer — and they are named for their substrate and reaction with the suffix -ase (lactase, DNA polymerase, succinate dehydrogenase), in six classes: oxidoreductases, transferases, hydrolases, lyases, isomerases, ligases. Many need a non-protein cofactor: a metal ion (Zn, Mg, Fe), or an organic coenzyme — NAD+\mathrm{NAD^+}, FAD, coenzyme A, most of them made from vitamins, which is what vitamins are for.

Free energy along a reaction. The enzyme (red) lowers the barrier of the transition state and leaves the difference between substrate and product — and hence the equilibrium — untouched.
Free energy along a reaction. The enzyme (red) lowers the barrier of the transition state and leaves the difference between substrate and product — and hence the equilibrium — untouched.
Hydrogen peroxide on a cut potato: catalase in the cells splits it into water and oxygen forty million times per second per enzyme molecule, and the oxygen froths out.
Hydrogen peroxide on a cut potato: catalase in the cells splits it into water and oxygen forty million times per second per enzyme molecule, and the oxygen froths out.

Examples

Example 13.4 (Three enzymes)

Lysozyme, in tears and egg white, strains a sugar ring of the bacterial wall into the shape of the transition state and cuts the chain: 10810^8-fold acceleration. Carbonic anhydrase, in red cells, holds a zinc ion that turns water into a hydroxide poised to attack CO2\mathrm{CO_2}: a million molecules a second, the fastest enzyme after catalase. Chymotrypsin, in the pancreatic juice, uses a serine made reactive by a histidine to cut proteins after aromatic residues: a hundred per second, with a covalent intermediate.

Example 13.8 (Enzymes compared)

enzymeKmK_m (mol/L\mathrm{mol}/\mathrm{L})kcatk_{\text{cat}} (s−1\mathrm{s}^{-1})kcat/Kmk_{\text{cat}}/K_m (L mol−1 s−1\mathrm{L}\,\mathrm{mol}^{-1}\,\mathrm{s}^{-1})
catalase2.5×10−22.5 \times 10^{-2}4×1074 \times 10^{7}1.6×1091.6 \times 10^{9}
carbonic anhydrase1.2×10−21.2 \times 10^{-2}1×1061 \times 10^{6}8×1078 \times 10^{7}
chymotrypsin1.5×10−21.5 \times 10^{-2}1007×1037 \times 10^{3}
lysozyme6×10−66 \times 10^{-6}0.58×1048 \times 10^{4}
DNA polymerase1×10−51 \times 10^{-5}151.5×1061.5 \times 10^{6}

Catalase and carbonic anhydrase work at the diffusion limit: every collision with substrate is productive. Chymotrypsin is slow but needs to be — it cuts a peptide bond, a far harder job than splitting peroxide.

Example 13.10 (Competition as medicine)

Methanol is harmless until the liver’s alcohol dehydrogenase turns it into formaldehyde and formic acid, which blind and kill. The treatment is ethanol: a competing substrate with a lower KmK_m, which keeps the enzyme busy while the methanol is excreted unchanged. Statins are competitive inhibitors, resembling the transition state, of the enzyme that commits carbon to cholesterol; sulfonamides resemble the substrate of a bacterial enzyme that makes folate, which humans do not make and so do not miss.

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