Jugami Biology

Biology · Lesson 12

Biomolecules and Enzymes

Every living thing is built from a few kinds of large molecules, and almost every reaction that keeps it alive is sped up by an enzyme.

This lesson covers why life is built on carbon and water, how small units join into big molecules, the four classes of biomolecules, and how enzymes work and are slowed down.

Sketch of an enzyme in pine ink with a raspberry substrate fitting into the notch of its active site.

1. Carbon and water

The large molecules of life are built on carbon. A carbon atom has four electrons in its outer shell, so it can form up to four covalent bonds, which lets it serve as the backbone of chains, branches and rings (see OpenStax 2.3).

Those molecules work in water. A water molecule is polar: its oxygen end is slightly negative and its hydrogen ends slightly positive. Neighboring molecules are attracted to each other by hydrogen bonds, which give water its special properties (see OpenStax 2.2):

2. Building and breaking big molecules

Most biological macromolecules are polymers built from small units called monomers. In dehydration synthesis, two monomers join by a covalent bond and a water molecule is released. In hydrolysis, a water molecule is added across the bond and breaks it (see OpenStax 3.1). Digestion uses hydrolysis to break food polymers into monomers your cells can absorb.

Explore: build and break a polymer

A chain of glucose monomers drawn as raspberry hexagons joined by bonds. An arrow shows a water molecule released when a bond forms, or added when a bond breaks.H₂O released

The drawing shows three glucose monomers just after the second bond formed. Turn on JavaScript to join and break bonds. In words:

  1. Join: each new bond between two monomers releases one water molecule.
  2. Break: hydrolysis adds one water molecule for each bond it breaks.
  3. A chain of six monomers has five bonds, so building it releases five water molecules, and breaking it down uses five.

Each hexagon is one glucose monomer. Drawn for this page from the description in OpenStax 3.1.

3. Carbohydrates

Carbohydrates are sugars and their polymers. Glucose, C6H12O6, is a simple sugar, or monosaccharide (see OpenStax 3.2). Long chains of glucose form three important polysaccharides (see OpenStax 3.2):

4. Lipids

Lipids are a varied group that are mostly nonpolar, so they do not mix with water. They include fats, oils, phospholipids and steroids (see OpenStax 3.3).

5. Proteins

Proteins do most of the work in cells: they act as enzymes, hormones such as insulin, structural fibers and antibodies. All proteins are made from the same 20 types of amino acids. A peptide bond, formed by dehydration synthesis, links one amino acid to the next (see OpenStax 3.4).

A protein's shape decides its function. Biologists describe four levels of structure (see OpenStax 3.4):

  1. Primary: the order of amino acids in the chain.
  2. Secondary: local folds, such as coils and pleated sheets, held by hydrogen bonds.
  3. Tertiary: the overall three-dimensional shape of one chain.
  4. Quaternary: how two or more chains fit together.

Heat, pH changes or chemicals can change that shape without breaking the sequence. This is denaturation, and a denatured protein loses its function. Sometimes it can refold when conditions return to normal; sometimes the change is permanent (see OpenStax 3.4).

6. Nucleic acids and ATP

DNA and RNA are nucleic acids, polymers of nucleotides that carry a cell's genetic instructions (see OpenStax 3.5). You meet them in detail in DNA and Genetics.

A close relative of the nucleotide powers the cell: ATP, adenosine triphosphate, has three phosphate groups and is the cell's main energy currency (see OpenStax 6.4).

7. Enzymes

Almost all enzymes are proteins that act as catalysts: they speed up reactions without being used up. They do this by lowering the activation energy, the energy needed to start a reaction (see OpenStax 6.5).

The molecule an enzyme acts on is its substrate, and it binds in a pocket called the active site. The amino acids lining the site create a very specific chemical environment, so each enzyme fits only certain substrates: substrate specificity. Scientists once pictured this as a rigid lock and key. The current view is induced fit: as the substrate binds, the enzyme changes shape slightly to grip it more tightly (see OpenStax 6.5).

Many enzymes need helpers. Cofactors are inorganic ions such as iron and magnesium; coenzymes are organic helpers, most often made from vitamins (see OpenStax 6.5).

Each enzyme works best at an optimum temperature and pH. Warming speeds reactions up to a point, but too much heat, or a pH far from the optimum, denatures the enzyme (see OpenStax 6.5). The protein-digesting enzyme pepsin works in the stomach, where acid keeps the contents at pH 1.5 to 3.5 (see OpenStax A&P 23.4). Trypsin works in the small intestine, where pancreatic juice is slightly basic, pH 7.1 to 8.2 (see OpenStax A&P 23.6).

Explore: temperature and pH

Rate of pepsin against pH, peaking on the acidic side, and rate against temperature, rising to an optimum then falling steeply where the enzyme denatures.RateOptimumAcidicNeutralBasicpHRateDenaturesOptimumColdHotTemperature

Turn on JavaScript to move the sliders. In words: rate rises toward the optimum and falls on either side of it. Past the temperature optimum the enzyme denatures, so the rate drops fast. Pepsin's pH curve peaks on the acidic side; trypsin's peaks on the slightly basic side.

Qualitative model: the curve shapes show the pattern, not measured values. Pattern from OpenStax 6.5.

Other molecules can slow an enzyme down. A competitive inhibitor looks enough like the substrate to bind the active site and block it. A noncompetitive inhibitor binds elsewhere on the enzyme and changes its shape so the active site no longer works. Adding more substrate can overcome a competitive inhibitor but not a noncompetitive one (see OpenStax 6.5).

Explore: two kinds of inhibitor

A competitive inhibitor fills the active site; the substrate waits outside.EnzymeActive siteSecond siteSubstrateCompetitiveinhibitor
A noncompetitive inhibitor in the second site bends the active site, so the substrate cannot fit.EnzymeActive siteSecond siteSubstrateNoncompetitiveinhibitor
  • No inhibitor: the substrate fits the active site and the reaction runs at full speed.
  • Competitive inhibitor: it looks enough like the substrate to sit in the active site and block it, so the reaction slows. More substrate: substrate now outcompetes the inhibitor for the active site, so the rate climbs back toward its maximum.
  • Noncompetitive inhibitor: it binds a second site and changes the enzyme's shape, so the active site no longer fits the substrate. More substrate: it still cannot fit the changed active site, so the maximum rate stays low.

Simplified and adapted from Figure 6.17 in OpenStax 6.5.

8. How do we know?

Step by step, chemists showed that the molecules of life obey ordinary chemistry, then learned to see their shapes.

  1. 1828 Friedrich Wöhler reports making urea, a compound of living things, in the laboratory, in a paper titled “On the artificial formation of urea”. (Wöhler)
  2. 1894 Emil Fischer studies how a molecule's three-dimensional configuration affects enzyme action, the paper behind the lock-and-key idea. (Fischer)
  3. 1897 Eduard Buchner shows that yeast extract with no living cells can turn sugar into alcohol. He wins the 1907 Nobel Prize for this cell-free fermentation. (Nobel Prize)
  4. 1913 Leonor Michaelis and Maud Menten describe how an enzyme's rate depends on how much substrate is present. (Johnson & Goody)
  5. 1926 James Sumner isolates and crystallizes the enzyme urease. He shares the 1946 Nobel Prize for showing that enzymes can be crystallized. (Sumner; Nobel Prize)
  6. 1955 Frederick Sanger's group reports the disulphide bonds of insulin. He wins the 1958 Nobel Prize for his work on protein structure, especially insulin. (Ryle and colleagues; Nobel Prize)
  7. 1958 Daniel Koshland proposes a new theory of enzyme specificity, now called induced fit. The same year, John Kendrew's team publishes a three-dimensional model of myoglobin from X-ray analysis. (Koshland; Kendrew)
  8. 1962 Kendrew and Max Perutz share the Nobel Prize for their studies of the structures of globular proteins. (Nobel Prize)
  9. 2020 Demis Hassabis and John Jumper present AlphaFold2, an AI model that predicts protein structure from sequence, described in Nature in 2021. It has predicted structures for virtually all 200 million known proteins. (Jumper and colleagues; Nobel Prize)

Quiz: Biomolecules check

Talk about it

  1. Starch and cellulose are both made of glucose. Why can you digest one but not the other?
  2. Why does a high fever become dangerous, in terms of proteins?
  3. Butter is solid and olive oil is liquid at room temperature. Explain using fatty acid structure.
  4. A drug works by blocking an enzyme's active site. What could a cell do to overcome it?

Sources

  1. Clark, M. A., Douglas, M. and Choi, J. (2018). 2.2 Water. Biology 2e. OpenStax. States water's polarity, hydrogen bonding, cohesion, solvent role, and specific heat of one calorie per gram per degree Celsius, about five times that of sand. openstax.org
  2. Clark, M. A., Douglas, M. and Choi, J. (2018). 2.3 Carbon. Biology 2e. OpenStax. States that carbon can form up to four covalent bonds. openstax.org
  3. Clark, M. A., Douglas, M. and Choi, J. (2018). 3.1 Synthesis of Biological Macromolecules. Biology 2e. OpenStax. openstax.org
  4. Clark, M. A., Douglas, M. and Choi, J. (2018). 3.2 Carbohydrates. Biology 2e. OpenStax. Gives glucose as C6H12O6. openstax.org
  5. Clark, M. A., Douglas, M. and Choi, J. (2018). 3.3 Lipids. Biology 2e. OpenStax. States that steroids have four linked carbon rings. openstax.org
  6. Clark, M. A., Douglas, M. and Choi, J. (2018). 3.4 Proteins. Biology 2e. OpenStax. States that all proteins are made from 20 types of amino acids. openstax.org
  7. Clark, M. A., Douglas, M. and Choi, J. (2018). 3.5 Nucleic Acids. Biology 2e. OpenStax. openstax.org
  8. Clark, M. A., Douglas, M. and Choi, J. (2018). 6.4 ATP: Adenosine Triphosphate. Biology 2e. OpenStax. States that ATP has three phosphate groups. openstax.org
  9. Clark, M. A., Douglas, M. and Choi, J. (2018). 6.5 Enzymes. Biology 2e. OpenStax. Covers activation energy, specificity, induced fit, temperature and pH, inhibition and cofactors, with Figure 6.17. openstax.org
  10. Betts, J. G. and colleagues (2022). 23.4 The Stomach. Anatomy and Physiology 2e. OpenStax. States a stomach pH of 1.5 to 3.5. openstax.org
  11. Betts, J. G. and colleagues (2022). 23.6 Accessory Organs in Digestion: The Liver, Pancreas, and Gallbladder. Anatomy and Physiology 2e. OpenStax. States a pancreatic juice pH of 7.1 to 8.2 and that trypsin acts in the small intestine. openstax.org
  12. Wöhler, F. (1828). Ueber künstliche Bildung des Harnstoffs. Annalen der Physik 88(2): 253–256. doi:10.1002/andp.18280880206
  13. Fischer, E. (1894). Einfluss der Configuration auf die Wirkung der Enzyme. Berichte der deutschen chemischen Gesellschaft 27(3): 2985–2993. doi:10.1002/cber.18940270364
  14. The Nobel Prize in Chemistry 1907: Eduard Buchner, “for his biochemical researches and his discovery of cell-free fermentation”. Facts page, which dates the yeast-extract discovery to 1897. nobelprize.org
  15. Johnson, K. A. and Goody, R. S. (2011). The original Michaelis constant: translation of the 1913 Michaelis–Menten paper. Biochemistry 50(39): 8264–8269. doi:10.1021/bi201284u
  16. Sumner, J. B. (1926). The isolation and crystallization of the enzyme urease. Journal of Biological Chemistry 69: 435–441. doi:10.1016/S0021-9258(18)84560-4. The Nobel Prize in Chemistry 1946: one half to James B. Sumner, “for his discovery that enzymes can be crystallized”. nobelprize.org
  17. Ryle, A. P., Sanger, F., Smith, L. F. and Kitai, R. (1955). The disulphide bonds of insulin. Biochemical Journal 60(4): 541–556. doi:10.1042/bj0600541. The Nobel Prize in Chemistry 1958: Frederick Sanger, “for his work on the structure of proteins, especially that of insulin”. nobelprize.org
  18. Koshland, D. E. (1958). Application of a theory of enzyme specificity to protein synthesis. PNAS 44(2): 98–104. doi:10.1073/pnas.44.2.98
  19. Kendrew, J. C. and colleagues (1958). A three-dimensional model of the myoglobin molecule obtained by X-ray analysis. Nature 181: 662–666. doi:10.1038/181662a0. The Nobel Prize in Chemistry 1962: Max F. Perutz and John C. Kendrew, “for their studies of the structures of globular proteins”. nobelprize.org
  20. Jumper, J. and colleagues (2021). Highly accurate protein structure prediction with AlphaFold. Nature 596: 583–589. doi:10.1038/s41586-021-03819-2. The Royal Swedish Academy of Sciences (2024). Press release: The Nobel Prize in Chemistry 2024, which dates AlphaFold2 to 2020 and states about 200 million proteins. nobelprize.org