Biomolecules

Written and reviewed by Anjali Sharma, Biology faculty at UniDrill (M.Sc. Botany, Banaras Hindu University · 8 years teaching NCERT Biology). Based on NCERT Biology Class XI, Chapter 9.

What is a leaf, a liver or a bacterium actually made of?

Grind up a vegetable, a piece of liver or a paste of bacteria, and you will find the same elements the Earth's crust has. Yet a rock is not alive. What changes is the proportion, and the molecules those elements are assembled into. This chapter is the chemistry of life: the small molecules cells use as building blocks, the giant molecules they build from them, and the enzymes that run every reaction in between.

The elements of life

Elemental analysis of living tissue gives the same list of elements as a sample of the Earth's crust, but with a very different balance. Life is rich in hydrogen, carbon and oxygen, and it is nearly empty of silicon, which is abundant in rocks.

How we analyse a living tissue

The method is simple enough to picture. Grind a piece of tissue in trichloroacetic acid (Cl₃CCOOH) using a mortar and pestle to get a thick slurry, then strain it through cheesecloth or cotton. Two fractions come out, and everything in the chapter hangs on the difference.

A second experiment gives the inorganic part. Weigh fresh tissue (wet weight), dry it (dry weight), then burn it. The carbon compounds oxidise to CO₂ and water vapour, and what is left is ash, containing inorganic elements such as calcium and magnesium. Inorganic compounds, such as sulphate and phosphate, are also present in the acid-soluble fraction. Typical inorganic constituents include sodium, potassium, calcium and magnesium ions, and compounds such as NaCl, CaCO₃, phosphate and sulphate.

The lipid exception. Lipids have small molecules (well under 1,000 Da), so why do they end up in the acid-insoluble fraction? Because when you grind a cell, its membranes break into little vesicles that are not soluble in water, and these settle along with the proteins, nucleic acids and polysaccharides. So lipids are in that fraction by accident, and they are not strictly macromolecules.

Water is the most abundant chemical in living organisms. A typical cell is made of the following.

Amino acids: the 20 letters of protein

An amino acid has an amino group and an acidic (carboxyl) group on the same carbon, the α-carbon, which makes it an α-amino acid. That carbon carries four things (a substituted methane): hydrogen, –COOH, –NH₂ and a variable R group. If R is hydrogen the amino acid is glycine, if it is a methyl group it is alanine, and if it is hydroxymethyl it is serine. Only 20 types of amino acids occur in proteins.

Both the –NH₂ and –COOH groups are ionisable, so the structure of an amino acid changes with pH. The form in which both groups are charged, H₃N⁺–CHR–COO⁻, is the zwitterion.

Lipids, nitrogen bases and metabolites

Lipids are generally water-insoluble. A fatty acid is an R group (1 to 19 carbons) with a –COOH group. Palmitic acid has 16 carbons including the carboxyl carbon, and arachidonic acid has 20. Fatty acids are saturated (no double bond) or unsaturated (one or more C=C bonds). Glycerol is trihydroxypropane. A triglyceride is glycerol joined to three fatty acids, and such compounds are called fats or oils depending on melting point. Oils melt at lower temperatures, which is why gingelly oil stays liquid in winter. Phospholipids, such as lecithin, contain a phosphate group and are found in cell membranes.

Nitrogen bases are heterocyclic rings: adenine, guanine, cytosine, uracil and thymine. Their naming depends on what is attached.

Pause and predict: adenosine has a phosphate group added to its sugar. Is the product a nucleoside or a nucleotide, and what is it called?

Check your answer: a nucleotide, called adenylic acid. The phosphate is exactly what turns a nucleoside into a nucleotide.

Primary and secondary metabolites. The compounds above (amino acids, sugars, bases) are primary metabolites because their roles in normal physiology are known. Plants, fungi and microbes also make thousands of compounds whose roles are less clear, called secondary metabolites.

Beyond the textbook. For the exam: secondary metabolites are compounds whose roles in normal physiology are not obvious, and many are useful to humans. In reality: they are not useless by-products. Many are chemical defences, such as the toxins ricin and abrin, and a plant can make a lifesaving drug as a side effect of that defence: vinblastine comes from the Madagascar periwinkle and is used against certain cancers. Why it matters: that explains why a table of poisons, pigments and drugs appears in a chapter on the chemistry of life.

Macromolecules and the bonds that build them

The acid-insoluble fraction contains four types of organic compounds, three of which are true polymers: proteins, nucleic acids and polysaccharides, with lipids tagging along. Each polymer is built from its own monomers joined by its own bond.

Inside a nucleotide, the base is attached to the sugar by an N-glycosidic bond. The table pulls the bond names together so you can sort them quickly, and the N-glycosidic link is a favourite one-line question.

Proteins: the workers

A protein is a polypeptide, a linear chain of amino acids linked by peptide bonds. It is a heteropolymer because it has several kinds of monomers. A homopolymer would repeat a single monomer. Dietary proteins are the source of essential amino acids, the ones the body cannot make for itself. Proteins do many jobs.

Two records to memorise. Collagen is the most abundant protein in the animal world, and RuBisCO (ribulose bisphosphate carboxylase oxygenase) is the most abundant protein in the whole biosphere.

Four levels of protein structure. A protein is built up in stages, and each stage adds a new kind of folding.

The tertiary structure is essential for biological activity, because the shape is what lets an enzyme or a receptor work. The standard quaternary example is adult human haemoglobin, with four subunits: two α and two β.

Pause and predict: a protein is a single polypeptide folded into a globular shape. What is the highest level of structure it can have?

Check your answer: tertiary. Quaternary structure needs at least two polypeptide chains assembled together.

Polysaccharides: sugar chains

Polysaccharides are long chains of monosaccharides. Cellulose is a homopolymer of glucose and the main structural material in plant cell walls (paper and cotton are cellulose). Starch is the storage form in plants, and glycogen is the storage form in animals. Inulin is a polymer of fructose. In the branched glycogen chain, the right end is the reducing end and the left end is the non-reducing end. More complex polysaccharides contain amino-sugars, such as glucosamine and N-acetyl galactosamine, and chitin, in the exoskeleton of arthropods, is one of them.

The iodine test separates starch from cellulose. Starch forms helical structures that can hold iodine molecules, giving a blue colour. Cellulose does not form complex helices, so it cannot hold iodine and gives no blue.

Beyond the textbook. For the exam: starch holds iodine because it is helical, and cellulose does not. In reality: both are chains of glucose, but they are joined by different linkages: α linkages in starch, which curl into a helix, and β linkages in cellulose, which keep the chains straight and let them pack into tough fibres. Why it matters: that is also why humans digest starch but cannot digest cellulose, since we do not make an enzyme that breaks β linkages.

Nucleic acids

Nucleic acids are polynucleotides. Each nucleotide has three parts: a nitrogenous base, a pentose sugar (ribose in RNA, 2′-deoxyribose in DNA) and phosphate. The bases fall into two families.

Enzymes: why life does not happen at geological speed

Almost all enzymes are proteins. A few nucleic acids also act as catalysts, and are called ribozymes. Like any protein, an enzyme has primary, secondary and tertiary structure, and when the chain folds it makes crevices. One such pocket is the active site, where the substrate fits and the reaction happens.

Why we need them. Take the reaction CO₂ + H₂O ⇌ H₂CO₃. Without an enzyme, about 200 molecules of carbonic acid form per hour. With carbonic anhydrase, about 600,000 molecules form every second, an acceleration of about 10 million times. A metabolic pathway is a series of such steps. The conversion of glucose to two molecules of pyruvic acid goes through ten enzyme-catalysed reactions.

A rule of thumb for chemical reactions: the rate roughly doubles (or halves) for every 10°C rise (or fall) in temperature. Inorganic catalysts keep working at high temperature and pressure, but enzymes are usually damaged above about 40°C. The exception is enzymes from thermophiles, organisms of hot vents and sulphur springs, which stay stable at 80 to 90°C.

How an enzyme works. The substrate (S) binds the active site and forms an enzyme-substrate (ES) complex. The enzyme changes shape slightly to grip the substrate more tightly, which is called induced fit. A short-lived transition state follows, and then an enzyme-product (EP) complex, which releases the product (P) and the unchanged enzyme.

The catalytic cycle in one line: E + S → ES → EP → E + P

Every reaction must climb an energy hill before it can proceed. The height of that hill is the activation energy, the energy difference between the substrate and its transition state. Enzymes work by lowering the activation energy. If the product has less energy than the substrate, the reaction is exothermic, and if it has more, it is endothermic.

Beyond the textbook. For the exam: an enzyme lowers activation energy and works by induced fit. In reality: an enzyme speeds up the approach to equilibrium but does not change where the equilibrium lies, and it is not consumed in the process. Why it matters: this is why an enzyme can run a reaction in either direction depending on conditions, and why one enzyme molecule can serve over and over again.

What affects enzyme speed. Each enzyme has an optimum temperature and an optimum pH, and activity falls on both sides. At low temperature the enzyme is only temporarily inactive, and it recovers when warmed. At high temperature it is denatured and the loss is permanent. With more substrate, the rate rises until it hits the maximum velocity, V_max, at which every enzyme molecule is busy. The substrate concentration at half of V_max is the K_m.

Inhibitors. A chemical that shuts off enzyme activity by binding to it is an inhibitor. When the inhibitor closely resembles the substrate, it fits the active site and blocks it, which is competitive inhibition. The standard example is malonate, which resembles succinate and blocks succinic dehydrogenase. Competitive inhibitors are used to control bacterial pathogens.

Pause and predict: a competitive inhibitor is slowing an enzyme. What happens if you flood the reaction with substrate?

Check your answer: the rate climbs back towards V_max. Substrate molecules outnumber inhibitor molecules and win the competition for the active site.

Beyond the textbook. For the exam: a competitive inhibitor resembles the substrate, as malonate resembles succinate. In reality: this is the principle behind sulpha drugs. They resemble a molecule bacteria need to make folic acid, so they jam a bacterial enzyme, and human cells, which take folic acid from food, are largely unharmed. Why it matters: it shows how a textbook idea becomes medicine.

The six classes of enzymes

The international classification groups enzymes into six classes by the reaction they catalyse. Each is divided into subclasses, and every enzyme has a four-digit code.

Order of the classes: Over The Hill Life Is Lovely gives Oxidoreductases, Transferases, Hydrolases, Lyases, Isomerases, Ligases.

Cofactors: the helpers

Some enzymes work only with a non-protein partner called a cofactor. The protein part is the apoenzyme, and apoenzyme plus cofactor is the complete, active enzyme (holoenzyme). If the cofactor is removed, catalytic activity is lost.

Exam traps

60-second revision

Where this chapter connects

• Previous: Cell: The Unit of Life shows the membranes, ribosomes and chromatin that are built from the molecules in this chapter.
• Next: Cell Cycle and Cell Division puts DNA and protein to work as cells divide.
• Related: Photosynthesis in Higher Plants is where RuBisCO does its job, Respiration in Plants follows the glucose to pyruvic acid pathway, and Molecular Basis of Inheritance takes the nucleotide and the purine and pyrimidine families much further.