Biomolecules

Written and reviewed by Akanksha Tiwari, Physics & Chemistry faculty at UniDrill (M.Sc. Physics, Banaras Hindu University · 8 years teaching Class XI–XII science). Based on NCERT Chemistry Class XII, Chapter 10.

Why can a cow live on grass when you cannot?

Grass is cellulose and bread is starch. Both are chains of glucose, and both are broken down to glucose by water. Yet you digest bread and get nothing from grass. The difference is one tiny detail: in starch each glucose is joined to the next with the link pointing one way (α), and in cellulose with the link pointing the other way (β). Your enzymes fit the α link and nothing else.

That is the style of this whole chapter. A small difference in structure makes a huge difference in function. Four families of molecules do the work of life: carbohydrates (fuel and structure), proteins (the machines), vitamins (small helpers) and nucleic acids (the instructions).

Carbohydrates: what they are

Carbohydrates are optically active polyhydroxy aldehydes or ketones, or compounds that give these on hydrolysis. They are also called saccharides (from the Greek for sugar). Many fit the formula Cₓ(H₂O)ᵧ, which is why they were once called "hydrates of carbon".

Beyond the textbook. For the exam: carbohydrates are polyhydroxy aldehydes or ketones, loosely written Cₓ(H₂O)ᵧ. In reality: the formula is only a rough pattern. Rhamnose (C₆H₁₂O₅) is a true carbohydrate that does not fit it, and ethanoic acid (C₂H₄O₂) fits it but is not a carbohydrate at all. Why it matters: the structure (many –OH plus a carbonyl) defines a carbohydrate, not the formula.

They are classified by what happens on hydrolysis.

Monosaccharides are further named by carbon count (triose, tetrose, pentose, hexose) and by the carbonyl group: an aldose has –CHO and a ketose has >C=O. So glucose is an aldohexose, fructose a ketohexose and ribose an aldopentose.

Reducing and non reducing sugars. A sugar that reduces Tollens' reagent and Fehling's solution is a reducing sugar. All monosaccharides are reducing, ketoses included, because in alkaline solution a ketose such as fructose rearranges to an aldose (and back) through an enediol, so an aldehyde form is always available. Among disaccharides, maltose and lactose are reducing and sucrose is not (see below).

Glucose: how its structure was worked out

Glucose is made commercially by boiling starch with dilute H₂SO₄ at 393 K under 2 to 3 atm pressure, and from sucrose by boiling with dilute acid, which gives equal amounts of glucose and fructose.

(C₆H₁₀O₅)ₙ + nH₂O → nC₆H₁₂O₆

C₁₂H₂₂O₁₁ + H₂O → C₆H₁₂O₆ (glucose) + C₆H₁₂O₆ (fructose)

Each experiment on glucose gave one clue.

So glucose is the straight chain aldohexose HOCH₂–(CHOH)₄–CHO. In the Fischer drawing of D-(+)-glucose the –OH groups on C-2, C-4 and C-5 are on the right and on C-3 on the left.

D and L describe geometry, not the direction of rotation. The label D means the –OH on the lowest asymmetric carbon (C-5 for glucose) is on the right, as in D-(+)-glyceraldehyde. The sign in brackets, (+) or (−), is the direction in which the sugar rotates plane polarised light. They are independent: D-glucose is (+) while D-fructose is (−).

Why the open chain is not the whole story. Several observations cannot be explained by a free –CHO group.

All of this is explained by a cyclic hemiacetal: the –OH on C-5 adds to the aldehyde at C-1, closing a six membered ring (five carbons and one oxygen), called the pyranose form. The old aldehyde carbon, C-1, becomes a new asymmetric centre, the anomeric carbon. The two possible arrangements of –OH on C-1 give the α and β anomers, which differ only at C-1. In the Haworth drawing of D-glucose, the –CH₂OH on C-5 points up, the α anomer has the C-1 –OH pointing down (opposite face to –CH₂OH) and the β anomer has it pointing up (same face).

In water the α and β forms interconvert through the small amount of open chain present, and the rotation settles at a fixed value whichever form you started with. This is mutarotation.

Worked example: composition at equilibrium. α-D-glucose rotates by +112° and β-D-glucose by +19°. The equilibrium solution rotates by +52.5°. What percentage is α?

The common wrong step: averaging the two rotations as $(112 + 19)/2 = 65.5^\circ$. That assumes a 50:50 mixture, but the β form is more stable and dominates.

Fructose is a ketohexose with the C=O at C-2. It is D-(−)-fructose, laevorotatory, and it cyclises when the C-5 –OH attacks the C-2 ketone, giving a five membered ring (furanose) with four carbons and one oxygen. Free fructose exists mostly as a six membered ring, but when it is bound in sucrose it is in the five membered form.

Pause and predict: does cyclisation of glucose make its D label disappear?

Check your answer: no. D and L refer to C-5, the carbon that stays asymmetric. Ring closure only creates a new asymmetric centre at C-1 and does not change C-5, so the cyclic forms are still D-sugars (α-D and β-D).

Disaccharides: two sugars, one linkage

Two monosaccharides join through a glycosidic linkage, an oxygen bridge formed by loss of water between an anomeric –OH and an –OH of the other sugar.

The rule: a disaccharide is reducing only if at least one anomeric carbon is not tied up in the glycosidic bond, because that carbon can open up and show a free aldehyde.

Invert sugar. Sucrose rotates plane polarised light to the right, [α]D = +66.5°. On hydrolysis it gives D-(+)-glucose (+52.5°) and D-(−)-fructose (−92.4°). Fructose turns light further to the left than glucose turns it to the right, so the mixture is laevorotatory. The rotation has been inverted from + to −, so the mixture is called invert sugar.

Worked example: rotation of invert sugar. Find the specific rotation of the equimolar mixture of glucose and fructose from sucrose hydrolysis.

The common wrong step: adding the rotations instead of averaging them. A 1:1 mixture of the two sugars rotates as their average, not their sum.

Polysaccharides: storage and structure

All three polysaccharides here are built from glucose. The difference is the linkage and the branching.

Starch is the main store of carbohydrate in cereals, roots, tubers and some vegetables. Humans have enzymes that cut α-links but none for β-links, so we digest starch and glycogen but not cellulose. Cows and other ruminants have gut bacteria that make cellulase, which is why grass is food for them.

Pause and predict: a student says "sucrose is made of two reducing sugars, so sucrose must be a reducing sugar". What is wrong?

Check your answer: the reducing power of glucose and fructose comes from the free anomeric –OH. In sucrose the glycosidic bond uses both anomeric positions, so no free aldehyde or ketone can form and sucrose is non reducing.

Carbohydrates also supply D-ribose and 2-deoxy-D-ribose for nucleic acids, and chitin forms insect shells. Cotton, wood, paper and textiles come from cellulose.

Amino acids: the building blocks of proteins

An α-amino acid has an amino group and a carboxyl group on the same carbon (the α carbon), together with a hydrogen and a side chain R: H₂N–CHR–COOH. Only α-amino acids are obtained when natural proteins are hydrolysed. Every α-amino acid except glycine (R = H) has a chiral α carbon and is optically active, and nearly all natural ones have the L-configuration.

There are 20 standard amino acids. Of these, ten are essential: the body cannot make them and they must come from food.

A helpful grouping for the ten essential ones: three branched chain (Val, Leu, Ile), three basic (Lys, Arg, His) and four others (Thr, Met, Phe, Trp).

Acidic, basic or neutral. An amino acid is acidic if it has more –COOH than –NH₂ (aspartic acid, glutamic acid), basic if more –NH₂ than –COOH (lysine, arginine, histidine) and neutral if the numbers are equal.

Zwitterion. The –COOH is acidic and the –NH₂ is basic, so inside the same molecule the acid gives H⁺ to the base. The result is a dipolar ion, H₃N⁺–CHR–COO⁻, called a zwitterion, which explains why amino acids are crystalline, high melting, water soluble solids, not low melting organic compounds. The zwitterion is amphoteric: with acid it takes H⁺ onto the COO⁻ and becomes a cation, and with base it gives up H⁺ from NH₃⁺ and becomes an anion. At one particular pH, the isoelectric point, the molecule carries no net charge and does not move in an electric field.

Peptides and proteins

When the –COOH of one amino acid reacts with the –NH₂ of another and loses water, the result is an amide bond, –CO–NH–, called a peptide bond. Two amino acids give a dipeptide, three a tripeptide, and so on. A chain of more than about ten units is a polypeptide, and a polypeptide with more than 100 amino acids and a molecular mass above 10,000 u is a protein.

By convention the chain is written with the free –NH₂ end (N terminal) on the left. Gly-Ala and Ala-Gly are therefore different compounds.

Worked example: counting peptide bonds. Insulin has 51 amino acids in two chains (A with 21 and B with 30) joined by disulphide bridges. How many peptide bonds, and how many water molecules are needed to hydrolyse it fully?

The common wrong step: taking $51 - 1 = 50$. The two chains are separate polypeptides, so you subtract 1 for each chain. The disulphide bridges are –S–S– bonds, not peptide bonds.

Pause and predict: how many different tripeptides can you make from Gly, Ala and Val if each is used once?

Check your answer: six, because the order matters: Gly-Ala-Val, Gly-Val-Ala, Ala-Gly-Val, Ala-Val-Gly, Val-Gly-Ala and Val-Ala-Gly.

By shape. Proteins are of two broad types.

Four levels of protein structure

In the α-helix the chain coils like a right handed screw, and each C=O forms a hydrogen bond with an N–H four residues ahead in the same chain (intramolecular). In the β-pleated sheet the chains lie side by side, stretched out, held by hydrogen bonds between neighbouring chains (intermolecular).

Denaturation. Heat, a change in pH, urea, heavy metal ions or organic solvents break the weak hydrogen bonds and other interactions. The helix uncoils and the globule opens out, so the secondary and tertiary structures are destroyed and the protein loses its biological activity. The primary structure is untouched because peptide bonds are strong covalent bonds and are not broken. Boiling an egg coagulates the albumin, and bacteria turn milk to curd by making lactic acid.

Beyond the textbook. For the exam: denaturation destroys the secondary and tertiary structures but leaves the primary structure intact. In reality: the sequence holds the information needed to fold, so some denatured proteins do refold when the harsh condition is removed. A boiled egg, however, never un-boils, because the opened chains stick to one another instead of refolding. Why it matters: it shows that the primary structure decides the shape, and shape decides the function.

Enzymes: proteins that speed up life

Enzymes are biological catalysts, and almost all are globular proteins (a few are made of RNA). Each is highly specific for its substrate and reaction, and is usually named from the substrate with the ending –ase: maltase hydrolyses maltose, sucrase hydrolyses sucrose and urease hydrolyses urea.

The substrate binds to the enzyme's active site, an enzyme-substrate complex forms, and then it breaks down into product and free enzyme: E + S ⇌ ES → E + P. Enzymes work by lowering the activation energy. For the hydrolysis of sucrose, Ea is 6.22 kJ mol⁻¹ with acid but only 2.15 kJ mol⁻¹ with the enzyme sucrase.

Vitamins: small amounts, large effects

Vitamins are organic compounds needed in small amounts in the diet. Most cannot be made by the body (intestinal bacteria make some, including vitamin K and some of the B group), and a shortage causes a specific deficiency disease. The word "vitamine" was coined by Funk in 1912, from "vital amine". The final e was dropped when it became clear that not all vitamins are amines.

Fat soluble vitamins (A, D, E, K) dissolve in fats and oils and are stored in the liver and fatty tissue, so a shortage develops slowly. Water soluble vitamins (B group and C) are lost in urine and must be taken regularly. The exception is vitamin B12, which is water soluble yet stored in the liver.

Nucleic acids: the instructions

Nucleic acids are long chains of nucleotides. The two types, DNA and RNA, are found in the cell nucleus and carry heredity.

Complete hydrolysis gives three kinds of pieces: a pentose sugar, phosphoric acid and nitrogen containing bases. The sugar is β-D-2-deoxyribose in DNA and β-D-ribose in RNA. The bases are adenine (A), guanine (G) (purines, two fused rings) and cytosine (C), thymine (T), uracil (U) (pyrimidines, one ring). A, G and C occur in both DNA and RNA. T occurs only in DNA, and U only in RNA.

The phosphate joins the 5′ carbon of one sugar to the 3′ carbon of the next, which gives a sugar-phosphate backbone with the bases sticking out.

The double helix. In 1953 Watson and Crick showed that DNA consists of two antiparallel polynucleotide strands wound around each other in a right handed helix. The sugar-phosphate backbones are on the outside and the bases point inward and pair by hydrogen bonds: A pairs with T (two hydrogen bonds) and G pairs with C (three hydrogen bonds). The pairs fit because each pairs one purine with one pyrimidine, keeping the width constant. One full turn is about 3.4 nm long and holds 10 base pairs, and the helix is about 2 nm wide.

Worked example: base pair arithmetic. A DNA fragment has 100 base pairs, of which 40% are G≡C. Find the number of hydrogen bonds. Also, if a DNA sample is 28% adenine, find the other bases.

The common wrong step: applying A = T to RNA. In single stranded RNA there is no pairing rule that forces the amounts of A and U to be equal.

Function. DNA is the chemical basis of heredity. It copies itself (replication) before cell division, so each daughter cell gets identical DNA. RNA makes proteins under the instructions in DNA: DNA is transcribed to m-RNA, which is translated into protein on the ribosome with the help of r-RNA and t-RNA (which brings in the amino acids).

The flow in one line: DNA → (transcription) → m-RNA → (translation) → protein

Beyond the textbook. For the exam: DNA has thymine and RNA has uracil. In reality: cytosine slowly loses an amino group and turns into uracil. If DNA normally used uracil, the cell could not tell whether a U was a mistake or meant to be there. Because DNA uses thymine (which is 5-methyluracil), any U found in DNA is recognised as damage and repaired. Why it matters: the extra methyl group is a built in proofreading tag, not a random difference.

Exam traps

Key facts and numbers

60-second revision

Where this chapter connects

The cyclic hemiacetal form of glucose is carbonyl chemistry from Aldehydes, Ketones and Carboxylic Acids, and the peptide bond is an amide made from the amino group described in Amines. The idea that an enzyme lowers activation energy is explained numerically in Chemical Kinetics. In Biology, the same molecules are viewed from the cell's side in Biomolecules, and the way DNA is copied and read is developed in Molecular Basis of Inheritance.