Biomolecules

In this chapter: classification of carbohydrates, preparation and structure of glucose (open chain and cyclic), anomers and Haworth structures, fructose, disaccharides and polysaccharides, amino acids and the peptide bond, levels of protein structure, denaturation, enzymes, vitamins, nucleic acids, and a short note on hormones.

Carbohydrates

Carbohydrates are optically active polyhydroxy aldehydes or ketones, or compounds that give these on hydrolysis. Many fit the formula C_x(H₂O)_y, but the formula alone is not a definition: rhamnose (C₆H₁₂O₅) is a carbohydrate that does not fit it, and acetic acid (C₂H₄O₂) fits it but is not a carbohydrate.

• Monosaccharides cannot be hydrolysed further: glucose, fructose, ribose. They are aldoses (with -CHO) or ketoses (with C=O), and trioses to heptoses by carbon count. Glucose is an aldohexose; fructose is a ketohexose.
• Oligosaccharides give 2 to 10 monosaccharide units on hydrolysis. Disaccharides such as sucrose, maltose and lactose give two.
• Polysaccharides give a large number of units: starch, cellulose, glycogen.
• Reducing sugars reduce Fehling's solution and Tollens' reagent. All monosaccharides are reducing; among disaccharides, maltose and lactose are reducing but sucrose is non-reducing.

Glucose

Preparation: sucrose boiled with dilute HCl or H₂SO₄ in alcoholic solution gives glucose and fructose in equal amounts. Commercially, starch is hydrolysed by boiling with dilute H₂SO₄ at 393 K under pressure.

Natural glucose is D-(+)-glucose. "D" describes the configuration: in the Fischer projection, the -OH on the lowest chiral carbon (C-5) is on the right, as in D-(+)-glyceraldehyde. "(+)" means it is dextrorotatory. The two symbols are independent of each other.

Cyclic structure

The open-chain formula could not explain several facts: glucose does not give Schiff's test and does not form the NaHSO₃ addition product; glucose pentaacetate does not react with hydroxylamine, so no free -CHO is present; and glucose exists in two crystalline forms, α (m.p. 419 K) and β (m.p. 423 K). The explanation is that the -OH on C-5 adds to the -CHO group to form a six-membered cyclic hemiacetal.

Ring closure makes C-1 a new chiral centre, so two forms arise, differing only in the configuration at C-1. They are called anomers, and C-1 is the anomeric carbon. The six-membered ring (five C and one O) resembles pyran, so the forms are named α-D-glucopyranose and β-D-glucopyranose.

Fructose

Fructose, C₆H₁₂O₆, is a ketohexose with the keto group at C-2. Natural fructose is D-(−)-fructose (laevorotatory). It forms a five-membered ring by addition of the C-5 -OH to the C-2 carbonyl; the ring resembles furan, so the forms are called α- and β-D-fructofuranose.

Disaccharides and polysaccharides

Two monosaccharide units are joined by a glycosidic linkage through an oxygen atom, with loss of a water molecule.

Proteins

Amino acids

Proteins are built from α-amino acids, which have an amino group and a carboxyl group on the same carbon: RCH(NH₂)COOH. About twenty of them occur in proteins. Amino acids that the body can make are non-essential; those that must come from the diet are essential (for example valine, leucine, isoleucine, lysine, threonine, methionine, phenylalanine and tryptophan).

• They are classed as neutral, acidic or basic depending on the relative number of amino and carboxyl groups.
• In aqueous solution the -COOH loses a proton and the -NH₂ gains one, giving a dipolar ion, the zwitterion (H₃N⁺-CHR-COO⁻). Amino acids are therefore amphoteric, and they are colourless crystalline solids with high melting points, behaving more like salts than like typical amines or acids.
• Except glycine (R = H), all naturally occurring α-amino acids are optically active, and most have the L configuration.

Peptide bond

The -COOH of one amino acid and the -NH₂ of another combine with loss of water to form an amide link, -CO-NH-, called the peptide bond.

Two amino acids give a dipeptide, three a tripeptide, and so on; more than ten give a polypeptide. A polypeptide with more than a hundred amino acid residues and molecular mass above 10,000 u is called a protein.

Worked example: How many different tripeptides can be made from glycine (Gly), alanine (Ala) and phenylalanine (Phe) if each is used exactly once? How many peptide bonds does each contain?
Solution: the three residues can be arranged in 3 × 2 × 1 = 6 sequences: Gly-Ala-Phe, Gly-Phe-Ala, Ala-Gly-Phe, Ala-Phe-Gly, Phe-Gly-Ala and Phe-Ala-Gly. They are all different, because each chain has a definite N-terminal and C-terminal end. A tripeptide has 3 − 1 = 2 peptide bonds.

Structure of proteins

• Fibrous proteins have parallel polypeptide chains held by hydrogen and disulphide bonds; they are generally insoluble in water (keratin in hair, wool and silk; myosin in muscle). Globular proteins have chains coiled into spherical shapes and are usually water soluble (insulin, albumins).
• Primary structure: the sequence of amino acids. Any change in the sequence gives a different protein.
• Secondary structure: the shape of the chain. In the α-helix, the chain forms a right-handed coil with each -NH group hydrogen bonded to a C=O group of an adjacent turn. In the β-pleated sheet, chains lie side by side, almost fully stretched, and are held by hydrogen bonds between chains.
• Tertiary structure: further folding of the chain, giving the overall fibrous or globular shape. It is held by hydrogen bonds, disulphide links, van der Waals forces and electrostatic attractions.
• Quaternary structure: the arrangement of two or more polypeptide subunits relative to each other, as in haemoglobin.

Denaturation: a change in temperature or pH disturbs the hydrogen bonds, so the globules unfold and helices uncoil. Secondary and tertiary structures are lost and the protein loses its biological activity, but the primary structure is unchanged. Examples: coagulation of egg white on boiling and curdling of milk by lactic acid produced by bacteria.

Enzymes

Enzymes are biological catalysts, and almost all of them are globular proteins. Each is highly specific for a particular reaction and substrate. They are usually named after the substrate or reaction with the ending -ase: maltase converts maltose into glucose; oxidoreductases catalyse oxidation of one substrate with reduction of another. Like other catalysts, enzymes work by lowering the activation energy of the reaction.

Vitamins

Vitamins are organic compounds needed in small amounts in the diet for normal growth and health. Fat soluble vitamins (A, D, E, K) are stored in the liver and adipose tissue. Water soluble vitamins (B group and C) must be supplied regularly, since they are readily excreted in urine and cannot be stored, vitamin B₁₂ being the exception.

Nucleic acids

Nucleic acids, DNA (deoxyribonucleic acid) and RNA (ribonucleic acid), are long polymers of nucleotides. A nucleotide has three parts: a nitrogenous base, a pentose sugar and a phosphate group. Base plus sugar alone is a nucleoside.

Nucleotides are joined by phosphodiester linkages between the 5′ and 3′ carbons of neighbouring sugars. In the double helix, the two strands are held by hydrogen bonds between specific base pairs: adenine pairs with thymine (two hydrogen bonds) and guanine with cytosine (three hydrogen bonds).

Hormones (general idea)

Hormones are chemical messengers made by endocrine glands and carried by the blood to target tissues. Some are steroids (oestrogens and androgens), some are polypeptides (insulin, endorphins) and some are amino acid derivatives (adrenaline, noradrenaline, thyroxine). Insulin and glucagon together keep blood glucose within a narrow range.

Common mistakes: (1) Reading "D" as dextrorotatory. D is configuration; (+) is rotation, and D-fructose is laevorotatory. (2) Calling sucrose a reducing sugar. (3) Mixing up the linkages: amylose and maltose are α(1→4), cellulose is β(1→4), and amylopectin and glycogen also have α(1→6) branches. (4) Saying denaturation breaks peptide bonds; the primary structure survives. (5) Putting thymine in RNA or uracil in DNA.

JEE and NEET focus

• Classification of carbohydrates and which sugars are reducing.
• Reactions that establish the open-chain structure of glucose, and the facts that need the cyclic structure; anomers and Haworth forms.
• Composition and linkages of sucrose, maltose, lactose, starch, cellulose and glycogen; invert sugar.
• Zwitterions, essential amino acids, the peptide bond, levels of protein structure and denaturation.
• Vitamin deficiency diseases; DNA vs RNA sugars and bases, base pairing and phosphodiester links.

Practice questions