Biomolecules — NEET Notes

Carbohydrates — classification

Carbohydrates are optically active polyhydroxy aldehydes or ketones, or compounds that yield such units on hydrolysis. The old name "hydrate of carbon" comes from the general formula C_x(H₂O)_y — glucose fits as C₆(H₂O)₆ — but the definition by functional group is what matters chemically, because acetic acid fits the formula and is not a carbohydrate, while rhamnose is a carbohydrate that does not. Carbohydrates are also called saccharides, from the Greek sakcharon for sugar.

NCERT classifies carbohydrates along two independent axes. The first is by behaviour on hydrolysis: monosaccharides cannot be hydrolysed further; oligosaccharides yield two to ten monosaccharides (disaccharides being the most common); polysaccharides yield a large number. The second is by reducing power: reducing sugars reduce Fehling's solution and Tollens' reagent, and all monosaccharides (aldose or ketose) plus most disaccharides qualify; non-reducing sugars like sucrose and trehalose cannot, because their anomeric carbons are locked into a glycosidic bond. Monosaccharides are sub-classified by the carbonyl type (aldose for –CHO, ketose for >C=O) and by carbon count: triose (3), tetrose (4), pentose (5), hexose (6).

Monosaccharides — glucose & fructose

Glucose — the master sugar

Glucose (C₆H₁₂O₆) is an aldohexose, also called dextrose, and is probably the most abundant organic compound on Earth. Commercially it is obtained either from sucrose (boiling with dilute HCl in alcoholic solution gives equimolar glucose and fructose) or from starch (hydrolysis with dilute H₂SO₄ at 393 K, 2–3 atm). Its open-chain Fischer projection was worked out by Emil Fischer from six pieces of evidence: HI reduction gives n-hexane (straight chain of six C); reaction with hydroxylamine and HCN proves a >C=O group; mild oxidation with bromine water gives gluconic acid (so the carbonyl is an aldehyde); acetylation gives a pentaacetate (five –OH groups, all on different carbons); nitric-acid oxidation gives saccharic acid, a diacid (a primary alcoholic –OH at C6); and the spatial configuration is fixed by correlation with D-glyceraldehyde.

The full name is D-(+)-glucose. The "D" refers to the relative configuration — the –OH on the lowest asymmetric carbon (C5) lies on the right of the Fischer projection, by analogy with D-glyceraldehyde. The "(+)" denotes dextrorotation. The two are independent; D does not imply (+).

The open-chain structure cannot, however, explain everything. Glucose does not give the Schiff's test for aldehydes, does not form a hydrogen-sulphite addition product with NaHSO₃, and shows mutarotation — the optical rotation of a freshly prepared solution drifts from +111° (α-form) or +19° (β-form) to a constant equilibrium value of +52.5°. These observations are explained only by the cyclic hemiacetal form: the –OH at C5 attacks the C1 aldehyde, generating a six-membered pyranose ring with a new stereocentre at C1 (the anomeric carbon). The two possible orientations of the C1 –OH give two anomers — α-D-glucose (–OH down in the Haworth projection) and β-D-glucose (–OH up) — that interconvert in solution through a trace of open-chain form. This interconversion is mutarotation.

Fructose — the ketohexose

Fructose has the same molecular formula as glucose (C₆H₁₂O₆) but is a ketohexose: the carbonyl is at C2 as >C=O, not C1 as –CHO. It belongs to the D-series (lowest asymmetric carbon, C5, has –OH on the right) but is laevorotatory, so its full name is D-(−)-fructose. In solution, fructose exists predominantly as the β-D-fructofuranose ring — a five-membered ring closed when the C5 –OH attacks the C2 keto group. Inside sucrose, fructose is in this furanose form.

Disaccharides — sucrose, lactose, maltose

A disaccharide is the condensation product of two monosaccharides joined by a glycosidic linkage — an oxygen bridge between the anomeric carbon of one sugar and an –OH of the other, with loss of water. The three NEET-relevant disaccharides are sucrose, lactose, and maltose.

Sucrose (table sugar) is α-D-glucopyranose linked α(1→2)β to β-D-fructofuranose. Both anomeric carbons (C1 of glucose, C2 of fructose) are committed to the glycosidic bond, so neither ring can open to expose a free carbonyl. Sucrose is therefore non-reducing. On hydrolysis with dilute acid or with the enzyme invertase, sucrose yields one molecule of glucose and one of fructose — an equimolar mixture called invert sugar. The name comes from the inversion of optical rotation: sucrose is dextrorotatory (+66.5°), but the product mixture is laevorotatory because the strong negative rotation of fructose (−92°) overwhelms the positive rotation of glucose (+52.5°). NEET 2020 asked the specific anomeric forms — α-D-glucose and β-D-fructose.

Lactose (milk sugar) is β-D-galactopyranose linked β(1→4) to D-glucopyranose. The C1 of glucose remains free, so lactose is reducing. Maltose (malt sugar) is two D-glucopyranose units joined by an α(1→4) glycosidic bond, with the C1 of the second glucose free — also reducing. The pattern is clean: if both anomeric carbons are in the glycosidic bond, the disaccharide is non-reducing; if at least one is free, it is reducing.

Polysaccharides — starch, cellulose, glycogen

Polysaccharides are long polymers of monosaccharide units joined by glycosidic bonds. They are not sweet, hence the alternative name non-sugars. The three NEET polysaccharides — starch, cellulose, and glycogen — are all polymers of glucose, but they differ in the type of glycosidic bond and the branching pattern, and those differences decide their function entirely.

Starch is the reserve carbohydrate of plants. It is a mixture of two polymers: amylose, a linear chain of α-D-glucose units joined by α(1→4) glycosidic bonds, water-soluble, accounting for 15–20% of starch; and amylopectin, a branched polymer of α-D-glucose with α(1→4) linkages along the main chain and α(1→6) linkages at the branch points (about one branch every 20–25 residues), water-insoluble, accounting for 80–85%. NEET 2018 asked exactly this difference and the answer was "amylopectin has both 1→4 α-linkage and 1→6 α-linkage".

Cellulose is the structural carbohydrate of plant cell walls — the most abundant organic compound in the biosphere. It is a linear polymer of β-D-glucose units joined by β(1→4) glycosidic bonds. The β-configuration causes successive glucose units to flip 180°, giving a straight, fully extended ribbon. Many ribbons hydrogen-bond side-by-side into microfibrils of tremendous tensile strength. Humans lack β-glucosidase, so we cannot digest cellulose; ruminants house bacteria that can. Glycogen is the animal storage polysaccharide — found chiefly in liver, muscles, and brain. Its structure resembles amylopectin (α(1→4) main chain, α(1→6) branches) but with branches every 8–12 residues, making it more compact than amylopectin and faster to mobilise. When the body needs glucose, enzymes (glycogen phosphorylase) snip glucose units off the many non-reducing ends in parallel.

Amino acids & the zwitterion

The word protein comes from the Greek proteios — "of prime importance" — and proteins are polymers of α-amino acids. An α-amino acid carries an –NH₂ group on the α-carbon (the one bearing the –COOH), and a side chain R that decides the chemistry. About 20 standard α-amino acids occur in natural proteins. By the nature of R, they are classed as acidic (Asp, Glu — extra –COOH), basic (Lys, Arg, His — extra –NH₂), or neutral. NEET 2020 asked you to pick the basic amino acid out of alanine, tyrosine, lysine, and serine — the answer is lysine, because its side chain –(CH₂)₄–NH₂ adds an extra amino group.

By nutritional requirement, amino acids are split into essential (cannot be synthesised by the body; must come from diet — Val, Leu, Ile, Thr, Met, Phe, Trp, Lys, His) and non-essential (the body can synthesise them). Glycine, H₂N–CH₂–COOH, is the simplest amino acid — and the only one whose α-carbon does not have four different substituents. It is therefore the only achiral standard amino acid. Every other amino acid is chiral and naturally occurs in the L-configuration.

Amino acids dissolved in water exist almost entirely as zwitterions — the proton from –COOH migrates to –NH₂, giving a molecule with one positive and one negative centre, electrically neutral overall. NEET 2018 asked which compound can form a zwitterion among aniline, acetanilide, benzoic acid, and glycine; only glycine, because it carries both –NH₂ and –COOH on the same carbon. In strongly acidic solution the zwitterion picks up a proton (–COO⁻ → –COOH) and becomes a cation; in strongly alkaline solution it loses one (–NH₃⁺ → –NH₂) and becomes an anion. The pH at which the molecule exists predominantly as the zwitterion — net charge zero, zero migration in an electric field — is the isoelectric point (pI). The zwitterion structure also explains why amino acids have unusually high melting points and are far more water-soluble than corresponding hydrocarbons of similar mass.

Protein structure — four levels

The peptide bond, –CO–NH–, is the amide linkage that joins amino acids. It forms when the –COOH of one amino acid condenses with the –NH₂ of the next with loss of water. Two amino acids give a dipeptide; three give a tripeptide; long chains are polypeptides; chains of more than about a hundred residues with molecular masses above 10,000 u are called proteins. Insulin is at the small end with 51 amino acids in two chains. NEET 2016 asked the simple question: in a protein molecule the amino acids are linked by — the answer is peptide bonds, not α- or β-glycosidic bonds (those join sugars).

Above the linear sequence, proteins fold into a four-level hierarchy. Each level is stabilised by a distinct set of bonds, and each level controls a distinct aspect of function. Memorise this hierarchy as one block — NEET asks about it almost every other year.

Primary structure is the order of amino acids along the chain — change one residue and you have a different protein (sickle-cell haemoglobin differs from normal haemoglobin by a single Glu → Val substitution at position 6 of the β chain). Secondary structure is the local folding into α-helix or β-sheet, stabilised by hydrogen bonds between the >C=O of one peptide bond and the –NH– of another. Tertiary structure is the overall three-dimensional shape of the single polypeptide, held together by hydrogen bonds, disulphide bridges (–S–S– between two cysteine residues), ionic interactions, and hydrophobic forces; it gives proteins their globular or fibrous appearance. Quaternary structure is the spatial arrangement of two or more polypeptide subunits — haemoglobin is a tetramer of two α and two β chains; insulin's A and B chains, NEET 2016 noted, are held together by disulphide bridges.

Denaturation of proteins

When a protein is exposed to physical or chemical stress — heat, strong acid or alkali, organic solvents, heavy-metal salts, or detergents — the hydrogen bonds and disulphide bridges that hold its higher-order structure collapse. The α-helix uncoils, the globules unfold, and the protein loses its biological activity. The secondary and tertiary structures are destroyed; the primary structure (the peptide sequence) survives. This is denaturation. NEET 2017 asked which statement is not correct — the trap was "denaturation makes the proteins more active". It does the opposite. Once the native fold is gone, an enzyme cannot bind its substrate, an antibody cannot recognise its antigen, haemoglobin cannot bind oxygen.

The everyday examples are familiar. The coagulation of egg-white on boiling is the heat denaturation of ovalbumin — the clear viscous albumen turns into an opaque solid as the unfolded protein chains tangle into an insoluble network. The curdling of milk under acid is the denaturation of casein. Where does the water in the egg go? Trapped inside the tangled denatured-protein meshwork. The coagulated protein is not a different molecule from native ovalbumin — the amino-acid sequence is the same. What changed is the fold.

Enzymes — the biocatalysts

Enzymes are biocatalysts — almost all of them are globular proteins (a few catalytic RNAs exist, called ribozymes). Their names usually end in -ase and are derived either from the substrate (sucrase hydrolyses sucrose, maltase hydrolyses maltose) or from the reaction type (oxidoreductases catalyse oxidation–reduction). Enzymes are remarkable on two counts: they accelerate biochemical reactions by factors of 10⁶–10²⁰ over the uncatalysed rate, and they do so with breathtaking specificity — one enzyme typically acts on one substrate or one bond. NCERT cites the example of sucrose hydrolysis: activation energy is 6.22 kJ/mol uncatalysed, but only 2.15 kJ/mol with sucrase.

The mechanism is described by the lock-and-key model (and its modern refinement, induced fit). The enzyme has an active site whose geometry and chemical environment fit the substrate molecule like a lock fits its key; only the correct substrate enters, and once bound, the enzyme stabilises the transition state and lowers the activation energy. The reaction proceeds, products are released, and the free enzyme is ready for the next cycle. NEET 2022 tested the basic claim that enzymes are biocatalysts that reduce activation energy and are substrate-specific — the wrong option said "enzymes are polysaccharides", a textbook trap because enzymes are proteins, not polysaccharides.

Vitamins — fat- vs water-soluble

Vitamins are small organic compounds that the body cannot synthesise in adequate amounts but needs in tiny quantities for normal physiology. They are obtained from the diet (vitamin D is partly synthesised in skin under sunlight; gut bacteria produce some of the B group and vitamin K). The original name vitamine — Funk, 1912 — meant "vital amine"; the final "e" was dropped when later vitamins turned out not to be amines. Deficiency of each vitamin produces a specific disease, and NEET has been steady on this list.

Vitamins are divided by solubility into two clean groups. Fat-soluble vitamins — A, D, E, K — dissolve in fats and oils, are stored in the liver and adipose tissue, and need not be supplied daily. Water-soluble vitamins — the B-complex (B₁, B₂, B₃, B₅, B₆, B₇, B₉, B₁₂) and vitamin C — must be supplied regularly in the diet because the body cannot store them (except B₁₂, which is stored in the liver). Excess water-soluble vitamins are simply excreted in urine.

Nucleic acids — DNA & RNA

Nucleic acids are the chemical carriers of genetic information. There are two kinds — deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) — both polymers of nucleotides. Every nucleotide is built from three components: a nitrogenous base, a pentose sugar, and a phosphate group. Strip off the phosphate and you have a nucleoside; add it back and you get a nucleotide. NEET 2023 tested this distinction in a statement pair, and the rule to remember is brutally simple.

The nitrogenous bases are of two chemical families. Purines are bicyclic (a six-membered ring fused to a five-membered ring) and include adenine (A) and guanine (G). Pyrimidines are monocyclic (a six-membered ring only) and include cytosine (C), thymine (T), and uracil (U). A and G occur in both DNA and RNA; C occurs in both; T is unique to DNA; U is unique to RNA. The sugar is 2-deoxy-D-ribose in DNA (no –OH at C2 of the ribose) and D-ribose in RNA. NEET 2016 asked precisely this sugar contrast — the answer was "the sugar component in RNA is ribose and in DNA is 2-deoxyribose".

In a nucleic acid, the base is attached to the C1′ of the sugar; the phosphate is attached to the C5′ of the sugar. The polymer runs through 5′ → 3′ phosphodiester bonds — the C3′-OH of one sugar links via a phosphate to the C5′ of the next. The phosphate-sugar backbone is the same along the chain; only the bases vary, and the sequence of bases is the genetic message.

James Watson and Francis Crick, in 1953, proposed that DNA exists as a double helix — two strands wound around a common axis. The strands run antiparallel: one 5′ → 3′, the other 3′ → 5′. The sugar-phosphate backbones are on the outside; the bases point inward and pair up across the helix according to the Watson–Crick rules (A–T, G–C). One full turn of the helix is about 3.4 nm and contains roughly 10 base pairs. Hydrogen bonds between complementary bases give the helix its stability and dictate the precision of replication: when the strands separate, each can act as a template for the synthesis of a new complementary strand. RNA is usually single-stranded, but folds back on itself to form intricate secondary structures — tRNA's cloverleaf, ribosomal RNA's complex three-dimensional fold — through internal A–U and G–C pairing.

RNA exists in three principal forms in the cell. Messenger RNA (mRNA) carries the coded message from DNA to the ribosome; transfer RNA (tRNA) brings the amino acids one by one to the ribosome and reads the message through its anticodon; ribosomal RNA (rRNA) forms the structural and catalytic core of the ribosome itself. Together, the three RNAs translate the genetic message into a protein. The molecular logic of inheritance — DNA → RNA → protein — is the central dogma, and it operates because the chemistry of base-pairing is exact.