Biomolecules

Introduction — Living Chemicals/Biomolecules

All organisms are made up of some chemicals which are called biomolecules. There is wide variety in living organisms — herbivores, carnivores — but all of them are made up of the same chemicals, i.e. the same elements and compounds.

Biomicromolecules and Biomacromolecules

Biomicromolecules: molecular weight 18–800 Dalton. Monomeric substances such as amino acids, simple sugars, nucleotides.

Biomacromolecules: Polymeric, except lipid. Examples: Protein, Carbohydrate, Nucleic acid.

A Comparison of Elements Present (% of weight) — Non-living and Living Matter

Analyse of Living Cell — Acid Soluble Pool & Acid Insoluble Pool

If a living tissue is ground in trichloroacetic acid (TCA) using a mortar and pestle, a thick slurry is obtained. On filtering this slurry through cheesecloth or filter paper, two fractions are separated:

Inorganic Constituents of a Living Organism

Component ions: Sodium, Potassium, Calcium, Magnesium, and Water.

Average Chemical Composition of a Cell

Primary and Secondary Metabolites

Examples of Secondary Metabolites

• Pigments: Carotenoids, Anthocyanins etc.
• Alkaloids: Morphine, Codeine
• Terpenoids: Monoterpenes, Diterpenes etc., Lemon grass oil etc.
• Toxins: Abrin, Ricin
• Lectins: Concanavalin A
• Drugs: Vinblastin, Curcumin etc.
• Others: Rubber, Gums

Carbohydrate

Carbo: Carbon, Hydrate: Hydrate of water.

It is an Aldehyde or Ketone: Glucose, Galactose — Aldo (C:O 1:1, CH-O:H); Fructose — Ketone.

Types of Carbohydrate

• Simple Carbohydrate — Monosaccharide (1 sugar unit): Glucose, Fructose, Galactose
• Oligosaccharide (2 to 10 sugar units): Maltose (G+G), Lactose (G+Galactose), Sucrose (G+F)
• Complex — Polysaccharide (>10 sugar units): Glycogen, Heteropolysaccharide (Peptidoglycan, Hyaluronic acid)

Monosaccharide

Cannot be further hydrolysed. For C3 to C7 carbon atoms: C₃H₆O₃, C₄H₈O₄, C₅H₁₀O₅, C₆H₁₂O₆.

Structure — Open Chain and Ring Forms

Monosaccharides can exist in open chain form as well as ring forms. Glucose forms a six-membered ring (Pyranose ring). Fructose forms a five-membered ring (Furanose ring).

Anomers

The two ring forms which differ in position (configuration) at C1 carbon are called Anomers — α-position and β-position (e.g., α-D-Glucose, β-D-Glucose).

Isomers of Monosaccharide

Molecules with the same molecular formula but different structural form. Epimers — differ only at one position, e.g. Glucose and Galactose, Glucose and Mannose.

Disaccharides

A disaccharide is formed when two monosaccharides are joined together by a glycosidic linkage, with the loss of one water molecule.

Polysaccharides

Macromolecule, present in acid insoluble pool. Tasteless, insoluble in water. Produced by >10 monosaccharides. Linkage — Glycosidic linkage. Left end — non-reducing.

Storage Polysaccharide

• Plant — Starch
• Animal — Glycogen

Structural Polysaccharide

• Polymer of, branched and unbranched.

Starch

Total Starch is divided into two types:

Glycogen

Polymer of α-glucose. Branched structure, Linkage: chain α(1→4), branching α(1→6) after every 9 units. Glycogen is found in animals.

Cellulose

Polymer of β-glucose, unbranched structure, Linkage: β(1→4). 1st most abundant polymer, present in cell wall of plant, algae. Used in wood pulp. Cellulose enzyme is absent in animals — animals cannot release/digest cellulose.

Chitin

Polymer of N-acetylglucosamine. Unbranched structure, Linkage: β(1→4). Most abundant polymer present in arthropod exoskeleton, present in fungal cell wall.

Heteropolysaccharide

• Peptidoglycan: N-acetyl muramic acid + N-acetylglucosamine, present in bacterial cell wall.
• Hyaluronic acid: glucuronic acid + N-acetylglucosamine, present in connective tissue.

Amino Acids

Monomer unit of Protein. Micromolecules, present in acid soluble pool.

Structure

A central Carbon (α-Carbon) is attached to: Amino group (NH₂), Carboxyl group (COOH), Alkyl group (R), and a Hydrogen atom.

Property of Amino Acids

• More than 300 amino acids are present in nature; only 20 amino acids participate in protein synthesis.
• All amino acids except Glycine are optically active (chiral).
• Proline has an Imino (NH) group instead of an amino group.
• Tyrosine, Phenylalanine and Tryptophan absorb UV light.

Zwitterionic Form of Amino Acid

A particular property of amino acids is the ionizable nature of -NH₂ and -COOH groups. Hence in solutions of different pH, the structure of amino acids changes:

• At Acidic pH (pH = pK1): amino acid exists as NH₃⁺ — C — COOH (positive form)
• At Isoelectric point (pI): Zwitterion — NH₃⁺ — C — COO⁻ (net neutral form)
• At Basic pH: NH₂ — C — COO⁻ (negative form)

Essential and Non-Essential Amino Acids

Classification of Amino Acids

• Acidic amino acids (-COOH > -NH₂): e.g. Aspartic acid, Glutamic acid
• Basic amino acids (-NH₂ > -COOH): e.g. Arginine, Histidine
• Neutral amino acids (-NH₂ = -COOH): e.g. Alanine, Valine, Leucine
• Sulphur-containing amino acids: Cysteine, Cystine, Methionine
• Aromatic amino acids: Phenylalanine, Tyrosine, Tryptophan
• Hydroxy amino acids: Serine, Threonine, Tyrosine

Derivatives of Amino Acids

• Tyrosine: Dopamine, Epinephrine, Thyroxin (iodinated form of Tyrosine)
• Tryptophan: Auxin, Vitamin B3 (Niacin)
• Histidine: Histamine
• Glutamic acid: GABA
• Glycine: Heme of haemoglobin

Proteins

Proteins are polypeptides — amino acids linked by peptide bonds are linear chains. The protein chain has an N-terminus (NH₂) and a C-terminus (COOH).

Peptide Bond and Bonding Angle of Protein

Peptide bond is a covalent bond. The bonding angle φ (phi) = ±180° and ψ (psi) = ±180°.

Molecular Weight of Protein

Each protein is a polymer of amino acids. As there are 20 types of amino acid, the average molecular weight of an amino acid (after loss of water during peptide bond formation) is taken as 128 (Amino acid = 128 × n — n × 18 for water loss, where n = number of amino acids, AA — H₂O = 110 average residue weight).

Structure of Protein — Four Levels

While organic chemists always write a structural formula for a molecule (e.g. benzene, naphthalene) representing a two-dimensional/three-dimensional view, biologists describe the structure of protein at four levels:

Bonds Stabilising Protein Structure

• H-bond: stable, non-covalent interaction (β-pleated structure)
• Disulphide bond: covalent bond, covalent interaction
• Vanderwaal forces and Electrostatic interaction: non-covalent interaction

Denaturation of Protein

Denaturation — Breakdown of non-covalent interaction and covalent bonds (disulphide bond) but not the peptide bond, resulting in loss of biological activity (3D structure).

Factors Responsible for Denaturation of Protein

• Increase in Temperature — breakdown of H-bond, Vanderwaal forces.
• Change in pH (Hydrogen ion concentration) — breakdown of H-bond.
• Strong acid and base.
• Organic solvent and reducing agent — breakdown of disulphide bond, oxidising interaction.

Functions of Proteins (Examples)

Lipids (Fat)

Water insoluble, but soluble in organic solvents. Molecular weight < 800 Dalton. Present in acid insoluble pool, not a polymer. But part of macromolecule pool.

Structure

It is formed by esterification of Glycerol (Glycerol = Propane with 3 -OH groups) with Fatty acids:

Lipid = Glycerol + Fatty acids

Types of Fatty Acids

Classification of Lipids

• Simple Lipids: Esters of fatty acid & Glycerol. Waxes — Esters of long chain fatty acid & long chain alcohol.
• Compound Lipids: Esters of fatty acids & Alcohol, contain other groups also:
  • Phospholipid — present in membrane
  • Glycolipid (Glycosphingolipid) — present in myelin sheath of neurons
  • Lipoprotein — combination of Lipid + Protein, e.g. Chylomicron, membrane receptor
  • Chromolipid — pigment containing lipid, e.g. Carotenoid (Pro-Vitamin A)
• Derived Lipids: Composed of hydrocarbon rings and a chain. e.g. Cholesterol — most abundant steroid in animals. Cholesterol has a fat-like Penta + Hexa ring (Hexa Ring + 1 Pentagonal ring) with H-C chain. Fatty acids are absent in Cholesterol. Cholesterol is precursor of most steroidal hormones — Adrenal Cortex, Sex hormone, Triglycerides.

Enzymes

Mostly enzymes are Proteins (Biocatalyst). Globular, with active site/binding sites/crevices. Ribozyme — RNA with tertiary structure and catalytic activity (e.g. RNase P, an endonuclease).

Difference between Biocatalyst and Inorganic Catalyst

Physical and Chemical Change

• Physical Change: Change in shape without breakdown of bond, e.g. change in state of matter (Vapour).
• Chemical Change: Breakdown and transformation of bond.

Rate of Chemical/Physical Process

Factors which influence the rate: Temperature, pH, substrate concentration, presence of inhibitor.

How do Enzymes Bring About Such a High Rate of Conversion?

By reducing the Activation Energy required for the initiation of a chemical reaction.

The reaction passes through a Transitional state. Activation energy without enzyme is higher than activation energy in presence of enzyme. The reaction shows a Free Energy Change (ΔG) — exothermic nature, releasing energy. Substrate (e.g. Sucrose) binds at the Active Site of enzyme, forming ES complex, which converts to E + Products (Glucose + Fructose).

Factors Affecting Enzyme Activity

(i) Temperature

Optimum temperature of enzyme = 37°C. Below and above optimum, Vmax decreases (inactivation). A rise of 10°C in temperature increases Vmax (up to optimum, after which it decreases).

(ii) pH

All enzymes are protein (polymer of amino acid). e.g. Salivary Juice (Salivary Amylase) — optimum pH ≈ 6.8; Intestinal Juice — optimum pH ≈ 7.0. Velocity of reaction varies with pH — there is an optimum pH at which Vmax is highest.

(iii) Substrate Concentration

If substrate concentration increases → velocity of reaction increases. But after 100% saturation of enzyme, if substrate concentration increases further, Vmax remains constant. Km = Concentration of substrate at which the reaction rate is half of Vmax.

(iv) Inhibitors

Classification and Nomenclature of Enzymes

Enzymes are divided into 6 classes, each with 4–13 subclasses. Each enzyme is given a four-digit number (Class.Subclass.Sub-subclass.Individual enzyme number).

Co-factors

The protein part of the conjugate enzyme present in active form is called the holoenzyme; the protein part without the cofactor is the inactive apoenzyme.

Dynamic State of Body Constituents — Concept of Metabolism

All living organisms maintain a steady-state concentration of biomolecules — in terms of mol/cell or mol/litre. One of the greatest discoveries ever made was that all these biomolecules are in a turnover, i.e., they are constantly being made and broken down.

Turnover

Turnover number of an enzyme — number of substrate molecules transformed per minute per enzyme molecule. Maximum turnover number → Carbonic Anhydrase.

Flow of metabolites through a metabolic pathway has a definite rate and direction, like automobile traffic. This is called the dynamic state.

Anabolic and Catabolic Pathways — Basis for Living

ATP — Adenosine Triphosphate

The most important form of energy currency in a living system is the bond energy in a chemical called Adenosine Triphosphate (ATP). ATP is composed of: Adenine + Ribose + Triphosphate.

Practice Questions