Biomolecules: Carbohydrates, Proteins, and Lipids

Biomolecules are the organic compounds that constitute all living organisms. Understanding their structures, classifications, and functions is fundamental to health sciences because virtually every drug, every disease process, and every metabolic pathway in the human body involves biomolecules. For the HAAD examination, questions on carbohydrates, proteins, and lipids are particularly common because these molecules are central to human biochemistry, nutrition, pharmacology, and clinical chemistry. This chapter provides a comprehensive overview of the three major classes of biomolecules: carbohydrates, proteins, and lipids.

Carbohydrates

Carbohydrates are polyhydroxy aldehydes or ketones, or compounds that yield these upon hydrolysis. They are the body’s primary source of energy (providing 4 kcal/gram) and are also structural components of cells (e.g., cellulose in plants, chitin in fungi and arthropods).

Classification

Monosaccharides are the simplest carbohydrates — single sugar units that cannot be hydrolyzed into smaller sugars. They are classified by:

• Number of carbon atoms: Trioses (3C), tetroses (4C), pentoses (5C), hexoses (6C), heptoses (7C)
• Presence of aldehyde or ketone group: Aldoses (aldehyde sugar, e.g., glucose) and ketoses (ketone sugar, e.g., fructose)

Key monosaccharides:

Name	Type	Formula	Importance
Glucose	Aldohexose	C₆H₁₂O₆	Blood sugar; primary energy source
Fructose	Ketohexose	C₆H₁₂O₆	Fruit sugar; converted to glucose in liver
Galactose	Aldohexose	C₆H₁₂O₆	Component of lactose
Ribose	Aldopentose	C₅H₁₀O₅	Component of RNA
Deoxyribose	Aldopentose	C₅H₁₀O₄	Component of DNA (missing O at C2)

Glucose (also called dextrose or blood sugar) is the most important carbohydrate in human metabolism. It has four chiral centers (C2, C3, C4, C5), giving 2⁴ = 16 possible stereoisomers. The naturally occurring D-glucose (specifically β-D-glucopyranose in its cyclic form) is the biologically active form.

Cyclic Structure of Monosaccharides

Monosaccharides with five or six carbons exist predominantly in cyclic form — the carbonyl carbon (C1 in aldoses, C2 in ketoses) reacts with an –OH group on another carbon to form a hemiacetal (in aldoses) or hemiketal (in ketoses), creating a ring.

In glucose, the ring closes between C1 and C5 to form a six-membered pyranose ring (named after pyran, a six-membered oxygen-containing heterocycle). Two anomers are possible:

• α-D-glucose: The –OH on C1 is on the opposite side of the ring from the –CH₂OH group at C6 (down)
• β-D-glucose: The –OH on C1 is on the same side as the –CH₂OH group (up)

The α form predominates in the solid state; both forms exist in equilibrium in solution (mutarotation).

Disaccharides

Disaccharides consist of two monosaccharide units joined by a glycosidic linkage (an oxygen bridge between the two sugar units).

Key disaccharides:

Disaccharide	Composition	Glycosidic Linkage	Occurrence
Maltose	Glucose + Glucose	α(1→4)	Germinating grains
Sucrose	Glucose + Fructose	α(1→2)	Table sugar; cane sugar
Lactose	Glucose + Galactose	β(1→4)	Milk (5% in human milk, 4.7% in cow’s milk)
Cellobiose	Glucose + Glucose	β(1→4)	Product of cellulose digestion

Lactose intolerance occurs when the enzyme lactase (found in the brush border of the small intestine) is deficient — undigested lactose passes to the colon where bacterial fermentation produces gases (H₂, CO₂, CH₄) and short-chain fatty acids, causing bloating, flatulence, and diarrhea.

Polysaccharides

Starch is the energy storage polysaccharide in plants, composed of:

• Amylose: Linear chain of α(1→4)-linked glucose (20–30%); forms a helical structure
• Amylopectin: Branched chain with α(1→4) backbone and α(1→6) branch points (70–80%)

Glycogen is the energy storage polysaccharide in animals, analogous to amylopectin but with more frequent α(1→6) branch points. It is stored in the liver (for blood glucose maintenance) and in skeletal muscle (for local energy use during exercise). Glycogen breakdown (glycogenolysis) is stimulated by glucagon and epinephrine.

Cellulose is a linear polymer of β(1→4)-linked glucose. Humans lack the enzyme cellulase and cannot digest cellulose. Ruminant animals (cows, sheep) have symbiotic bacteria in their rumen that produce cellulase, allowing them to digest grass. The β(1→4) linkages in cellulose form straight chains that pack into rigid microfibrils — this gives plant cell walls their structural strength.

Chitin is a linear polymer of N-acetylglucosamine (GlcNAc), forming the exoskeletons of crustaceans, insects, and the cell walls of fungi.

Tests for Carbohydrates

• Molisch test: General test for carbohydrates — violet ring at interface with α-naphthol and H₂SO₄
• Benedict’s/Fehling’s test: Reducing sugars give brick-red Cu₂O precipitate with hot alkaline copper tartrate
• Iodine test: Starch gives a blue-black color with iodine (amylose helix complexes with iodine)
• Osazone test: Reducing sugars form characteristic crystalline osazones with phenylhydrazine (glucose osazone melts at 204°C; fructose osazone melts at 205°C; maltose osazone melts at 206°C)

Proteins

Proteins are polymers of amino acids linked by peptide bonds (amide linkages). They are the most structurally and functionally diverse class of biomolecules, serving as enzymes, structural components, hormones, antibodies, transport molecules, and contractile elements.

Amino Acids

Amino acids have the general structure: H₂N–CH(R)–COOH, with an amino group (–NH₂), a carboxyl group (–COOH), a hydrogen atom, and a variable R group (the side chain) all attached to the α-carbon.

There are 20 standard amino acids encoded by the genetic code. They are classified by the properties of their side chains:

Nonpolar (hydrophobic) amino acids: Glycine (H), Alanine (CH₃), Valine (isopropyl), Leucine (isobutyl), Isoleucine (sec-butyl), Methionine (sulfur-containing thioether), Phenylalanine (aromatic benzyl), Tryptophan (indole), Proline (secondary amine, causes kinks in helices)

Polar uncharged amino acids: Serine (–CH₂OH), Threonine (–CH(OH)CH₃), Cysteine (–CH₂SH, forms disulfide bonds), Tyrosine (phenol), Asparagine (–CH₂–CONH₂), Glutamine (–CH₂CH₂–CONH₂)

Acidic amino acids: Aspartic acid (–CH₂–COOH, pKa ≈ 3.9), Glutamic acid (–CH₂CH₂–COOH, pKa ≈ 4.3)

Basic amino acids: Lysine (–CH₂CH₂CH₂CH₂–NH₂, pKa ≈ 10.5), Arginine (guanidinium, pKa ≈ 12.5), Histidine (imidazole, pKa ≈ 6.0 — the only amino acid with a side chain that is partially protonated at physiological pH 7.4)

Peptide Bond Formation

When two amino acids join, the carboxyl group of one reacts with the amino group of the other, eliminating water (a condensation/dehydration reaction) to form a peptide bond: H₂N–CH(R₁)–COOH + H₂N–CH(R₂)–COOH → H₂N–CH(R₁)–CO–NH–CH(R₂)–COOH + H₂O

A dipeptide has two amino acids and one peptide bond. A tripeptide has three amino acids and two peptide bonds. A polypeptide has many amino acids. A protein is a functional polypeptide (typically >50 amino acids).

The sequence of amino acids in a protein is its primary structure. This is determined by the DNA sequence of the gene encoding that protein. A change in even one amino acid (a point mutation) can dramatically affect protein function — for example, sickle cell anemia is caused by a single amino acid substitution (glutamic acid → valine at position 6 of the β-globin chain).

Protein Structure

Primary structure: Linear sequence of amino acids, linked by peptide bonds.

Secondary structure: Local spatial arrangements stabilized by hydrogen bonds between peptide groups:

• α-helix: Right-handed helix; H-bond from C=O of residue n to N–H of residue n+4. Found in many globular proteins and in keratin (hair, nails).
• β-sheet (pleated sheet): Extended chains hydrogen-bonded to each other. Can be parallel (same direction) or antiparallel (opposite direction). Found in silk fibroin and in many globular proteins.

Tertiary structure: The overall 3D shape of a single polypeptide chain, stabilized by interactions between side chains: hydrophobic interactions, hydrogen bonds, ionic bonds (salt bridges), van der Waals forces, and disulfide bridges (covalent bonds between cysteine –SH groups, oxidized to –S–S–).

Quaternary structure: The association of two or more polypeptide chains (subunits) to form a functional protein. Hemoglobin (α₂β₂ tetramer) is an example of quaternary structure.

Classification of Proteins

By shape:

• Fibrous proteins: Long, rod-like, insoluble in water — e.g., keratin (hair, nails), collagen (connective tissue), myosin and actin (muscle)
• Globular proteins: Compact, spherical, generally soluble in water — e.g., enzymes, hemoglobin, antibodies

By composition:

• Simple proteins: Yield only amino acids on hydrolysis — e.g., albumin, globulin, histone
• Conjugated proteins: Contain a non-protein prosthetic group:
  • Glycoproteins (carbohydrate prosthetic group): antibodies, hormones (e.g., erythropoietin)
  • Lipoproteins (lipid prosthetic group): chylomicrons, LDL, HDL — transport fats in blood
  • Nucleoproteins (nucleic acid prosthetic group): ribosomes
  • Chromoproteins (pigment prosthetic group): hemoglobin (heme + globin)
  • Metalloproteins (metal ion prosthetic group): many enzymes

Lipids

Lipids are a diverse group of hydrophobic biological molecules that are soluble in non-polar organic solvents (chloroform, methanol, ether) but insoluble in water. They serve as energy storage (fats), structural components of cell membranes (phospholipids and cholesterol), signaling molecules (steroid hormones, eicosanoids), and vitamins (A, D, E, K — all fat-soluble).

Fatty Acids

Fatty acids are long-chain carboxylic acids (typically C12–C24) with a hydrophobic hydrocarbon chain and a hydrophilic carboxyl group. They are usually esterified in triglycerides but exist free in the blood bound to albumin.

Saturated fatty acids have no C=C double bonds (e.g., stearic acid, C₁₈H₃₆O₂ — found in animal fats). They pack tightly → higher melting points → solid at room temperature.

Unsaturated fatty acids have one or more C=C double bonds:

• Monounsaturated (MUFA): One double bond (e.g., oleic acid, C₁₈H₃₄O₂ — found in olive oil)
• Polyunsaturated (PUFA): Multiple double bonds (e.g., linoleic acid, α-linolenic acid — omega-3 and omega-6 fatty acids)

Trans fats are unsaturated fatty acids with trans double bonds (produced by partial hydrogenation of vegetable oils). They are associated with increased LDL cholesterol and cardiovascular disease risk.

Triglycerides (Triacylglycerols)

Triglycerides are triesters of glycerol (propane-1,2,3-triol) and three fatty acids:

• Saturated triglycerides (e.g., from animal fat): Higher melting point → solid at room temperature
• Unsaturated triglycerides (e.g., from vegetable oils): Lower melting point → liquid at room temperature

Triglycerides are the body’s primary energy storage form. Stored in adipose tissue, they yield approximately 9 kcal/gram (more than twice the energy per gram of carbohydrates or proteins).

Phospholipids

Phospholipids are the principal structural components of cell membranes. They have a glycerol backbone esterified to two fatty acids (forming the hydrophobic tail) and a phosphate group esterified to a hydrophilic head group (like choline, serine, ethanolamine, or inositol).

Lecithin (phosphatidylcholine) is the most abundant phospholipid in cell membranes and is also an important emulsifying agent in the bile (helping to solubilize dietary fats in the small intestine).

The phospholipid bilayer forms the basic structure of all cell membranes, with the hydrophobic tails facing inward and the hydrophilic heads facing outward on both sides.

Steroids

Steroids have a characteristic four-ring core structure (three six-membered rings and one five-membered ring) and include:

• Cholesterol: The most abundant steroid in animal cell membranes; precursor to all other steroid hormones, bile acids, and vitamin D. LDL cholesterol (“bad cholesterol”) deposits cholesterol in arterial walls; HDL cholesterol (“good cholesterol”) removes it.
• Bile acids (cholic acid, chenodeoxycholic acid): Emulsify dietary fats in the small intestine.
• Steroid hormones: Cortisol (glucocorticoid), aldosterone (mineralocorticoid), testosterone and estrogen (sex steroids), calcitriol (active form of vitamin D).
• Vitamin D: A steroid hormone involved in calcium homeostasis.

⚡ Exam tip: For carbohydrates: remember the distinction between α and β linkages (α: O below the ring at the anomeric carbon; β: O above). Starch = α(1→4) amylose + α(1→4)/(1→6) amylopectin. Cellulose = β(1→4) glucose (humans can’t digest it). For proteins: primary structure = amino acid sequence; secondary = α-helix and β-sheet; tertiary = overall 3D shape; quaternary = subunit assembly. For lipids: triglycerides are energy storage; phospholipids are membrane components; cholesterol is the precursor to steroid hormones.

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