Biological Molecules
Living matter is built from a small set of recurring molecular families: water, carbohydrates, lipids, proteins, and nucleic acids. The AAMC MCAT content outline expects you to recognize their monomers, polymers, bonds, and biological roles. This is one of the most heavily tested areas — a high-yield area for the Bio/Biochem section.
Biological Importance of Water
Water (H2O) makes up 65-75% of cellular mass and is the medium of every metabolic reaction. Its unique properties arise from polarity and hydrogen bonding between molecules.
- Polarity
- Oxygen is more electronegative than hydrogen, giving water a partial negative pole on O and partial positive poles on H.
- Hydrogen bond
- Weak electrostatic attraction (~5 kcal/mol) between the δ+ H of one water molecule and the δ− O of another.
- Specific heat capacity
- Water requires 1 cal/g/°C — very high — allowing organisms to buffer temperature changes.
- Heat of vaporization
- 540 cal/g — sweating dissipates large amounts of body heat with little water loss.
- Universal solvent
- Polar molecules and ions dissolve readily, enabling transport, digestion, and metabolism.
- Cohesion & adhesion
- Cohesion drives capillary action in xylem; surface tension supports small organisms walking on water.
Biological Molecules — Overview
Biomolecules are classified by structure and function. Most large biomolecules are polymers built from repeating monomers by condensation (dehydration synthesis), and broken down by hydrolysis.
- Carbohydrates — monomer = monosaccharide; main polymer = polysaccharide.
- Lipids — not strictly polymers; built from glycerol + fatty acids.
- Proteins — monomer = amino acid; polymer = polypeptide.
- Nucleic acids — monomer = nucleotide; polymer = DNA or RNA.
Trace and macro elements: C, H, O, N, P, S form ~99% of biomass. Trace minerals (Fe, Mg, Ca, Zn, Cu, I, etc.) are essential cofactors and structural components.
Carbohydrates
Carbohydrates have the general formula (CH2O)n. They serve as the cell's primary fuel, short-term energy store, and structural element.
Single sugar units (3-7 carbons). Examples: glucose, fructose, galactose (all hexoses, C6H12O6); ribose, deoxyribose (pentoses). Reducing sugars (Benedict's positive). Glucose is the universal cellular fuel.
Two monosaccharides joined by a glycosidic bond (formed by condensation, broken by hydrolysis).
- Maltose = glucose + glucose
- Sucrose = glucose + fructose (table sugar; non-reducing)
- Lactose = glucose + galactose (milk sugar)
Long polymers of monosaccharides.
- Starch — plant storage; amylose (linear, α-1,4) + amylopectin (branched).
- Glycogen — animal storage in liver and muscle; highly branched.
- Cellulose — structural in plant cell walls; β-1,4 bonds; humans cannot digest it.
- Chitin — in fungal cell walls and arthropod exoskeletons; contains nitrogen.
Conjugated Molecules
Conjugated molecules are hybrid biomolecules in which a carbohydrate, lipid, or other group is covalently attached to another biomolecule.
- Glycoproteins
- Protein + carbohydrate. Examples: mucins, ABO blood group antigens, antibodies, hormones (FSH, LH, hCG).
- Glycolipids
- Lipid + carbohydrate. Found on the outer leaflet of plasma membrane — cell-cell recognition.
- Lipoproteins
- Lipid + protein complexes that transport cholesterol and triglycerides in blood (HDL, LDL, VLDL, chylomicrons).
- Nucleoproteins
- Nucleic acid + protein, e.g., chromatin (DNA + histones), ribosomes (rRNA + ribosomal proteins).
- Phosphoproteins
- Proteins with phosphate group attached, e.g., casein in milk.
Lipids
Lipids are a heterogeneous group of nonpolar, hydrophobic biomolecules. They store ~9 kcal/g (more than twice the energy density of carbohydrates) and form biological membranes.
One glycerol + three fatty acids joined by ester bonds. Saturated fatty acids (no C=C) are solid at room temperature (animal fats). Unsaturated fatty acids contain C=C double bonds and are liquid (vegetable oils). The body cannot synthesize essential fatty acids (linoleic, linolenic, arachidonic). Cis double bonds put a kink in the chain (lowering the melting point); trans fats are straight and behave like saturated fats.
Glycerol + 2 fatty acids + phosphate group (and usually a head group such as choline). Amphipathic — hydrophilic head, hydrophobic tails. Form the lipid bilayer of all biological membranes.
Four-fused-ring backbone (three 6-carbon + one 5-carbon ring). Examples: cholesterol (membrane fluidity, precursor of steroid hormones), testosterone, estrogen, progesterone, cortisol, aldosterone, vitamin D, bile salts.
Esters of long-chain fatty acids with long-chain alcohols. Waterproof coatings on leaves (cuticle), feathers, fur, and the human ear canal (cerumen).
Proteins
Proteins are polymers of 20 standard amino acids joined by peptide bonds. They are the workhorses of the cell — enzymes, structural fibers, transporters, hormones, antibodies, contractile fibers, and receptors.
Amino acids and the peptide bond
Each amino acid has a central α-carbon bonded to: (1) an amino group (—NH2), (2) a carboxyl group (—COOH), (3) an H, and (4) a variable R side chain that defines its chemistry. In solution near physiological pH, amino acids exist as zwitterions (—NH3+ and —COO− simultaneously); the pH at which the net charge is zero is the isoelectric point (pI). All standard amino acids except glycine are chiral, and proteins use the L-form.
A peptide bond is an amide linkage formed by condensation between the —COOH of one amino acid and the —NH2 of the next (releasing H2O). Because of resonance the C—N bond has partial double-bond character, making the peptide unit rigid and planar (usually trans) — this constrains how the backbone can fold. A chain has directionality: a free amino group at the N-terminus and a free carboxyl at the C-terminus.
The MCAT expects you to sort the 20 amino acids by the chemistry of their R group:
- Nonpolar / hydrophobic — glycine, alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan. Bury in the protein core; proline kinks the backbone.
- Polar uncharged — serine, threonine, cysteine, tyrosine, asparagine, glutamine. Form hydrogen bonds; cysteine's —SH makes disulfide bridges.
- Acidic (negative at pH 7) — aspartate and glutamate (—COO− side chains).
- Basic (positive at pH 7) — lysine, arginine, and histidine (histidine's pKa ≈ 6 makes it a common catalytic residue and buffer).
Nine are essential (must come from the diet): phenylalanine, valine, threonine, tryptophan, isoleucine, methionine, histidine, leucine, lysine ("PVT TIM HaLL").
- Primary — linear amino acid sequence held by peptide bonds.
- Secondary — local folding into α-helix or β-pleated sheet held by hydrogen bonds.
- Tertiary — overall 3D shape stabilized by hydrogen, ionic, hydrophobic, and disulfide bonds (between cysteine residues).
- Quaternary — assembly of >1 polypeptide subunits, e.g., hemoglobin (2α + 2β).
Denaturation — loss of secondary, tertiary, or quaternary structure due to heat, extreme pH, or chemicals. The primary sequence (covalent peptide bonds) remains intact, but the 3D shape — and therefore biological activity — is lost. Chaperone proteins help other polypeptides fold correctly; misfolding underlies diseases such as Alzheimer's and prion disease.
Enzymes
Most enzymes are proteins (a few are catalytic RNAs, or ribozymes) that act as biological catalysts. They speed reactions by lowering the activation energy (Ea), without being consumed and without changing the reaction's overall ΔG or equilibrium position — only the rate.
The active site is the pocket where substrate binds. The older lock-and-key model treats it as a rigid complement; the more accurate induced-fit model has the active site change shape to grip the substrate. Enzymes are highly specific and are sensitive to temperature and pH (each has an optimum; extremes denature the enzyme).
Many enzymes need a non-protein helper. Cofactors are inorganic ions (Fe2+, Mg2+, Zn2+); coenzymes are small organic molecules, often derived from vitamins (e.g., NAD+ from niacin, FAD from riboflavin, coenzyme A from pantothenate). An enzyme without its cofactor is an inactive apoenzyme; the complete, active form is a holoenzyme.
Ribonucleic Acid (RNA)
RNA is a single-stranded polymer of ribonucleotides. Each nucleotide consists of a ribose sugar, a phosphate, and a nitrogenous base — adenine, guanine, cytosine, or uracil (replacing thymine). RNA mediates the flow of genetic information from DNA to protein.
| Property | mRNA | tRNA | rRNA |
|---|---|---|---|
| Full name | Messenger RNA | Transfer RNA | Ribosomal RNA |
| Function | Carries the genetic code from DNA to ribosome | Brings amino acids to the ribosome | Structural & catalytic component of the ribosome |
| Shape | Linear, single-stranded | Clover-leaf (2D); inverted-L (3D) | Folded, complex 3D structure |
| Key feature | Read in codons of 3 bases | Has an anticodon; amino acid attached at 3′ CCA end | Forms peptide-bond active site (peptidyl transferase) |
| Approx. abundance | ~5% | ~15% | ~80% (most abundant) |
| Size | Variable (hundreds–thousands of nt) | ~75–90 nt (smallest) | 120 nt (5S) to 4700 nt (28S) |
| Stability | Short-lived in eukaryotes | Stable | Very stable |
Structure of DNA
Deoxyribonucleic acid (DNA) is the universal carrier of genetic information. Its double-helix structure was proposed by James Watson and Francis Crick (1953), building on Rosalind Franklin's X-ray diffraction images and Chargaff's rules.
- Two antiparallel polynucleotide strands twisted into a right-handed double helix.
- Sugar-phosphate backbone on the outside; nitrogenous bases face inward.
- Bases pair by hydrogen bonds: A=T (2 H-bonds), G≡C (3 H-bonds).
- 10 base pairs per turn; helix diameter 2 nm; pitch 3.4 nm.
- Sugar = deoxyribose (lacks OH on 2′ carbon).
Chargaff's rules: in any DNA, %A = %T and %G = %C. Total purines (A + G) = total pyrimidines (T + C).
Replication is semi-conservative — each daughter molecule contains one parental and one new strand (Meselson & Stahl, 1958). Nucleotides are linked by phosphodiester bonds between the 3′-OH of one sugar and the 5′-phosphate of the next, giving each strand a 5′→3′ directionality.
A nucleotide is a nitrogenous base + a 5-carbon sugar + one or more phosphates, and nucleotides do far more than build DNA/RNA. ATP (adenine + ribose + 3 phosphates) is the cell's universal energy currency — energy is released when its terminal phosphoanhydride bond is hydrolyzed to ADP + Pi. Related nucleotides include GTP (signaling, translation), cAMP (second messenger), and the electron carriers NAD+, NADP+, and FAD, which are built on adenine nucleotides.
Worked MCQs
Five MCQs that capture the high-yield testing patterns for this chapter.
Q1. At physiological pH (~7.4), which amino acid side chain carries a net positive charge?
Lysine is a basic amino acid; its side-chain amino group is protonated (—NH3+) and positive at pH 7.4. Aspartate and glutamate are acidic (deprotonated, negative), and valine is nonpolar/hydrophobic (uncharged). Knowing the acidic/basic/polar/nonpolar classes is a recurring MCAT skill.
Q2. Cellulose differs from starch primarily in:
Both are polymers of glucose, but cellulose has β-1,4 glycosidic bonds (straight, unbranched fibers) whereas starch has α-1,4 bonds (helical). Humans lack β-1,4 cellulase and cannot digest cellulose.
Q3. The bond that holds two amino acids together in a polypeptide is:
A peptide bond is formed by condensation between the —COOH of one amino acid and the —NH2 of the next, releasing H2O. Glycosidic bonds link sugars, ester bonds link fatty acids to glycerol, and phosphodiester bonds link nucleotides.
Q4. In a DNA molecule, if 30% of the bases are adenine, what is the percentage of cytosine?
By Chargaff's rule, A = T = 30%, so A + T = 60%. Therefore G + C = 40%, and since G = C, each is 20%.
Q5. Which RNA carries the amino acids to the ribosome during translation?
Transfer RNA (tRNA) has a clover-leaf secondary structure with an anticodon at one end and an amino acid attached at the 3′ CCA end; it reads codons on mRNA and delivers the corresponding amino acid.
Quick Recap
- Water: polar, hydrogen-bonded; high specific heat, universal solvent, cohesion-adhesion.
- Carbohydrates: monosaccharides → disaccharides (glycosidic bond) → polysaccharides (starch, glycogen, cellulose, chitin).
- Lipids: triglycerides (glycerol + 3 FA), phospholipids (membranes), steroids (cholesterol, hormones), waxes.
- Proteins: 20 amino acids (nonpolar / polar / acidic / basic R groups), planar peptide bond; primary → secondary → tertiary → quaternary structure; denaturation loses shape, not sequence.
- Enzymes: lower activation energy (not ΔG); active site (induced fit); need cofactors/coenzymes; Michaelis-Menten Km and Vmax.
- ATP = adenine + ribose + 3 phosphates; hydrolysis of the terminal bond powers cellular work.
- DNA: double helix, antiparallel, deoxyribose, A=T, G≡C; phosphodiester backbone; Watson-Crick 1953.
- RNA: single-stranded, ribose, uracil; types — mRNA, tRNA, rRNA.
- Conjugated: glycoproteins, glycolipids, lipoproteins, nucleoproteins.