Content Category 5A: Unique nature of water and its solutions

In order to fully understand the complex and dynamic nature of living systems, it is first necessary to understand the unique nature of water and its solutions. The unique properties of water allow it to strongly interact with and mobilize many types of solutes, including ions. Water is also unique in its ability to absorb energy and buffer living systems from the chemical changes necessary to sustain life.

The content in this category covers the nature of solutions, solubility, acids, bases, and buffers.

Topic	Biochemistry	Biochemistry: A Short Course	Biology, 2e	Fundamentals of Biochemistry	Human Physiology	Karp’s Cell and Molecular Biology	Organic Chemistry with a Biological Emphasis, Vol. 1
Acid/Base Equilibria (GC, BC) Bronsted-Lowry definition of acid, base Ionization of water *K_w, its approximate value (K_w* = [H+][OH-] = 10-¹⁴ at 25°C, 1 atm) Definition of pH: pH of pure water Conjugate acids and bases (e.g., NH₄+ and NH3) Strong acids and bases (e.g., nitric, sulfuric) Weak acids and bases (e.g., acetic, benzoic) Dissociation of weak acids and bases with or without added salt Hydrolysis of salts of weak acids or bases Calculation of pH of solutions of salts of weak acids or bases Equilibrium constants K_a and K_b: pK_a, pK_b Buffers Definition and concepts (common buffer systems) Influence on titration curves	Ch. 1 Biochemistry: An Evolving Science, pp. 14-16	Ch. 2 Water, Weak Bonds and the Generation of Order Out of Chaos, pp. 26-31	2.2 Water	Ch. 2 Water: Section 2. Chemical Properties of Water, pp. 31-40	Ch. 20 Fluid, Electrolyte, and Acid-Base Homeostasis, pp. 737-744	Ch. 2 The Chemical Basis of Life, pp. 32-39	Ch. 7.1-7.8, pp. 331-373
Ions in Solutions (GC, BC) Anion, cation: common names, formulas and charges for familiar ions (e.g., NH₄+ ammonium, PO₄^3- phosphate, SO₄^2- sulfate) Hydration, the hydronium ion	NA	Ch. 2 Water, Weak Bonds and the Generation of Order Out of Chaos, pp. 18-23	NA	Ch. 2 Water: Section 2. Chemical Properties of Water, pp. 31-40	Ch. 2 Chemical Composition of the Body, pp. 25-29	Ch. 2 The Chemical Basis of Life, pp. 32-39	NA

nibrown@aamc.org Thu, 07/13/2023 - 16:53

Content Category 5B: Nature of molecules and intermolecular interactions

Covalent bonding involves the sharing of electrons between atoms. If the result of such interactions is not a network solid, then the covalently bonded substance will be discrete and molecular.

The shape of molecules can be predicted based on electrostatic principles and quantum mechanics since only two electrons can occupy the same orbital. Bond polarity (both direction and magnitude) can be predicted based on knowledge of the valence electron structure of the constituent atoms. The strength of intermolecular interactions depends on molecular shape and the polarity of the covalent bonds present. The solubility and other physical properties of molecular substances depend on the strength of intermolecular interactions.

The content in this category covers the nature of molecules and includes covalent bonding, molecular structure, nomenclature, and intermolecular interactions.

Topic	Organic Chemistry with a Biological Emphasis, Vol. 1
Covalent Bond (GC) Lewis Electron Dot formulas Resonance structures Formal charge Lewis acids and bases Partial ionic character Role of electronegativity in determining charge distribution Dipole Moment σ and π bonds Hybrid orbitals: sp³, sp², sp and respective geometries Valence shell electron pair repulsion and the prediction of shapes of molecules (e.g., NH3, H2O, CO2) Structural formulas for molecules involving H, C, N, O, F, S, P, Si, Cl Delocalized electrons and resonance in ions and molecules Multiple bonding Effect on bond length and bond energies Rigidity in molecular structure Stereochemistry of covalently bonded molecules (OC) Isomers Structural isomers Stereoisomers (e.g., diastereomers, enantiomers, cis/trans isomers) Conformational isomers Polarization of light, specific rotation Absolute and relative configuration Conventions for writing R and S forms Conventions for writing E and Z forms	Ch. 1.1-3.9, pp. 5-173
Liquid Phase - Intermolecular Forces (GC) Hydrogen bonding Dipole Interactions Van der Waals’ Forces (London dispersion forces)	Ch. 1.4B-D

Topic

Organic Chemistry with a Biological Emphasis, Vol. 1

Covalent Bond (GC)

Lewis Electron Dot formulas
- Resonance structures
- Formal charge
- Lewis acids and bases
Partial ionic character
- Role of electronegativity in determining charge distribution
- Dipole Moment
σ and π bonds
- Hybrid orbitals: sp³, sp², sp and respective geometries
- Valence shell electron pair repulsion and the prediction of shapes of molecules (e.g., NH3, H2O, CO2)
- Structural formulas for molecules involving H, C, N, O, F, S, P, Si, Cl
- Delocalized electrons and resonance in ions and molecules
Multiple bonding
- Effect on bond length and bond energies
- Rigidity in molecular structure
Stereochemistry of covalently bonded molecules (OC)
- Isomers
  - Structural isomers
  - Stereoisomers (e.g., diastereomers, enantiomers, cis/trans isomers)
  - Conformational isomers
- Polarization of light, specific rotation
- Absolute and relative configuration
  - Conventions for writing R and S forms
  - Conventions for writing E and Z forms

Ch. 1.1-3.9, pp. 5-173

Liquid Phase - Intermolecular Forces (GC)

Hydrogen bonding
Dipole Interactions
Van der Waals’ Forces (London dispersion forces)

Ch. 1.4B-D

nibrown@aamc.org Thu, 07/13/2023 - 17:01

Content Category 5C: Separation and purification methods

Analysis of complex mixtures of substances ― especially biologically relevant materials ― typically requires separation of the components. Many methods have been developed to accomplish this task, and the method used is dependent on the types of substances which comprise the mixture. All these methods rely on the magnification of potential differences in the strength of intermolecular interactions.

The content in this category covers separation and purification methods including extraction, liquid and gas chromatography, and electrophoresis.

Topic	Biochemistry	Biochemistry: A Short Course	Fundamentals of Biochemistry	Karp’s Cell and Molecular Biology
Separations and Purifications (OC, BC)* Extraction: distribution of solute between two immiscible solvents Distillation Chromatography Basic principles involved in separation process Column chromatography, gas-liquid chromatography High pressure liquid chromatography Paper chromatography Thin-layer chromatography Separation and purification of peptides and proteins (BC) Electrophoresis Quantitative analysis Chromatography Size-exclusion Ion-exchange Affinity Racemic mixtures, separation of enantiomers (OC)	Ch. 3 Exploring Proteins and Proteomes, pp. 69-105	Ch. 5 Techniques in Protein Biochemistry, pp. 75-98	Ch. 5 Proteins: Primary Structure: Section 2. Protein Purification and Analysis, p. 99-108	Ch. 18 Techniques in Cell and Molecular Biology, pp. 692-716

nibrown@aamc.org Thu, 07/13/2023 - 19:45

Content Category 5D: Structure, function, and reactivity of biologically-relevant molecules

The structure of biological molecules forms the basis of their chemical reactions including oligomerization and polymerization. Unique aspects of each type of biological molecule dictate their role in living systems, whether providing structure or information storage, or serving as fuel and catalysts.

The content in this category covers the structure, function, and reactivity of biologically-relevant molecules including the mechanistic considerations that dictate their modes of reactivity.

Topic	Biochemistry	Biochemistry: A Short Course	Biology, 2e	Fundamentals of Biochemistry	Human Physiology	Karp’s Cell and Molecular Biology	Organic Chemistry with a Biological Emphasis, Vol. 1	Organic Chemistry with a Biological Emphasis, Vol. 2
Nucleotides and Nucleic Acids (OC, BC, BIO)* Nucleotides and nucleosides: composition Sugar phosphate backbone Pyrimidine, purine residues Deoxyribonucleic acid: DNA; double helix Chemistry (OC, BC) Other functions (OC, BC)	Ch. 4 DNA, RNA and the Flow of Genetic Information, pp. 114-124	Ch. 33 The Structure of Informational Macromolecule: DNA and RNA, pp. 673-690	3.5 Nucleic Acids	Ch. 3 Nucleotides, Nucleic Acids, and Genetic Information, pp. 42-79	Ch. 2 Chemical Composition of the Body, pp. 52-54	Ch. 2 The Chemical Basis of Life, pp. 77-79 Ch. 10 The Nature of the Gene and the Genome, pp. 373-377, 382-387 Ch. 18 Techniques in Cell and Molecular Biology, pp. 721-722	Ch. 1.3E, pp. 43-45	Ch. 9.1-9.8, pp. 1-38
Amino Acids, Peptides, Proteins (OC, BC)* Amino acids: description Absolute configuration at the α position Dipolar ions Classification Acidic or basic Hydrophilic or hydrophobic Synthesis of α-amino acids (OC) Strecker Synthesis Gabriel Synthesis Peptides and proteins: reactions Sulfur linkage for cysteine and cystine Peptide linkage: polypeptides and proteins Hydrolysis General Principles 1° structure of proteins 2° structure of proteins 3° structure of proteins Isoelectric point	Ch. 2 Protein Composition and Structure, pp. 29-64	Ch. 3 Amino Acids, pp. 37-45 Ch. 4 Protein Three-Dimensional Structure, pp. 49-68	3.4 Proteins	Ch. 4 Amino Acids, pp. 80-96	Ch. 2 Chemical Composition of the Body, pp. 45-52	Ch. 2 The Chemical Basis of Life, pp. 58-70	Ch. 1.3D, pp. 41-43	Ch. 11.1-11.7, pp. 95-124 Ch. 15.6, pp 309-316
The Three-Dimensional Protein Structure (BC) Conformational stability Hydrophobic interactions Solvation layer (entropy) 4° structure Denaturing and folding	Ch. 2 Protein Composition and Structure, pp. 52-62	Ch. 4 Protein Three-Dimensional Structure, pp. 62-67	3.4 Proteins	Ch. 6 Proteins: Three-Dimensional Structure, pp. 131-179	Ch. 2 Chemical Composition of the Body, pp. 45-52	Ch. 2 The Chemical Basis of Life, pp. 48-70	NA	NA
Nonenzymatic Protein Function (BC) Binding Immune system Motor	Ch. 7 Hemoglobin, pp. 207-227 Ch. 35 Immune System, pp. 1119-1145 Ch. 36 Molecular Motors, pp. 1151-1168	Ch. 9 Hemoglobin, an Allosteric Protein, pp. 161-173	NA	Ch. 7 Protein Function: Myoglobin and Hemoglobin, Muscle Contraction and Antibodies, pp. 180-220	Ch. 2 Chemical Composition of the Body, pp. 45-52	Ch. 2 The Chemical Basis of Life, pp. 73-76 Ch. 7 Interactions Between Cells and Their Environment, pp. 238-241 Ch. 9 The Cytoskeleton and Cell Motility, pp. 315-320	NA	NA
Lipids (BC, OC)* Types Storage Triacyl glycerols Free fatty acids: saponification Structural Phospholipids and phosphatids Sphingolipids Waxes Signals/cofactors Fat-soluble vitamins Steroids Prostaglandins	Ch. 12 Lipids and Cell Membranes, pp. 373-380 Ch. 26 The Biosynthesis of Membrane Lipids and Steroids, pp. 849-883	Ch. 29 Lipid Synthesis: Storage Lipids, Phospholipids and Cholesterol, pp. 577-601	3.3 Lipids	Ch. 9 Lipids and Biological Membranes, pp. 245-292	Ch. 2 Chemical Composition of the Body, pp. 40-45 Ch. 4 Metabolism, pp. 126-127	Ch. 2 The Chemical Basis of Life, pp. 46-49 Ch. 4 The Structure and Function of the Plasma Membrane, pp. 118-122	Ch. 1.3A, pp. 35-39	Ch. 11.6, pp. 116-121
Carbohydrates (OC)* Description Nomenclature and classification, common names Absolute configuration Cyclic structure and conformations of hexoses Epimers and anomers Hydrolysis of the glycoside linkage Keto-enol tautomerism of monosaccharides Disaccharides (BC) Polysaccharides (BC)	Ch. 11 Carbohydrates, pp. 341-365	Ch. 10 Carbohydrates, pp. 181-201	3.2 Carbohydrates	Ch. 8 Carbohydrates, pp. 221-245	Ch. 2 Chemical Composition of the Body, pp. 36-40	Ch. 2 The Chemical Basis of Life, pp. 41-46	Ch. 1.3C, pp. 39-43 Ch. 3.2 pp. 137-146 Ch. 3.6, pp. 161-168 Ch. 3.8, pp. 171-173	Ch. 10.1-10.3, pp. 53-71 Ch. 12.2 A-B, pp. 153-157
Phenols (OC, BC) Oxidation and reduction (e.g., hydroquinones, ubiquinones: biological 2e- redox centers)	NA	NA	NA	Ch.14 Introduction to Metabolism: Section 3. Oxidation-Reduction Reactions, pp. 461-466	NA	NA	NA	Ch. 15.1-15.4, pp. 278-307
Polycyclic and Heterocyclic Aromatic Compounds (OC, BC) Biological aromatic heterocycles	NA	NA	NA	Ch. 3 Nucleotides, Nucleic Acids and Genetic Information: Section 1. Nucleotides, pp. 43	NA	NA	NA	NA

nibrown@aamc.org Thu, 07/13/2023 - 21:25

Content Category 5E: Principles of chemical thermodynamics and kinetics

The processes that occur in living systems are dynamic, and they follow the principles of chemical thermo-dynamics and kinetics. The position of chemical equilibrium is dictated by the relative energies of products and reactants. The rate at which chemical equilibrium is attained is dictated by a variety of factors: concentration of reactants, temperature, and the amount of catalyst (if any).

Biological systems have evolved to harness energy and utilize it in very efficient ways to support all processes of life, including homeostasis and anabolism. Biological catalysts, known as enzymes, have evolved to allow all the relevant chemical reactions required to sustain life to occur both rapidly and efficiently, and under the narrow set of conditions required.

The content in this category covers all principles of chemical thermodynamics and kinetics including enzymatic catalysis.

Topic	Biochemistry	Biochemistry: A Short Course	Biology, 2e	Fundamentals of Biochemistry	Human Physiology	Karp’s Cell and Molecular Biology	Organic Chemistry with a Biological Emphasis, Vol. 1	Organic Chemistry with a Biological Emphasis, Vol. 2
Enzymes (BC, BIO) Classification by reaction type Mechanism Substrates and enzyme specificity Active site model Induced-fit model Cofactors, coenzymes and vitamins Kinetics General (catalysis) Michaelis-Menten Cooperativity Effects of local conditions on enzyme activity Inhibition Regulatory enzymes Allosteric Covalently modified	Ch. 8 Enzymes: Basic Concepts and Kinetics, pp. 223-264 Ch. 9 Catalytic Strategies, pp. 273-306 Ch. 10 Regulatory Strategies, pp. 303-335	Ch. 6 Basic Concepts of Enzyme Action, pp. 105-115 Ch. 7 Kinetics and Regulation, pp. 119-134 Ch. 8 Mechanisms and Inhibitors, pp. 143-156	6.5 Enzymes	Ch. 17 Enzyme Kinetics, Inhibition, and Control, pp. 346-401	Ch. 2 Chemical Composition of the Body, pp. 51-52 Ch. 4 Energy and Metabolism, pp. 102-106 Ch. 21 The Digestive System, pp. 762-763	Ch. 3 Bioenergetics, Enzymes, and Metabolism, pp. 89-100, 106, 109-110	Ch. 6.3-6.4, pp. 320-324	Ch. 16.5, pp. 355-360 Ch. 17.7-17.4, pp. 369-412
Principles of Bioenergetics (BC) Bioenergetics/thermodynamics Free energy/K^eq Concentration Phosphorylation/ATP ATP hydrolysis ΔG << 0 ATP group transfers Biological oxidation-reduction Half-reactions Soluble electron carriers Flavoproteins	Ch. 8 Enzymes: Basic Concepts and Kinetics, pp. 236-239 Ch. 15 Metabolism: Basic Concepts and Design, pp. 463-475 Ch. 18 Oxidative Phosphorylation, pp. 576-582	Ch. 6 Basic Concepts of Enzyme Action, pp. 108-114 Ch. 15 Metabolism: Basic Concepts, pp. 286-292 Ch. 20 The Electron-Transport Chain, pp. 402-413	6.1 Energy and Metabolism 6.2 Potential, Kinetic, Free, and Activation Energy 6.3 The Laws of Thermodynamics	Ch. 18 Electron Transport and Oxidative Phosphorylation, pp. 588-629	Ch. 4 Metabolism, pp. 100-113	Ch. 3 Bioenergetics, Enzymes, and Metabolism	Ch. 6.2-6.4, pp. 312-324	Ch. 9.1-9.6, pp. 4-32 Ch. 15.1-15.2, pp. 278-287 Ch. 15.4B, pp. 303-307

nibrown@aamc.org Thu, 07/13/2023 - 21:51

Foundational Concept 5

Content Categories:

Content Category 5A: Unique nature of water and its solutions

Content Category 5B: Nature of molecules and intermolecular interactions

Content Category 5C: Separation and purification methods

Content Category 5D: Structure, function, and reactivity of biologically-relevant molecules

Content Category 5E: Principles of chemical thermodynamics and kinetics