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Preliminary Examination in Molecular and Cellular Biochemistry

A

  • 1. The subjects of the Preliminary Examination in Molecular and Cellular Biochemistry shall be:

    • (1) Molecular Cell Biology

    • (2) Biological Chemistry

    • (3) Biophysical Chemistry

    • (4) Organic Chemistry

    • (5) Mathematics and Statistics for Biochemists.

  • 2. Candidates shall be deemed to have passed the examination if they satisfy the Moderators in all five subjects.

  • 3. Candidates must offer all five subjects at their first examination attempt.

  • 4. A candidate who fails one or two subjects will be permitted one further attempt at the failed subject/s, at the first available opportunity.

  • 5. A candidate who fails three or more subjects shall be deemed to have failed the examination. He or she will be permitted one further attempt at the whole examination, at the first available opportunity.

  • 6. The Moderators may award a Distinction to candidates of special merit who satisfy them in all five subjects at their first examination attempt.

B

One written paper will be set in each subject. The duration of the written papers will be three hours for subjects 1, 2, and 3, and two and a half hours for subjects 4 and 5. The syllabus for each subject will be that set out in the schedule below.

The Moderators will permit the use of hand-held pocket calculators subject to the conditions set out under the heading ‘Use of Calculators in examinations’ in the Regulations for the Conduct of University Examinations. A list of recommended calculators will be provided by the Chair of the Moderators not later than the Wednesday of the fourth week of the Michaelmas Full Term preceding the examination. The use of calculators may not be permitted in certain papers.

All candidates shall be assessed as to their practical ability in coursework under the following provisions:

  • (a) The Chair of the Teaching Committee, or a deputy, shall make available to the Moderators, at the end of the fifth week of the term in which the examinations are first held, evidence showing the extent to which each candidate has completed the prescribed coursework.

  • (b) The Moderators may request coursework from any candidate. Such candidates will be named in a list posted by the day of the first written paper.

  • (c) Coursework cannot normally be retaken. Failure to complete the coursework to the satisfaction of the Moderators, in the absence of appropriate documentary evidence (e.g. a signed medical certificate), will normally constitute failure of the examination.

Schedule

(1) Molecular Cell Biology

Classification, evolution and structure of bacterial, archeal, and eukaryotic cells; structure of subcellular organelles and the cytoskeleton of eukaryotes. Multicellularity and cell specialization. Differences between plant and animal cells. Nuclear and cell division in plants, animals, and bacteria. Intra- and intercellular signalling.

Chromosomes and genes. Transmission of information between generations. Mitosis and meiosis. Evidence for DNA as the genetic material. The nature of the gene. Organisation and expression of genetic information: mechanism of DNA replication; mechanism and control of transcription; mechanisms and structures involved in protein synthesis; the genetic code; phages, plasmids, and hosts. Gene cloning and mapping techniques.

Major metabolic pathways - chemical and thermodynamic principles. ATP. Oxidation of fuels: glycogen, sugars, amino acids, fats. The TCA cycle. Synthesis of carbohydrates and fats. The glyoxylate cycle. Photosynthesis. Urea cycle.

Structure and properties of biological membranes. Membrane potentials and ion channels. Membrane transport; biological pumps. Bioenergetics; electron transfer, oxidative and photophosphorylation.

(2) Biological Chemistry

Chemical constraints on biology. Energy transformations. Biological polymers. Polysaccharides: amylose and cellulose. Membranes. Lipid and protein components of membranes.

Structure and properties of proteins: amino acids, peptide bonds, conformational preferences, α-helices, β-sheets, stabilisation by non-covalent interactions; protein sequences and amino acid modification; glycoproteins.

Tertiary structure and protein folding. Structural proteins. Myoglobin and haemoglobin.

Principles of enzyme catalysis - acid-base and nucleophilic catalysis. Proteases and other enzymes.

Organic chemistry of enzyme reactions, particularly those in glycolysis.

Biological aspects of sulphur, iron, and phosphorus chemistry.

Organic chemistry of sugars and other heterocyclic compounds.

Structure and properties of nucleic acids; ribose and deoxyribose, keto-enol tautomerism and H-bonding in purines and pyrimidines, phosphate as linking group; nucleotides; polymeric chains of nucleotides; differences in stability between RNA and DNA; the double helix; DNA damage and mutation.

Techniques in molecular biology: purification of DNA and proteins. Electrophoresis. DNA sequencing, cloning, blotting.

(3) Biophysical Chemistry

Principles of Newtonian mechanics and electrostatics. Quantum theory: concepts of quantum mechanics in terms of energy levels. Boltzmann distribution. Atomic and molecular structure, atomic orbitals: crystal field theory; LCAO approach to molecular orbitals.

Electromagnetic radiation and its interaction with matter. Light absorption. Spectroscopy, Beer's Law. Diffraction; Bragg's Law. X-ray diffraction by crystals. Modern optical microscopy. Electron microscopy.

Thermodynamics of solutions: introduction to First and Second Laws. Gibbs function, chemical potential and electrochemical potential. Osmotic equilibria; chemical equilibria; redox equilibria. Buffer solutions and pH. Non-ideal solutions: activity co-efficients. Debye-Huckel theory. Solubility of proteins and other compounds.

Kinetics: order and molecularity; first, second, and pseudo-first order kinetics, steady state. Half lives. Theories of reaction rates; collision theory, transition state theory. Activation energy and the Arrhenius equation. Isotope effects, acid-base catalysis. Radioactive decay as a first order process. Biological effects of radiation. Enzyme kinetics, Michaelis-Menten equation and the steady state derivation. Irreversible and reversible inhibitors of enzymes. Classification of reversible inhibitors. Allostery.

Non-covalent interactions. Electrostatic forces and dipoles. Electronegativity. Lennard-Jones potential and van der Waal's radii. Hydrogen bonding in proteins, DNA and oligosaccharides. The hydrophobic effect; role of entropy. Accessible surface area and solubility. Protein folding—thermodynamic and kinetic aspects. Co-operativity of folding. Protein denaturation and misfolding.

(4) Organic Chemistry

Structure: Elementary atomic and molecular orbital theory. Bonding and molecular geometry. Methods for structure determination (e.g. spectroscopy, mass spectrometry, nmr). Stereochemistry: Absolute configuration. Cis-trans and other isomerisations.

Reactivity: Electronegativity; inductive, mesomeric and stereoelectronic effects. Lowry-Bronsted acidity and basicity of organic compounds. Nucleophilicity and electrophilicity. Simple molecular orbital theory as unifying concept.

Mechanism: Classification of reactions proceeding via intermediates and transition states. Substitution, elimination and addition processes. Rate determining steps; kinetic and thermodynamic control. Carbocation, carbanion, carbene and radical intermediates.

Functional group chemistry: Characteristic chemistry of carbonyl groups. Structure, properties and reactions of carbonyls.

(5) Mathematics and Statistics for Biochemists

An elementary treatment of the following topics will be expected:

Mathematics

Indices, logarithms, and exponential functions. Graphs and graphical representation of simple equations, slopes, inflexion points. Partial fractions. Basic trigonometric functions: sine and cosine functions, representation of waves. Differentiation: maxima and minima; rates of progress, use of Product and Chain rules. Partial differentiation. Integration: of powers of x including x−1; by substitution, by parts and using partial fractions. Introduction to Complex numbers. Simple separable differential equations and their solution. Zeroth, first and second order processes. Permutations and combinations. Factorials and the Binomial Theorem. Binomial and Poisson distributions.

Statistics

Mean, median, and mode—measures of central tendency. Normal, unimodal, and bimodal distributions. Standard deviation, standard error, and coefficient of variance. Confidence limits. Experimental errors and biological variation. Relationships between variables—line fitting. Accuracy and precision. Experimental design. Significance testing; t-tests and non-parametric tests. Conditional probabilities and expectation.