Jeffjar’s Notes on Biochemistry

How do cells work? How does life-like behavior emerge out of the wigglings and jigglings of floppy molecules? Biochemistry tells the remarkable story of how life is created out of the hard laws of physics – often in crafty, surprising, and beautiful ways.

I’m writing up a few notes on biochemistry for a number of reasons:

• to share my fascination of Nature’s inner workings.
• to practice clear scientific writing.
• to refresh and solidify my own understanding of biochemistry.
• to put out my own physicsy viewpoint of biochem.

My traget audience will be a younger version of myself who’s just at the brink of learning biochemistry. (Writing for a mini-jeffjar will also let my own scientific voice shine through!) Back then, I had a cursory knowledge of statistical mechanics, and I could recognize basic organic molecules, but not much more. So in these notes, I’ll include any relevant background beyond introductory physics and organic chemistry.

I hope you enjoy these notes!

Outline

• Statistical Mechanics governs what life can do and cannot do.
  • Fundamental assumptions about equilibrium and entropy
  • Describing subsystems using the Boltzmann factor and free energy
  • The equipartition theorem explains temperature
  • Chemical potential
  • Diffusion and fluctuations
• Proteins are the building blocks of cellular machines.
  • Amino acid chemistry
  • 1,2,3,4 structure and “the folding question”
  • Lengthscales and timescales. Dynamics, energetics, etc.
  • Experimental techniques. X-ray crystallography
• Cellular structure
  • Motivation: What are the parts of the puzzle?
  • Central dogma, cellular components. Basic lengthscales/timescales.
  • DNA/RNA structure and function. Physical properties, free energy challenges.
  • Lipid physical chemistry.
  • “Macromolecular crowding” and the cellular interior.
• Enzymology
  • Motivation: How does biology do chemistry?
  • Michaelis-Menten kinetics (phenomenology).
  • Bells’n’whistles: inhibition, multi-step, multi-substrate, cooperativity, etc.
  • P.chem theories of catalysis.
  • Philosophy of “switching ensembles” and the 2nd law?
  • Examples of types of possible reactions. Co-factors.
• Metabolism
  • Motivation: What exact chemistry underlies bioenergetics?
  • Macro-scale catabolism/anabolism, extracting free energy from food.
  • Themes of small chemical steps, specificity, regulation, localization, Delta-G coupling
  • The canonical pathway: glycolysis/citric acid cycle/respiration. Redox chem, #’s.
  • Glycolysis. G6P to keep inside cell. Regulation.
  • Citric Acid Cycle. PDH as “quinary structure”. Ridiculous interior of mitochondria.
  • Respiration. ATP synthase as a free-energy-couple.
• More Metabolism
  • Motivation: Get a better sense of how Nature makes other things.
  • Nucleobase biosynthesis
  • Amino acid metabolism, the “ammonia problem”.
  • Beta-oxidation, impossible chemistry.
  • Gluconeogenesis and glycogen.
• Signalling
  • GPCRs, cascades, amplification, cross-talk, timescales, logic, etc...
• Transcription and Translation
  • What happens inside DNA polymerases and ribosomes
  • Kinetic proofreading; bounds on accuracy, speed, energy usage.