reviewing the basics what is life/biochemistry? –“complex and organized” –self-replicating...
TRANSCRIPT
Reviewing the Basics
• What is life/biochemistry?
– “Complex and organized”– Self-replicating (cellular molecules)– Dynamic steady state– Energy transduction
Important biological macromolecules
are polymers
DNA, RNA are made from nucleotides
– which themselves are comprised of bases, carbohydrates, and phosphate
Proteins are polypeptides
NH3+-C-COO-
R
H
Amino acids provide a great example of biological
stereoisomers• Proteins are composed nearly exclusively of L-
amino acids• However, D-amino acids can serve a physiological
role also.– D-Serine has a potential role as a human
neurotransmitter, and D-alanine has a defined role in microbial cell wall biosynthesis
– Cells synthesize proteins (enzymes) called isomerases, epimerases, or racemases that specifically to interconvert biological stereoisomers
Conformation vs. Configuration
• Configuration refers to spatial arrangement of atoms (fig. 1-18)
• Conformation refers to rotation about single bonds (fig. 1-21)
• Biomolecules are synthesized and modified to adopt stereospecific structures that allow for specific interactions and reactions
Lipids are often underrated carbon polymers
Cell and organelle membranes (define self; key for biological energy generation)
Protein modifications
Energy Storage
Hormones
Etc.
Glycobiology is huge
• Carbohydrates are multi-functional molecules and often form polymers in these functions such as energy storage
• Determining patterns and effects of protein glycosylation in eukaryotes is a top priority in many proteomic initiatives
• Glycolysis and carbohydrate metabolism is often used as a “common” model for energy transduction among organisms in biochemistry courses
Biology is primarily an aqueous system
• Most organisms are made of ~70% H2O• If you dried down a cell this is what you’d see:
Macromolecular composition of E. coli strain B/r grown under a standard culture condition (i.e., balanced growth, glucose minimal medium, 37°C, mass doubling time of 40 min.):
Macromolecules:
Protein 55% (of total dry weight)
RNA 20.5%
DNA 3.1%
Lipid 9.1%
Lipopolysaccharide 3.4%
Murein 2.5%
Glycogen 2.5%
Soluble pool
(amino acids,
vitamins, etc.) 2.9%
Inorganic ions 1.0%
Interactions between macromolecules must “deal” with water
This aqueous environment has interesting chemical properties
bond length of 1.8 Angstroms
Angstrom = 10-10 m
Hydrogen bonds are pervasive in biology
• Between water and biomolecules• Between nucleotides (DNA)• Between amino acids (proteins)
• The directionality of H-bonds confers precise 3-D structures
Directionality also affects strength
Polarity intrinsic to many molecules
Water affects electrostatics
• Hydrophilic (polar, charged molecules; salt) vs. Hydrophobic (non-polar; lipids)
• Water screens electrostatic charges (high dielectric constant)
F = Q1Q2/r2
Ionization has a profound effect on many of these interactions
• The charge on many biomolecules is pH dependent
• pH = -log[H+]
• pKa = -log Ka– The stronger the tendency to dissociate a
protein, the stronger the acid, the lower the Ka
Ka = [H+] [A-]/[HA]
Titration curves reveal pKa’s
Henderson-Hasselbach equation
pH = pKa + log [unprotonated/protonated]
HA H+ + A-
Ka = [H+] [A-] [HA]
[H+] = Ka[HA] [A-]
-log[H+] = -log Ka - log [HA]/[A-]
Biological reactions are tuned to specific pH’s
Buffers maintain pH
pH is stabilized around the pKa of a buffer as observed in titration curves and Henderson-Hasselbachequation
Hydrophobic interactions are a driving force in biology
• Key for membranes and proteins
• Hydrophobic molecules interact with one another breaking H-bonding patterns in water
• Many biomolecules are amphipathic with regions of both hydrophobic and hydrophilic character
Van der Waal interactions are caused by instantaneous dipoles
• At less than 1 kcal/mole these interactions have considerably less energy than:– H-bonds ~3-5 kcal/mole or 20 kJ/mol– Electrostatic interactions ~4-7 kcal/mole– Hydrophobic interactions- can vary, most data
from simulations ~1.5 kcal/mole CH4 in water, ~5 kcal/mole amino acid in a protein
Biochemistry from a cellular view is all about
energy transduction
Biomolecules are in a constant dynamic steady state
Cells convert environmental nutrients into energy to be used
for work– Synthesis– Mechanical– Osmotic and electrical gradients– Light production– Information storage
Enzymes catalyze biological reactions
ATP is central to cellular energy
…and cellular ATP generation is all about movement of protons
and electrons• Although the sun is the primary energy
producer, oxidation-reduction reactions drive energy production
• This energy production is generated via catabolic processes (exergonic) and used in anabolic processes (endergonic) for work
Redox reactions involve electron transfer
For instance, Formate dehydrogenase (ineffectiveness of this enzyme leads to liver damage from methanol ingestion)
HCOOH CO2
2 H+ + 2 e-
2 H+ + 2 e-
Flow of electrons can do biological work
• Movement of electrons through a electron transport chain generates a protonmotive force which leads to ATP synthesis, but before covering the Mitchell hypothesis –
• What is meant by biological work?