Transcript Crash Course in Biochemistry

Crash Course in Biochemistry
…4 years in 40 min!
Nick Lyle
Proteins – What are they?
• Not just a dietary concern !
• Numerous activities in all organisms:
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Structural & Transport
Enzymatic (Like Machines -> real nano-tech)
Signaling & Regulatory
Generalization: Responsible for all rXns. in
your body (ask aud. examples)
Structural Examples
• Keratin
– Makes up hair and nails
– Disulfide bond hold coilcoil together
– Perm: Break disulfides and
reform them
Structural Examples
• Cell Adhesion:
– Helps cells stick
to other cells.
Immunological cells
find their target
• Cytoskeleton:
– Protein scaffold to which cellular
components hitch a ride on
Enzymatic Examples
• Enzymes run chemical reactions
• Substrate  Product
• Usually 1 unique protein for EVERY
unique reaction
Enzymatic Examples
• Glycolysis:
– Get energy from
breaking down
sugar
– Universal
• The Process:
–
See: http://www.rcsb.org/pdb/molecules/pdb50_1.html
So Many Reactions!
Enzymatic Examples
• Notice: Specific protein at every step
• This just a tiny fraction of what we
know
• Like a circuit: Where our knowledge
of CS is useful
• Drugs: are ways to ‘hack’ the circuit
by changing protein behavior
– Caffeine
– Statins and Cholesterol
Caffeine Example
• Epinepherine stimulates production
of cAMP
• cAMP increases rate of many rXn’s,
including glycolysis (PFK)
• Phosphodiesterase eliminates cAMP
• Caffeine is a phosphodiesterase
Inhibitor
Enzymatic + structural example
• Muscles: Use ATP to move
Carrier Example
• Hemoglobin: Carries Oxygen
Transport Example
• Sodium-potassium pump
– Net Effect: push positive charge outside
– Electrical field made used for nerve
conduction
What are proteins?
• Like magnetic beads on a string
• 20 different beads possible (amino
acids)
- The sidechain (R-group) is the
difference between the 20 AA’s.
- Hook together like Legos, 1 way to
connect
- Backbone repeats
20 Possible Amino Acids
• Common to all life
What are proteins?
• Regular protein 100-400 AA’s
Protein Folding:
Sidechains attract and repel each other, surround water pushes
and pulls (hydrophobic, hydrophilic). This force mashes the protein
into a particular shape.
Simulated folding animation:
http://intro.bio.umb.edu/111-112/111F98Lect/folding.html
Protein Structure
• Folding results in only 1
conformation (structure or fold)
• Sequence determines structure
• Structure determines function
• Structure VERY important
– Gives insights to how protein works
– Cant drive with square wheels
– Heat denatures proteins
– Digestive Zymogens
• Sequence  structure
computationally impossible
Structure and Active site
• Part of protein where reaction occurs
What if shape different? RuBP won’t bind, No reaction.
Some mutations change critical active site residues.
Genetic Mutations and Disease: sickle cell, PKU
Protein-Protein Docking
• Some proteins bind (stick) to each
other in a highly specific way
– See hemoglobin
• The final complex is functional
• Individual pieces
are not
– Toxic truncated
peptides
• RNA polymerase
How are Proteins Made?
• DNA is set of instructions (Opcode)
– Bases like
sidechains
– A-T G-C
– Like many
programs
concatenated
together
Genes…
• 1 gene makes 1
protein
• Genes separated
by control regions
• Tells where genes
start and stop
• This still not well
understood
Genes read by RNA polymerase
• Regulatory regions attract TF’s,
which attracts RNA poly.
• RNA (single strand) is a
copy of a gene
Ribosome: RNA Protein