Transcript Biochemistry for Bioinformaticians

Better Living Through
Biochemistry
figuring it all out from the bottom up
Finding a Date in Paris
• First must deal with language barrier!
• Review hospital records, decide brain
necessary for language.
• Dissect brain, note it has many neurons.
• Neurons conduct electricity? What the @#$*?!!
• Possibly result of weird ‘channeling’ molecules in
membranes.
• Molecules are made of atoms sharing electrons.
• Electrons move according to Schrodinger’s
equation!
To get a date in Paris just need
to solve Schrodinger’s Equations!!!
3 Years and 3,000,000 CPU
Hours Later…
• Realize Schrodinger’s equation is hard to
solve past the hydrogen atom.
• It’s not an entire waste though, simple
Schrodinger solutions help explain
tetrahedral arrangement of covalent bonds
around a carbon atom.
• Hmm, perhaps *chemistry*, not physics is
the key to finding a date in Paris!
Schrodinger’s Tetrahedrons
Basic Chemistry
• For cool quantum reasons, atoms like having 8
electrons in their ‘valence’ shells.
• Elements in columns of the periodic table have the
same # of valence electrons.
• Elements with 5 or more valance electrons will
tend to grab electrons from elements with 3 or
less. (Having 0 electrons in outer shell is also
quantumly stable.)
• Carbon has 4 valance electrons, can go either way.
Chemical Bonds
• Electrons can transferred completely from
one atom to another. This creates a pair of
ions – one negatively and one positively
charged. Opposite charges attract leading
to an ‘ionic’ bond.
• Electrons can also be shared by both atoms,
leading to a ‘covalent’ bond. Covalent
bonds can involve 1, 2, or 3 electrons.
Electronegativity & Covalent
Bonds
• Electrons are shared in a covalent bond, but not
necessarily shared equally.
• Water is made up of oxygen bonded covalently to
two hydrogens.
• Oxygen (6 valance electrons wanting 8) tends to
get most of electrons rather than hydrogen (1
valance electron wanting 0)
• The H-O bond is ‘polar.’ There is a fractional
negative charge on the oxygen, a fractional
positive charge on the hydrogen.
Polarity of Common Bonds
• H-O is the most polar bond that is common in
biology.
• H-N bond is also quite polar.
• C=O bond is fairly polar.
• H-S bond is somewhat polar.
• S-C bond not very polar
• C-H bond is almost entirely non-polar.
• C-C bond is entirely non-polar.
Weak Interactions: Polar Bonds
• Polar Bond/Ion attraction. Based on charge. Leads
to salt dissolving readily in water.
H+-O- … Na+
• Polar Bond/Polar Bond – also charge based
C+= O- … C+= O• Hydrogen Bonds – polar bond/polar bond where
hydrogen is practically shared. Has a semicovalent aspect. Like covalent bonds has
geometrical constraints
H+ - O-…H+-O~ 5% the strength of a covalent bond.
A Very Important Set of Hydrogen Bonds
The Secret of Salad Dressing
• Water with H-O-H mixes well with itself,
lots of opportunity for hydrogen bonding.
• Water will prefer sticking to itself to mixing
with C-H (hydrocarbon) materials leading
to so called ‘hydrophobic forces’ that
separate oils and waters.
• Hydrophobic forces involve entropy as well
as energy.
Weak Interactions:
Van Der Waals Forces
Orbits of electrons synchronize so that
electrons in neighboring molecules stay as
far away from each other as possible:
+
-
+
-
This leads to a very weak very short range
attraction perhaps 1% as strong as a
covalent bond.
Velcro Chemistry
• Large molecules shaped to fit well against
each other can stick quite tightly from large
numbers of weak interactions. This can
even help catalyze reactions.
Basic Classes of Biochemicals
• Lipids: mostly hydrocarbons. Form cell
membranes and used for energy storage.
• Carbohydrates: sugar monomers can be joined to
form starch and cellulose.
• Nucleic acids: formed from nucleotide monomers.
DNA & RNA store and circulate information
primarily.
• Proteins: formed from amino acid monomers.
Diverse in shape and function. Basis of most
enzymes.
Lipids
• Triacylglycerides: used for energy storage.
The $100.00 bills of the cell. Three long
hydrocarbon chains joined to glycerol.
• Phospholipids: Two long hydrocarbon
chains joined to a phosphate (charged) head
group. The main component of membranes.
• Sterols: Many-ringed non-polar structures.
Cholesterol strengthens cell membranes.
Testosterone & estrogen are also sterols.
Carbohydrates
• Most composed of 6-carbon sugars, which are
produced during photosynthesis. Glucose is the
$20 bill of the cell. Mostly is a semi-rigid ring.
• Table sugar is glucose and fructose joined.
(Fructose converts to glucose easily.)
• Starch is glucose joined together in a branched
form that is easily converted back to glucose.
• Cellulose is glucose joined together in a straight
form that is relatively hard to convert back to
glucose.
• Fancy sugars decorate outside of animal cells.
Nucleic Acids
• Nucleic acids are synthesized from
nucleotide-tri-phosphates (NTPs).
• ATP is an aromatic base (A) linked to a five
carbon sugar (ribose) and three phosphates (PO4-)
• ATP is the dollar bill of the cell. The reaction ATP
-> ADP directly powers most of cell.
• dATP is like ATP but with one oxygen removed
from the ribose, which makes it more stable.
• RNA is made from NTPs, DNA from dNTPs
Proteins
• Proteins are made up of 20
different amino acids.
• All amino acids share common
central structure which forms
backbone of proteins.
• Side chains of amino acids can be non-polar,
polar, charged, and aromatic.
• Proteins may fold into a specific shape or remain
fairly wiggly.
• Cell often adds phosphates to OH groups on side
chains to modulate shape and activity
The Cell Membrane
How A Nerve Cell Fires
• Nerve cell memberne is a lipid bilayer with
embedded proteins.
• ATP-powered ion pumps keep outside of
membrane + charged, inside – charged.
• Channels in membrane can let + ions pass
through. Channels normally closed.
• Neurotransmitter gated channels collapse
(‘depolarize’) voltage gradient.
• Voltage gated channels propagate depolarization in
a wave down axon.
Conclusion
• Careful study of biochemistry and
macromolecules enables bottom up
understanding of how a nerve works.
• Bottom up understanding of how French
works should not be much harder.
• It’s very likely the astute biochemist will get
laid *next* time they go to Paris.