Download BIOMG 3310: Principles of Biochemistry

BIOMG 3310
Professor Feigenson
Fall 2016
Week 2: Lecture 1 of 3
Monday, August 29th
Lecture Keywords: aliphatic hydroxyl amino acids, acidic amino acids, amide amino acids, basic
amino acids, ubiquitin, proline, hydrophobic interaction, protein modification
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The Henderson-Hasselbalch equation indicates several things.
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Molecules with higher pKas have greater affinities for H+.
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If the pH is significantly greater than the pKa, the H+ is predominantly off.
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If the pH is significantly lower than the pKa, the H+ is predominantly on.
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If the pH is equal to the pKa, the [unprotonated][protonated]=1.
The pKa is affected by the molecule’s ionization behavior.
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The pKa changes depending on the local environment of the group.
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If the negatively charged ion is near a positively charged ion, the pKa will decrease
because the unprotonated form is favored due to the increased stability.
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If the negatively charged ion is near another negatively charged ion, the pKa will
increase because the protonated form is favored due to decreased stability of the
anion.
The concentration of H+ can be a signal in biochemistry.
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For example, when a hemoglobin protein molecule encounters a low pH, it drops off
the oxygen.
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This causes the concentration of H+ to increase, resulting in the formation of
more ion pairs, thereby changing the structure of hemoglobin.
There are two aliphatic hydroxyl amino acids, serine and threonine.
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The hydroxyl group is often involved in chemical modification.
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For example, the OH group in Ser can be replaced by a phosphate group.
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Phosphorylation is the most common type of chemical modification.
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There are two acidic amino acids, aspartate (i.e. aspartic acid) and glutamate (i.e. glutamic
acid).
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They both are usually negatively charged at physiological pH (i.e. pH = 7) because their
side chain pKas range from 3 to 5.
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This allows them to interact well with water.
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They can act by catalysis by donating or accepting H+.
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Chemical modification typically happens after folding.
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Aspartate is connected to nucleotides.
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This means that two types of metabolism (amino acid metabolism and RNA/DNA
metabolism) are also connected.
There are two amide amino acids, asparagine and glutamine.
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They never accept or donate H+ even though they’re good H-bond donors and acceptors.
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When they bind to sugar, the sugar molecule bonds to the N, which is the site of chemical modification.
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These amino acids are never charged.
There are three basic amino acids, lysine, arginine, and histidine.
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Lysine has a pKa of 10 (and is therefore usually positive charged at physiological pH)
and is involved in two major roles.
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It is involved with histones, the proteins that bind to DNA to control DNA activity.
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Ubiquitin is found in every cell and marks other proteins to be broken down by
proteases.
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Arginine has a pKa of 12, which is the highest of all side chains; because it has such a
high pKa, it’s essentially always positively charged and has a proton attached.
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Histidine has a pKa of 7, so it’s very easy to add and remove a proton at physiological
pH.
Proline is the amino acid that is categorized by itself.
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Its side chain forms a ring with the alpha carbon, which affects how it behaves in proteins.
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Adding groups via chemical modification changes the way the histones affect the
DNA.
It can also add a protein called ubiquitin.
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When Ser is part of an enzyme, this modification changes the enzyme.
The side chain motion is restricted due to the presence of the ring.
It loses a H from the N, so it cannot be an H-bond donor when it’s in proteins.
Amino acids are, in general, soluble in water.
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Peptide bond formation results in dehydration (i.e. the loss of one molecule per peptide bond
formed).
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This also causes the loss of one positive and one negative charge, which changes the
amino acid behavior because the behavior of the free amino acid is dependent upon the
amino acid having two charges.
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Polypeptides are much less soluble in water than individual amino acids are.
The hydrophobic interaction is very important to biochemistry.
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Each water molecule can form 3-4 H-bonds and has about 10 neighboring molecules.
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Hydrophobic molecules do not form H-bonds, and when they are in water, they restrict
water’s ability to form H-bonds.
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However, tyrosine is not soluble in water because it forms very stable crystals.
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Therefore, the molecules fold to minimize contact with water, thereby allowing water to have more opportunities to H-bond with its neighbors.
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The hydrocarbon side chains are driven out of contact with the water, forming a
“core”.
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The polar region of the protein remains on the outside, touching the water.
The hydrophobic interaction impacts the ΔS component of the free energy function.
Sidechain polarity affects which parts of proteins are internal.
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The detailed ordering of side chains according to polarity depends on the structure.
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The order also depends on the environment (e.g. water versus membrane).
Amino acid side chains affect the amino acid’s movement.
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For example, Val, Ile, and Thr have a second methyl group branching out of the beta
carbon, creating steric hindrance.
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For example, the chains are arranged differently in alpha helices than in beta sheets.
This strongly determines whether the side chains form beta sheets.
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As another example, Lys can accommodate lots of motion inside its side chain because
it’s a straight carbon chain.
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The ring in Pro locks it into place, so it can’t move at all.
Polypeptides are polymers.
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If the polypeptide is linear, no peptide bonds form to create a branched polymer among
the side chains.
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Cells are able to make peptides enzymatically without ribosomes, however these are
never proteins; proteins come off of ribosomes.
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A protein can have more than one polypeptide chain.
Proteins can be modified in three ways after or during synthesis:
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An amino acid can be chemically modified
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A piece of the protein can be cleaved off
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A non-amino acid group can be added
Molecular weight does not have units, but molecular mass is measured in Daltons (Da).