Download worksheet 7 – lipids chem 240 1 1. Lipases are enzymes that

worksheet 7 – lipids
chem 240
1. Lipases are enzymes that degrade fatty acids. An example of a fatty acid is palmitic
acid (CH3(CH2)14COOH).
a) If the following amino acids (Val, Ser, Asp, Lys, Ile) were in the lipase active site,
which ones would be important for the binding of palmitic acid? In your answer, draw
out the substrate and any of these amino acids you think are important for binding.
Support your answer by specifically drawing the noncovalent force that each side chain is
providing for binding to the substrate. You do not need to draw the structures for the
amino acids, but you need to provide any key characteristics that are important for the
noncovalent force to occur.
b) If the above Lys were mutated to a Glu would the substrate binding be tighter, weaker,
or not be affected? Clearly support your answer. How would this mutation affect the
tightness of the binding in the enzyme-substrate complex?
So much to talk about here, so little time……
The main points are that lipase is an enzyme, plamitic acid is a substrate for this enzyme,
and you want to create an active site within this enzyme for binding this substrate.
a) The substrate, palmitic acid has a long hydrocarbon chain and a carboxylic acid
(which will be neutral at physiological pH). So, we need to decide which amino acids
will be in the active site of lipase to help bind this substrate. Our choices are Val, Ser,
Asp, Lys, and Ile. ALL interactions that are involved in forming an E●S complex will be
noncovalent.
If we want to think about interactions with the nonpolar tail of the substrate (which do not
actually occur but we are not told that information in terms of this question) we would
have to stick with all nonpolar amino acids for van der Waals interactions. So, these
would be Val and Ile.
The stronger interactions would actually be between the polar sections of the substrate
and polar amino acids in the active site. The carboxylic acid has the ability to accept and
donate to hydrogen bonds. The amino acids that could be involved in these interactions
would be Ser, Asp, and Lys. You might draw an H-bond from Ser (H donor) to the
carbonyl oxygen on palmitic acid, for example.
Even stronger noncovalent interactions would occur between the dipole on the substrate
molecule and a full charge on amino acids within the active site. Remembering that the
carboxylic acid will have a partial negative charge, I would think that an amino acid with
a full positive charge would form the strongest bond to the substrate. So, I would choose
Lys. Likewise, an amino acid with a full negative charge might actually be destabilizing,
so I would opt not to put Asp in the active site.
b) Just like the last part of (a) above, changing Lys (with a positive charge) to Glu (with a
negative charge) should destabilize the interaction between the enzyme and substrate.
Substrate binding would thus be weaker.
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worksheet 7 – lipids
chem 240
2. Consider the physical properties of glycogen and a triacylglyceride.
(a) On a per-weight basis, which is a more efficient form of energy storage, fat or
glycogen? Explain your answer in biochemical terms.
(b) On a carbon per carbon basis which contains more stored energy, a fatty acid or a
carbohydrate? Explain your answer in clear biochemical terminology.
(a) Glycogen is a sugar with polar OH groups on it. Therefore, it will form hydrogen
bonds to water. Fat, on the other hand, is relatively water insoluble. This means that if
you weighed out the same amount of glycogen and fat, the glycogen would also contain
water molecules, so overall, would have less energy per gram. So fat is a more efficient
storage form than glycogen.
(b) For the same number of carbon atoms, a fatty acid is more highly reduced than a
carbohydrate. Since energy is released during metabolism through oxidation reactions, if
you start with a more reduced sample, you can go through more oxidation reactions and
therefore release more energy. So, the fatty acid contains more stored energy on a carbon
per carbon basis.
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