Lesson 4
Building Blocks of Biochemistry
This week we will go over the main building blocks of biomolecules that are studied in biochemistry or biophysics: nucleic acids, amino acids, fatty acids, and carbohydrates. Nucleic acids make up DNA and RNA, amino acids make up proteins, fatty acids make up lipids, and carbohydrates make up sugars. Our lab focuses on membrane proteins so proteins and lipids are our main interest, but we also need to manipulate the expression of the protein so it is essential that we also understand nucleic acids. We won't focus on carbohydrates here, but they can be added onto protein molecules (such as glycosylation) and can impact their structure and function.
Nucleic Acids
DNA (deoxyribonucleic acid) is made up of four different nucleic acids: adenine (A), thymine (T), guanine (G), and cytosine (C). Each nucleic acid has a sugar-phosphate backbone attached to the differing base. A and G are purines while C and T are pyrimidines. The nucleic acids base pair together (A with T, and G with C) to form a double helix. These base pairs are held together with hydrogen bonds.
RNA (ribonucleic acid) is similar to DNA but it is single stranded and uses uracil (U) instead of thymine (T) and the many of the nucleic acids are modified with additional functional groups. We will learn more next week about how DNA codes for RNA through a process called transcription and RNA codes for protein through a process called translation.
Read this Khan Academy page describing nucleic acids in more detail. Stop when you get to the properties of RNA section.
[1]
Q1: If one strand of DNA has the sequence 5’-CGCATGTAGCGA-3’, what is the sequence of the complementary strand?
For those completing the Summer 2020 tutorial, answer these questions in a shared Google Doc and share it with me by Thursday at 5 pm.
Q2: What intermolecular forces stabilize the DNA double helix? Identify the functional groups on each base that is available and list the type of interaction it can participate in.
Amino Acids
As we already introduced, amino acids make up proteins. We will dive much deeper into the structure and function of proteins in Module 2 and discuss how DNA codes for amino acid sequence in the next lesson.
All amino acids have a common backbone comprised of an amine group (-NH2) and a carboxyl group (-COOH) and a unique side chain (denoted R). There are 21 different amino acids in the genetic code, each with unique side chains. 11 of the amino acids our body can make (called non-essential amino acids) and the other 9 we must get from the food that we eat (called essential amino acids, contrary to the chart below histidine is essential) - one reason to eat a healthy diet.
[2]
Each amino acid has unique properties due to its specific side chain (R group). Some are charged, some polar, and some hydrophobic. As we will learn in lessons to come, these amino acids allow proteins to fold into various conformations and to perform their unique functions.
Explore properties of the different amino acids through this NCBI Amino Acid Explorer. Use the drop down menu in the Structure and Chemistry box to look at different amino acids.
Amino acids combine to form peptide chains. The bonds between the amino acids are called peptide bonds, as shown in red in the figure below.
[3]
Each amino acid, along with their full name, as a three letter abbreviation and a one letter abbreviation. For example, as you can see in the chart below (remember the letters for carbon are not shown and hydrogens on carbon are not shown), arginine has the three letter abbreviation Arg (in parenthesis) and the one letter abbreviation R (in the highlighted circle). Most of the time we use the full name when communicating verbally, and the one letter abbreviation when writing.
[4]
Q3: Using the chart above, determine the amino acid sequence shown below. You can use the one letter abbreviation for each amino acid.
[5]
Q4: One geeky thing we biochemists due is spell out names and things with the structures of amino acids in a peptide chain such that the single amino acid code will spell out the name. Can you spell your name in amino acids?
Q5: Given a specific amino acid in a protein, which of the amino acid mutations (due to changes in DNA sequence) do you think would cause the least change in the protein's structure and function and which do you think would cause the greatest change (biggest difference in molecular interactions based on changes in the functional groups)?
Q5A: Serine mutated to alanine, cysteine, or phenylalanine
Q5B: Arginine mutated to glutamine, aspartic acid, or lysine
Q5C: Histidine mutated to lysine, tyrosine, or phenylalanine
Fatty Acids
Fatty acids are made up of a carboxylic acid and a hydrocarbon chain. Fatty acids combine to form triglycerides, phospholipids, and cholesterol esters. We are most interested in phospholipids because they make up the cell membrane (where membrane proteins are located).
Read the introduction, fatty acids, and phospholipid sections in this article.
Phospholipids are made of a hydrophilic phosphate head group and two hydrophobic fatty acid tails. Phospholipids are thus called amphipathic because they contain both hydrophilic and hydrophobic parts. Phospholipids are named based on the length and saturation of their tails. A few examples are shown below:
Q6: Using what you have learned about molecular interactions, how do you think lipids orient in a cell membrane and why is this orientation favorable?
Saturation is a term which refers to the number of double bounds found in the fatty acid tails. A saturated lipid has no double bounds (such as DLPC, DMPC, and DPPC above) while an unsaturated lipid has one or more double bonds (such as POPC above). The double bound creates a kink in the hydrocarbon chain as can been seen below.
[6]
Q7: How do you think the presence of the double bounds in unsaturated lipids impacts membrane fluidity (the ability of the lipids to move within the membrane)?
[1] "File:Building nucleic acids SVG.svg" by Biochemlife is licensed under CC BY-SA 4.0
[2] "File:Unionized Alpha Amino Acid Structure.svg" by Scott Henry Maxwell is licensed under CC BY-SA 4.0
[3] "File:SIMPLIFIED PEPTIDE CHAIN.png" by شہاب is licensed under CC BY-SA 4.0
[4] "File:Amino Acids002.svg" by Pk0001 is licensed under CC BY-SA 4.0
[5] "File:MOTS-C.png" by BQUB17-JHolguera is licensed under CC BY-SA 4.0
[6] "File:0301 Phospholipid Structure.jpg" by OpenStax is licensed under CC BY 4.0