Lecture: Biological Macromolecules
Lecture script · about 15–20 minutes spoken · Week 3
Opening
Put a plain cracker on your tongue and chew it slowly. At first it tastes like flour and salt. Keep chewing, and it starts to taste a little sweet. Nobody added sugar. Something in your mouth changed the cracker while you chewed. By the end of this lecture, you'll know exactly what happened.
These molecules show up wherever you go. A nursing student meets them when one changed amino acid causes sickle cell disease. A home cook meets them when an egg white turns solid in a hot pan. A shopper meets them on every nutrition label, in the lines for carbohydrate, fat, and protein. Underneath all three is the same small set of large molecules.
In Week 1 you learned to test a claim against a control. In Week 2 you met atoms, bonds, water, and pH. In this lecture we put those pieces together into the big molecules of life. I'll show you how cells build long chains and break them with water. Then we'll sort the four classes, and I'll take you through carbohydrates, lipids, proteins, and nucleic acids one at a time. We'll watch one amino acid change a whole protein. Last, we'll read an iodine test that shows the idea this whole course rests on. Next week, in Week 4, these molecules go to work inside the cell.
1. Building and breaking chains with water
Think about a string of paper clips. Each clip is one small unit. Hook enough of them together and you get a long chain. Unhook them, and you're back to single clips. Your cells build their largest molecules in the same way.
Here are the words. A monomer is one small building-block unit that can be joined to others like it to make a larger molecule, such as a glucose unit or an amino acid. A polymer is a long chain of monomers joined by bonds, such as starch, a protein, or a strand of DNA.
Now the surprise. Water is part of both building and breaking. Dehydration synthesis is the reaction that builds a polymer by joining two monomers and removing one water molecule for each new bond. "Dehydration" means losing water. Hydrolysis is the reaction that breaks a polymer apart by adding a water molecule back across a bond. "Hydro" means water, and "lysis" means splitting.
Let's count. Take 3 glucose units in a row. Between neighbors there's one bond, so 3 units have 3 minus 1, which is 2 bonds. Building that chain removes 2 water molecules, one per bond. Breaking it with hydrolysis adds the same 2 water molecules back.
And now the cracker. Digestion is hydrolysis. The cracker is full of starch, a long chain of glucose. Chewing turns it sweet because amylase in your saliva hydrolyzes starch toward maltose and glucose. The chain gets cut at its bonds, with water added at each cut, and the smaller sugars taste sweet.
Pause and try this. A classmate says, "Hydrolysis is how cells build a polymer." Which word in that sentence needs to change?
Think about which way the water moves.
Here's the answer. "Build" should be "break." Hydrolysis adds water and breaks a polymer apart, while dehydration synthesis removes water and builds one.
Hold on to this line: build by removing water; break by adding water.
2. Four classes of large molecules
Picture the nutrition label on a granola bar. It lists carbohydrate, fat, and protein. That label names three of the four classes of big molecules in one glance. The fourth class is in the food too, inside every cell of the oats and nuts. Labels don't list it.
A macromolecule is a large biological molecule; living things build four classes of them: carbohydrates, lipids, proteins, and nucleic acids. Each class has its own building block and its own jobs. Carbohydrates are built from single sugar units. Proteins are built from amino acids. Nucleic acids are built from nucleotides. And lipids, as you'll see in a minute, are the odd one out.
Here's something worth noticing. A bacterium, an oak tree, and you all build yourselves from these same four classes. In Week 1, that shared set of building-block molecules was one piece of evidence that all living things descend from common ancestors. You're looking at that evidence on a snack label.
The fastest way to sort a molecule is to ask one question: what is it built from? The building block names the class.
Pause and try this. Glycogen, olive oil, an enzyme, and a strand of DNA. Which class does each one belong to?
Ask what each one is built from.
Here's the answer. Glycogen is a chain of sugar units, so it's a carbohydrate. Olive oil is a lipid, an enzyme is a protein, and DNA is a nucleic acid.
3. Carbohydrates: one sugar to many
Think about three foods: a spoonful of table sugar, a baked potato, and the fiber listed on a cereal box. All three are carbohydrate. Only the sugar tastes sweet. The difference is in how the sugar units are joined.
A carbohydrate is the class of macromolecules made of sugar units, from single sugars such as glucose to long chains such as starch and cellulose. Picture a ladder with three rungs. A monosaccharide is a single sugar unit, such as glucose. A disaccharide is a sugar made of two sugar units joined together, such as table sugar, which is sucrose. A polysaccharide is a carbohydrate made of many sugar units joined in a chain, such as starch or cellulose.
Now here's the part I want you to see coming. Starch is a polysaccharide built from glucose that plants use as stored fuel. Cellulose is a polysaccharide built from glucose linked differently from starch, which gives plants structural fiber and is the dietary fiber in food. Same monomer. Different links. And that difference in linking changes the shape of the whole chain, so it changes the job. Starch coils and serves as fuel. Cellulose forms tough fiber.
Think of the same pile of bricks. Laid one way, they make a round oven. Laid another way, they make a straight wall. Same bricks, different arrangement, different use.
Pause and try this. Someone says, "All carbs are sugar." How would cellulose answer that?
Think about the fiber line on the cereal box.
Here's the answer. Cellulose is a carbohydrate, and it's the dietary fiber, not a sugar you taste. Sugar is only the bottom two rungs of the ladder.
4. Lipids, the class that isn't a chain
Leave a stick of butter and a bottle of cooking oil on a cool counter. The butter stays a solid block. The oil pours. Both are mostly fat, and neither dissolves in water. So why is one solid and one liquid?
A lipid is the class of macromolecules grouped by being water-fearing rather than by a repeating monomer, including fats and oils, phospholipids, and steroids. Lipids are not polymers. That's the big idea of this section.
Start with fats and oils. A triglyceride is a fat or an oil, assembled from one glycerol and three fatty acids rather than from a chain of one repeating monomer. Picture a capital letter E. The upright stroke is the glycerol, and the three arms are the fatty-acid tails. That's 1 plus 3, or 4 parts, and they're two different kinds of molecule. So it's an assembly, not a chain.
The tails decide solid or liquid. A saturated fatty acid has only single carbon-carbon bonds, and its straight tail packs tightly, so fats made of such tails stay solid. An unsaturated fatty acid has at least one carbon-carbon double bond that puts a kink in its tail, so fats made of such tails stay liquid. Straight tails stack like pencils in a box. Kinked tails jostle like bent sticks and can't pack close.
Two more lipids. A phospholipid is a lipid with a water-loving, phosphate-containing head and two water-fearing fatty-acid tails. One end likes water and the other avoids it, and that split is the reason a membrane can exist. You'll see that membrane next week. A steroid is a lipid built on four fused carbon rings, such as cholesterol.
Pause and try this. A study guide says, "Lipids are polymers, like the other three classes." What would you correct?
Think about the capital letter E.
Here's the answer. Lipids aren't polymers. A triglyceride is one glycerol plus three fatty acids, an assembly of a few parts, and a steroid is four rings with no chain at all.
5. Proteins and their four levels
Picture an egg white in a hot pan. It starts clear and runny. Soon it turns solid and white, and cooling it never turns it back. Egg white carries a protein called albumin, and the heat changed that protein's shape. To see why shape matters so much, let's build a protein.
A protein is the class of macromolecules built from amino acids joined by peptide bonds. An amino acid is the monomer of proteins, and cells build proteins from 20 common kinds. Proteins do a long list of jobs: enzymes, structure, transport, defense, and signaling.
A chain of amino acids doesn't stay a floppy string. It folds, and we describe the folding in four levels, always in this order. Primary structure is the exact order of amino acids in the chain. Secondary structure is the local coils and folds of the chain, the helix and the pleated sheet, held by hydrogen bonds. Tertiary structure is the overall three-dimensional fold of one complete chain. Quaternary structure is two or more folded chains assembled into one working protein. Sequence, coil, fold, assemble.
Now back to the egg. Denaturation is the loss of a protein's three-dimensional shape, and with it its function, caused by heat, a change in pH, or certain chemicals; the amino-acid sequence stays intact. The heat undid the fold. It didn't cut the chain.
Pause and try this. After the egg white turns solid, which level of protein structure is still there?
Think about what heat undoes and what it leaves alone.
Here's the answer. The primary structure, the sequence, is still there. Denaturation loses the shape and the job, but the chain of amino acids stays intact.
6. One amino acid, one changed job
Think of a sentence where one letter changes: "the cat sat" becomes "the cot sat." One letter, and the meaning shifts. A protein can do the same thing.
Hemoglobin is the protein packed inside your red blood cells. Sickle cell disease is a disease in which valine takes the place of glutamic acid at position 6 of hemoglobin's beta chain. That's one change out of roughly 600 amino acids, counting all four chains.
Follow that one change upward. In the primary structure, valine sits where glutamic acid should be. The altered hemoglobin links into long fibers when oxygen is low. Those fibers bend the red blood cell into a rigid crescent, the sickle shape. And rigid crescent cells can block small blood vessels. One amino acid in about 600, and the change ran all the way up from a sequence to the shape of a whole cell.
That's why I keep saying the order is the information. Change one amino acid, and the fold can change. Change the fold, and the job can break.
Pause and try this. A friend says, "One amino acid out of hundreds can't matter much." What example answers that?
Think about position 6.
Here's the answer. Sickle cell disease answers it. Valine in place of glutamic acid at position 6 of the beta chain changes how hemoglobin behaves and bends red blood cells out of shape.
7. DNA and RNA
Picture a master recipe book kept safely on a shelf, and a single recipe card copied out to use at the stove. The book is the complete store. The card is a working copy. The two nucleic acids split their work in a similar way.
A nucleic acid is the class of macromolecules, DNA and RNA, built from nucleotides, which store and pass on a cell's instructions. A nucleotide is the monomer of nucleic acids, made of a sugar, a phosphate, and a base.
There are three differences you can check. DNA has the sugar deoxyribose and the bases adenine, thymine, guanine, and cytosine, and it's usually built as a two-stranded double helix. RNA has the sugar ribose, uses uracil where DNA uses thymine, and is usually a single strand. So check the sugar, check the base, and count the strands.
For now, one sentence is all we need about what the bases do: the base sequence is a code for the amino-acid sequence. How a cell reads that code comes much later in the course.
Pause and try this. You see a single strand that contains thymine. Is the label "RNA" right?
Check the base first.
Here's the answer. No. Thymine belongs to DNA, and RNA uses uracil in its place. A T in RNA means something has gone wrong.
8. Reading the iodine test: structure determines function
Set five small dishes on a kitchen counter: bread, a slice of raw potato, sugar water, cooking oil, and a slice of fruit. Add a sixth dish of plain water. Now put a drop of iodine on each one.
Iodine starts amber, an orange-brown color. When it meets starch, it turns blue-black, because iodine fits inside the coiled starch chain. That means the test is reading a shape. These results are illustrative, a qualitative set built for this course, not real data.
First, the control. A negative control is a sample known to lack what a test detects, such as plain water in an iodine starch test, which shows the color a no result should give. Plain water stays amber. You compare every food against it, the same control habit from Week 1.
Now read the dishes. Bread turns blue-black, so starch is present. Potato turns blue-black too. Sugar water stays amber, because table sugar is a disaccharide, not a polysaccharide, so iodine cannot detect it; finding the sugar would take a different test. Cooking oil stays amber, because oil is a lipid. Fruit stays amber or changes faintly, so there's little free starch. That's 2 of the 5 foods blue-black, 2 amber, and 1 faint, which adds up to 5.
Here's the idea underneath. Structure determines function is the principle that the shape of a molecule, cell, or organ decides what job it can do, so a change in shape can change or break the job. You saw it with starch and cellulose, with straight and kinked tails, with the egg white, and with hemoglobin. Now you see it in a dish of iodine.
Pause and try this. Someone predicts the sugar water will turn blue-black because it's so sweet. What does the test show, and why?
Remember what iodine is reading.
Here's the answer. The sugar water stays amber. Iodine reads starch's coiled shape, not sweetness, and sucrose is a two-unit sugar with no coil to fit inside.
Closing
Let me pull it together. Cells build polymers by dehydration synthesis, removing water, and break them by hydrolysis, adding water back. Life runs on four classes of large molecules, and you sort them by asking what each is built from. Starch and cellulose share glucose but differ in their links, and so in their jobs. Lipids are not polymers, and the shape of a fat's tails decides solid or liquid. Proteins are built from 20 common amino acids and fold in four levels, and denaturation loses the shape but keeps the sequence. One amino acid at position 6 of hemoglobin's beta chain shows how much the order matters. DNA and RNA differ in sugar, base, and strands. And the iodine test shows the spine of this course: structure determines function.
Next in this module come the slide deck, the Readings & Resources page, the lecture tutorial, the practice set, and the quiz. Then comes the Biology Lab & Inquiry, where you'll run the starch test on your own foods. Next week, in Week 4, Cell Structure & Function, the phospholipid becomes a membrane, and these molecules go to work inside the cell.
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