AP Biology Nucleic Acids and Proteins

Welcome to Educator.com.0000

We are going to continue our discussion of large biological molecules with a lesson on nucleic acids and proteins.0002

In the previous lecture, we talked about two other classes of large biological molecules- carbohydrates and lipids.0010

I also introduced some basic sub-organic chemistry there, so if you have not watched that lecture yet,0017

and you are not familiar with organic chemistry, you may want to watch at least the first part of that before going on to this.0022

There are two types of nucleic acids: DNA/deoxyribonucleic acid and ribonucleic acid.0030

DNA contains an organism's genetic information, and that information is passed on from parents to offspring.0037

DNA codes for proteins.0045

In the molecular biology section, we will talk about how DNA is synthesized, how the DNA is transcribed into RNA, and how that RNA is translated into a protein.0048

Right now, we are just focusing on the structure of both DNA and RNA.0062

DNA is made up of nucleotides. These are the building blocks for the DNA molecules.0068

RNA, same thing, it is made up of monomers of nucleotides, so let's go ahead and look at the nucleotide structure.0078

There are three parts: there is a sugar; there is a nitrogenous space; and there is a phosphate group.0087

In both DNA and RNA, the sugars are 5-carbon sugars, so these are pentoses.0096

However, the sugar in DNA is deoxyribose, whereas RNA contains ribose, so the name explains the difference.0102

Deoxyribose is missing one of the oxygens, so ribose has a hydroxyl group here, whereas DNA just has a hydrogen.0111

That is one difference between DNA and RNA although their fundamental structure is the same.0124

DNA and RNA both have nitrogenous bases attached to the sugars, and there are five different types of nitrogenous spaces that we will look at in the next slide.0131

If you just consider the nitrogenous base plus the sugar in either DNA or RNA, that is called the nucleoside.0147

With the phosphate group added, you have a nucleotide.0158

These nucleotides are the monomers from which the larger DNA or RNA molecule are formed.0168

Here, are shown the five different nitrogenous bases, and they can be classed into two groups.0182

These first two are more complex. They have a 6-membered ring fused to a 5-membered ring, and these are known as purines.0192

These top two are purines, and there are two.0202

Adenine, it is often known by its abbreviation A and quinine known by just the letter G.0205

Here, below in this row, are the pyrimidines. They are based on this 6-membered ring.0213

And these are rings that contain carbon and nitrogen, and there are three pyrimidines: cytosine, thiamine and uracil.0221

One important thing to know is that thiamine is found only in DNA, whereas uracil is found only in RNA.0231

In lieu of thiamine, RNA has uracil, otherwise, DNA and RNA have the same nitrogenous bases.0245

A, G and C are found in both DNA and RNA, thiamine only in DNA, uracil only in RNA.0255

One thing also to keep in mind as you are looking at structures of RNA and DNA is that in order to distinguish the carbons0262

on the nitrogenous bases from the atoms on a sugar, the atoms on the sugars - ribose and deoxyribose - have a prime after them.0272

So, we will sometimes be referring to the 2-prime or the 3-prime carbon, and those refer to the different atoms on the sugar.0282

These prime means that we are talking about the atom on the sugar versus an atom on these nitrogenous bases.0292

Nucleotides join to form polymers that consist of a sugar phosphate backbone with the attached nitrogenous bases.0301

One nucleotide is linked to the next nucleotide to form what is called a polynucleotide.0310

The monomers are the nucleotides, and they join to form polynucleotides; and that is usually what we are talking about when we talk about DNA and RNA.0317

The linkage that attaches these is known as a phosphodiester linkage.0326

Remember, when you just looked at the monomers, each one of them had a sugar, a nitrogenous base and a phosphate group.0342

And the phosphate groups serve as the linkage between one monomer and the next monomer.0348

We are going to talk about this synthesis in detail in the molecular biology lecture, but for right now, you should be aware that there is a directionality to DNA.0357

And we discussed DNA and RNA as having 5-prime ends and 3-prime ends.0365

The 5-prime carbon on what we call the 5-prime end of the polynucleotide has a phosphate group attached, so this is the 5-prime end.0375

There is a phosphate group attached to the 5-prime carbon.0385

This end is called the 3-prime end, so there is this three hydroxyl group.0392

Here, we have this phosphate group to 5-prime end, and then, we have the hydroxyl group attached to a 3-prime carbon on the 3-prime end.0400

This directionality is very important because synthesis of DNA always occurs 5-prime to 3-prime.0409

And again, we will get into the details of that later, but right now, you should just know the basics that there is a 5-prime end. There is a 3-prime end.0417

Two adjacent nucleotides are linked via a phosphodiester linkage.0424

And you should also be aware that this section, the sugar and the phosphate group, are known as the sugar-phosphate backbone,0430

so, sugar-phosphate backbone right here and then, attached nitrogenous bases.0442

The order of these nitrogenous bases is the genetic code.0452

You could have a strand of DNA that may have a nitrogenous base A attached. The next one is G, then another G, C, T.0458

And it is these bases, it is the order of those bases, that encodes the information to make a protein.0468

And it is this information, this order of the bases, that is passed along from parent to offspring.0475

DNA is found in a double helix structure. This double helix structure is formed by two complimentary strands.0483

These strands are also anti-parallel, so what do we mean by anti-parallel? Well, it has to do with that directionality.0491

Let's say that this is the 5-prime end of one of these pieces of DNA, and we follow this down; and it is going to end here at the 3-prime end.0501

The other strand is going to have the opposite orientation where it starts with the 3-prime end up here and then, ends at the 5-prime end down here.0512

So, we say that these two strands are anti-parallel. They are complimentary, and they are anti-parallel.0522

The 5-prime to 3-prime versus 3-prime to 5-prime explains the anti-parallel.0532

What does complimentary mean? Well that has to do with what is called base pairing.0538

Remember that in DNA, there is no uracil used. We have A, G, C and T.0542

Adenine pairs with thiamine, and this would be called a base pair; and G/guanine pairs with cytosine.0553

Here is a sugar-phosphate backbone shown with a purple.0572

And then, the nitrogenous bases A, G, C and T actually stick inward towards the center, towards the middle of this double helix.0575

This double helix structure was actually a famous discovery by Watson and Crick in the 1950s.0594

And, we have the sugar-phosphate backbone, and then, let's say this nitrogenous base here is A and T, C, G, A, T.0600

Since A pairs with T, this complimentary strand is going to have a T.0619

T pairs with A. The complimentary strand will have a an A.0624

C is going to pair up with G, so you are going to have a G here.0627

G, C, A pairs up with T. T pairs up with A and so on.0635

Complimentary refers to the fact that the base pair on the second strand matches with the base on the first strand.0643

Now, hydrogen bonding occurs between these base pairs, and that is what holds this helix in its structure.0655

And you will notice up here that I showed three dotted lines between G and C, whereas there is only two dotted lines between A and T.0663

And that is because A-T forms two hydrogen bonds with each other, whereas G and C form three hydrogen bonds with each other.0671

OK, important place to remember is that DNA is a 5-prime end, a 3-prime end.0681

Nucleotides are linked by a phosphodiester linkage.0686

Their structure is such that there is a DNA double helix that is formed between two complimentary anti-parallel strands.0691

Each strand is paired so that it has a matching base pair.0702

A always pairs with T. G always pairs with C.0709

And these nitrogenous bases, these base pairs, form hydrogen bonds that keep this double helix structure in place.0714

RNA is single-stranded.0723

In biology, form follows function, and you will see how this double helix is very important0731

in the synthesis of DNA and in producing DNA that has as few mistakes as possible, so that genetic mistakes or mutations are not introduced.0735

We will revisit this double helix structure later on with a focus on DNA synthesis, transcription and translation.0744

The next large biomolecule that we will talk about is proteins.0755

Amino acids are the building blocks of proteins, and these join to form polypeptides.0759

So, remember that DNA contain genes, and these genes encode proteins.0765

Proteins are extremely important to living organisms because they make up structural elements such as our muscles.0773

They facilitate reactions in the form of enzymes, which we will discuss later.0781

They are involved in cell signalling. They are involved in cell growth and the repair of cells, so proteins are fundamental to life.0785

There are twenty main or common amino acids.0792

You do not have to know each of these. You just need to know the general structure of amino acids and some different classifications of the amino acids.0797

Let's look at just a generalized amino acid. You are going to see that it has certain groups.0805

Here, it has an amino group. On the other side, it has a carboxyl group.0810

In the center is a carbon atom, so bonded to the carboxyl group, the amino group, a hydrogen and then, what we call an R-group.0821

The R-groups are different, so each of the twenty amino acids has a different R-group.0830

It could be as simple as just hydrogen. That would be just glycine, structurally the simplest amino acid.0836

Or it could have more complex functional group like shown here with asparagine or even more complex than that.0839

You might see amino acids also written instead of NH₂, you might see this shown as NH₃⁺ and the carboxyl group as COO^-.0852

And that is because in water, the amino group picks up a hydrogen ion and, therefore, acts as a base.0862

And that carboxyl group loses a hydrogen ion and, therefore, acts as an acid.0871

You are also going to notice that there are 3-letter abbreviations for the amino acids, so you might see instead of asparagine written out, Asn.0880

Or for example, leucine is another amino acid that is abbreviated as Leu and glutamine, Gln.0888

There are also 1-letter abbreviations for the amino acids.0896

Let's talk a little bit more about these side chains. The side chains can be grouped such that they are non-polar, they are polar, they are acidic, or they are basic.0900

First, let's just talk about non-polar.0926

Glycine has an R-group that is just a hydrogen atom. That is going to be an example of a non-polar amino acid.0929

A polar amino acid might have, for example, hydroxyl groups on it or some other polar functional groups.0941

Asparagine is actually considered a polar amino acid, so this one is polar.0950

Acidic and basic are a little bit more complicated.0957

When we talk about acidic or basic amino acids, we are not talking about the amino group here or the carboxyl group here.0960

We are talking about the R-group or the side chain.0966

If you think about it, in a solution, this is going to pick up a hydrogen ion. This is going to lose one.0970

They are going to essentially neutralize each other.0974

So, the amino acids overall, in the different forms that they are in in solution. If they are not, it is going to be that they are neutral.0976

However, if there is a carboxyl group on the side chain, if the side chain has a carboxyl group, then, you would have an acidic amino acid.0985

If the side chain contains an amino group, then, you would have a basic amino acid.0998

Again, we are not looking at this. When we talk about polar or non-polar amino acids, we are talking just about what is going on with the side chain.1008

I want to point this out. This is a bit of an exception.1015

Glutamine and asparagine are both polar. They are not basic.1020

Even though you see this NH₂ here, and you might think "oh, an amino group".1027

This particular construction, where you have C double bonded to O, linked to NH₂, is something called an amide group.1030

And this is a bit different. It is not actually basic.1039

If you had this NH₂ but it was not linked to the C double bond O, then, I would say "OK, you have a basic amino acid".1044

But this particular group together actually is not a basic side chain.1049

Glutamine has this group. Asparagine has this group.1055

These two are classed as polar, not as basic.1058

Aspartic acid is a good example of an acidic amino acid. The side chain contains COOH, this carboxyl group and that cellular pH.1063

This becomes ionized to COO^-, and therefore, this is an acidic amino acid. It tells you so in its name.1079

OK, we talked about amino acids. These are the building blocks for proteins.1089

Amino acids can be joined together to the formation that is called a peptide bond.1095

A peptide bond is yet another dehydration reaction.1101

We discussed that in previous lecture where a dehydration reaction is a reaction where water is removed, so we lose a water.1104

Recall that the basic structure of an amino acid would be NH₂, central carbon, an R-group, hydrogen, and then, we have this carboxyl group, COOH.1115

An adjacent amino acid would have the same structure, so now, we are just going to do COOH over here, R here.1139

Here, we have the NH₂, and here we have H; so, let's write this as NHH1150

This peptide formation, again, is through a dehydration reaction, so water is going to be lost.1163

So, if an OH is removed from here, and then, H is removed from here, you are going to end up with H₂O removed.1169

And that will leave this CO, which is this, becomes double bond, and this nitrogen, which is here, bonded together.1179

This carbon from the carboxyl group bonds to the nitrogen from the amino group, and water is lost.1189

Again, COOH and NH₂, loss of an OH group from the carboxyl, a hydrogen from the amino group, leaving behind C double bonded to O.1195

And then, the C bonds to the nitrogen and then adjacent amino acid forming a peptide bond.1206

What is shown here is a dipeptide. It is two amino acids.1213

Three or more amino acids are a polypeptide chain, and a polypeptide chain can be very short, just a few amino acids.1216

It can be a thousand amino acids long.1223

The primary structure of a protein is the amino acid sequence of its polypeptide chain.1226

There are multiple levels of structure in a protein. There are three to four depending on the type of protein: primary, secondary, tertiary and quaternary.1233

The primary structure is just the order of the amino acids if it is leucine and glycine, glutamic acid, then another asparagine, another asparagine.1242

That would be giving the primary structure of the protein.1252

Now, polypeptides are not the same as proteins. Polypeptides are just chains of amino acids.1259

They are in a particular order, but if they are unfolded, they are just chains- they are polypeptides.1268

In order to actually be protein, a polypeptide chain or chains - sometimes there is more than one chain in the protein - need to be folded1273

in a unique 3-dimensional conformation, then, that is a protein.1280

Once you just have bunch of amino acids linked, it is not a protein yet. It is a protein once it is folded.1285

The primary structure is actually what determines this folding, although nobody is quite sure how.1291

And the primary structure of a protein was first elucidated by Fred Sanger at Cambridge, and he and his lab actually sequenced insulin.1298

Remember that insulin is a hormone secreted by the pancreas, and it is vital in controlling glucose levels in the bloodstream.1308

Without enough insulin, a person becomes diabetic.1315

Another medical example of the importance of the primary structure of protein is the disease sickle-cell anemia.1317

This disease is caused by the substitution of a single amino acid- valine.1327

Instead of valine, it is actually, valine is substituted for glutamic acid, so valine substitution.1334

That change of that one amino acid to a different amino acid causes problems in the structure of hemoglobin.1347

Hemoglobin is found in red blood cells. It carries oxygen.1355

The structure of the hemoglobin is abnormal in people with sickle-cell anemia, and the result is that it actually causes the red blood cells to form a sickle shape.1359

And those sickle-shaped cells tend to clump up.1367

Red blood cells are normally a biconcave disk. They move nicely through even small vessels like capillaries.1373

With sickle-cell anemia, these cells form a sickle shape. They clump up, and that causes poor circulation to various parts of the body and symptoms.1379

The primary structure of a protein is very important in determining the secondary and tertiary structure and the function of the protein.1388

So, we went to this first level of structure. Let's go into more detail about the other levels1397

The secondary structure of a protein is the result of hydrogen bonding between different regions of the polypeptide backbone.1402

When I say polypeptide backbone, that means not the side chain. It means the other parts.1409

The two main protein secondary structures are alpha-helices and beta-pleated sheets, so let's go back to how these are formed.1415

There are certain regions on a polypeptide strand that are repeated, and particular repeated regions allow for hydrogen bondings.1424

This bonding occurs between the electronegative oxygen atoms and the hydrogen atoms attached to the nitrogen.1434

So, remember your basic amino structure. There is an R-group.1450

There is a carboxyl group. There is hydrogen, and there is an amino group.1454

And the hydrogen on the amino group is attracted to the electronegative oxygen atoms in these carboxyl groups.1460

This would cause hydrogen bonding between one amino acid and another nearby amino acid.1468

We are not talking about the side chains. We are just talking about the backbone structure, which is this part.1475

The electronegative oxygen and a hydrogen atom attached to a nitrogen can form hydrogen bonds.1482

If there are certain repeated regions, particular types of repeated regions, you can end up with either this helix shape - it is like a spiral -1491

or what is called a beta-pleated sheet, and it is like if you took a piece of paper or something and folded it up.1503

So, this is the alpha-helix and beta-pleated sheet.1509

The important thing to remember about secondary structure is that the hydrogen bonding is between the polypeptide backbones, not the side chains.1521

And that the two main types of secondary structures are alpha-helices and beta-pleated sheets.1528

Again, one hydrogen bond is not that strong, but many hydrogen bonds together could hold the structure in place and stabilize it.1534

The next level of structure is tertiary structure, and tertiary structure is the overall 3-dimensional shape of the protein.1545

This shows a protein that might be described as a globular protein. It is shaped like a globe.1554

An example would be hemoglobin.1561

Within this overall 3-dimentional or tertiary structure, certain regions may have an alpha-helix.1568

Maybe this region over here is beta-pleated sheet, and this is beta-pleated sheet; and this is neither.1575

And then, there is another alpha-helix here and here.1582

The entire polypeptide does not usually form one big alpha-helix or beta-pleated sheet.1585

Often, there is just little regions of each in certain areas of the protein, and then, those regions, along with the rest of the protein, fold into a unique shape.1591

And the shape is extremely important to the protein's function.1603

When we talk about enzymes, you will see that the shape of the enzyme is crucial in it being able to facilitate a reaction.1606

There are five types of interactions that form and maintain the tertiary structure.1617

The first one is hydrogen bonding, but this time, it is of those side groups.1630

Remember that hydrogen bonding between a main polypeptide backbone will form secondary structures such as alpha-helices and beta-pleated sheets.1640

Those amino acids that contain hydroxyl groups or amino groups, for example, can hydrogen bond and help to stabilize the 3-dimensional structure.1648

The second type of bond is ionic bonds.1662

Remember that there are certain charged side groups.1665

We talked about the fact that there are some amino acids that are acidic and some that are basic.1670

So, those are charged, and they can form ionic bonds with each other.1675

The third type is known as a disulfide bridge.1679

Cysteine is an amino acid that contains SH on its side chain.1688

Two cysteine molecules can each lose a hydrogen and form what is called a disulfide bridge or bonds.1694

If I have two cyteins near each other, and they each lose a hydrogen; and they form this disulfide bridge or disulfide bond.1705

And this is a covalent bond, but it is still a crucial in forming the tertiary structure.1712

The fourth type is hydrophobic interactions, and what this refers to is that non-polar or amino acids with1719

non-polar side chains often end up clustered in the central part or in the middle of the protein structure.1732

And this is because those amino acids that have polar side chains can form hydrogen bonds with water.1740

So, when proteins are in a solution, the side chains that are polar interact with the water molecules.1746

They form hydrogen, and then, the non-polar ones pretty much just end up excluded from that and pushed to the center.1752

And when these non-polar ones are near each other, they can form various bonds and non-polar interactions.1758

There is one type of interaction between non-polar molecules that are called Van der Waal reactions.1765

These are another type of weak bond, and these form between non-polar molecules.1774

Again, the tertiary structure is the overall shape of the protein. It involves bending and folding.1781

And there are five types of interactions that form and maintain the tertiary structure: hydrogen bonding between the side groups,1787

ionic bonds between side groups that are charged, disulfide bridges between cysteine molecules, hydrophobic interactions, and finally, Van der Waals interactions.1796

There is one final level of structure only for certain proteins, and this is quaternary structure.1807

There are certain proteins that are formed from more than one polypeptide chain.1813

And the interaction between multiple chains in a multi-subunit protein is known as quaternary structure.1817

An excellent example is hemoglobin. Hemoglobin has four polypeptide chains that form the four sub-units of hemoglobin.1823

And not only does each of these chains have a certain tertiary structure,1833

but all four of the chains come together in an overall structure known as a quaternary structure.1837

When you think about protein folding, you need to be aware that certain conditions affect folding.1844

There is an optimal temperature for the folding of proteins. There is an optimal pH and osmolarity or salts concentration.1849

If for example temperature is changed, if a protein is heated up, it melts or unfolds, and we call this "denatures".1861

When a protein denatures, it means that it unfolds.1871

If the pH is changed, if you take a solution and add a bunch of salt to it, the proteins in it could also denature.1875

Proteins function optimally at certain conditions depending on that protein.1882

Like in our bodies, the pH, most areas of our body is about 7.4, so most of the proteins in our body function best at that pH and at our body temperature.1888

If a protein denatures, since formed for all those function, it is not going to function very well.1898

Now, let's go ahead and review some examples focusing on nucleic acids and proteins.1905

Write the complimentary strand for a strand of DNA with the following sequence.1911

Alright, this shows the 5-prime end and the 3-prime end, and then, it shows a sequence G-C-C-A-G-T-T-C-A-A-G for DNA, so, this is at different nitrogenous bases.1917

The first thing in a question like this is to remember that the two strands are anti-parallel.1932

So, right away, as part of the answer, you should always write in the 3-prime and the 5-prime, and they are going to be opposite because it is anti-parallel.1936

The strand is going to be anti-parallel and complimentary.1944

Remember that G forms three hydrogen bonds with C, and A forms two hydrogen bonds with T; so these are the ones that pair up.1948

Therefore, when there is a G, it is going to pair up with the C. A C will pair up with the G, again, with the G.1960

Here, I have an A. It pairs with T.1967

G pairs with C. 2 Ts, these each pair with A.1970

C pairs with G. As pair with T and finally, G and C, so the complimentary strand is going to be 3-prime to 5-prime.1975

The Gs will be paired with Cs. Cs will be paired with Gs.1985

A and T go together and T and A.1989

This is the complimentary strand for this strand of DNA.1993

Example 2: list two differences between DNA and RNA.2001

Well, recall that RNA contains uracil. DNA contains thiamine- that is one difference.2006

Second difference: RNA is single-stranded. DNA is double-stranded.2023

And they only ask for two, but the third difference is that the sugar for RNA is ribose, whereas the sugar for DNA is deoxyribose.2040

Here is three differences. Any two would have sufficed to answer the question: difference in nitrogenous bases,2061

single versus double-stranded and ribose sugar versus deoxyribose sugar.2067

Is each of the following amino acids polar, non-polar, acidic or basic?2076

To determine that, remember you are just going to look at the side chains, the side chains right here, here and this whole region here.2080

I am not going to pay attention to this carboxyl or amino group that is present on the backbone.2090

Right here, this is the simplest amino acid - I mentioned before - which is glycine, and glycine is non-polar. It just has a hydrogen.2098

This second amino acid is serine. Serine, you see, has a hydroxyl group, which is polar, so this is a polar amino acid.2109

Lysine is a little bit more complicated, and you will notice that it has an amino group.2120

When this is put in solution, this amino group is going to pick up a hydrogen ion and become NH₃⁺. Therefore, it is basic.2126

We have three amino acids, three different categories: non-polar hydrogen side chain, serine is polar with a hydroxyl group,2135

and finally lysine, which is a basic amino acid.2142

List four types of interactions that maintain the tertiary structure of a protein.2148

The first one is hydrogen bonding, and remember that this is hydrogen bonding between the side groups or the R-groups, not between the backbone.2154

Second type is hydrophobic interactions.2169

These occur as a result of amino acids with hydrophobic side chains being pushed towards the center of the2175

protein being excluded from the hydrogen bonding of water and the polar side chains of some of the other amino acids.2182

These are hydrophobic interactions.2188

A type of weak interaction between non-polar side chains is called Van der Waals interactions.2191

If there are some cysteine containing amino acids that are cysteine, they contain sulfur,2203

then, there may also be disulfide bridges that help to maintain this tertiary structure.2210

This was four, but a fifth one is ionic bonds between amino acids that are charged.2218

So, here is five. Any four of these would answer the question of the four types of interactions that maintain the tertiary structure of a protein.2231

That concludes this lecture on Educator.com.2239

Thanks for visiting.2242