WELCOME!

COURSE DESCRIPTION

Welcome to Molecular Cell Biology MB207! I hope that you find this course interesting and stimulating, and that you will be inspired to forge ahead in your studies of the biological world.

Molecular Cell Biology, as the name implies, is the study of the "Biology" of a "Cell" at the "Molecular" level. Basically, you will learn about what a CELL is, what it's made up of, how it goes about its everyday life and how it interacts with other cells and its environment. Molecular Cell Biology, a.k.a. MCB, is a fundamental subject in the field of Biotechnology, where a good grounding of everything to do with a living cell is important in understanding current biotechnological advances, tackling future problems and appreciating the beginnings of life itself.

The main objective of this course is to explain and illustrate various aspects of biochemistry and biology that are common to most organisms, and to provide a fundamental understanding of eukaryotic and prokaryotic cell structure and function. Lectures and discussions will explain and illustrate the following aspects of cellular biology:

• Cell structure and function,
• Cellular biochemistry and energy conservation mechanisms,
• Transcription and translation of the genetic code,
• The cell cycle, meiosis and mitosis, and cell division,
• Genetic aspects of development,
• Interaction of cells with each other and their environment,
• Applied molecular cell biology.

Introduction to the Cell - Overview & History

The Game of Life

The Game of Life is a serious one for all living organisms. An organism must be able to perform certain tasks to live, and survive competition from other individuals and species.

The Big Picture

While life forms are strikingly diverse on the outside, at the cellular level all life forms are strikingly similar.

History of the Cell 

"Cells are the unit of structure, function, and reproduction in living things." If this sounds confusing, here's a simpler definition: "Anything that's alive is made up of cells."

Every organism, whether it's an octopus, bird, snail or ant, is made of cells. Humans are made of literally billions of cells. We can't see them because cells are so small that they can only be seen under a microscope. Most organisms, like us, are made up of many different types of cells. Some carry oxygen in our blood, some produce sweat, and some allow us to feel whether it's hot or cold. 

Although most organisms (a living thing) are made of many different types of cells, all of which work together, some organisms are just one, single cell. Biologists call this type of organism unicellular. Unicellular organisms are very special in that they perform all of the functions necessary to live and yet are so tiny.

The study of cells is known as cytology. Cytology began in 1665, when Robert Hooke, an English scientist, first glimpsed into the microscopic world of cells by examining dead cork cells under a primitive microscope which he constructed. However, all Hooke was able to observe were the thick walls that surrounded each cell. The thought that cells might be the basis for life was not to come for nearly two centuries.

During the next 170 years, other scientists used microscopes to further advance their knowledge of cells. The most important discovery during that period came in 1838, when a German botanist named Matthias Schleiden suggested that all plant tissues are made of cells. Just one year later, zoologist Theodore Schwann made a similar proposal for animals. In 1858, Rudolf Virchow suggested that all cells come from preexisting cells. The ideas of these three scientists led to the creation of what is now called the cell theory. The three main aspects of the theory are: 

1. Aything that is living is composed of cells.
2. The chemical reactions that occur in an organism occur in cells.
3. All cells come from preexisting cells.

Remember the definition of a cell? The "unit of structure, function, and reproduction in living things." The cell theory says that all living things are composed of cells, so it makes sense that cells are called the unit of structure for an organism. An organism requires chemical reactions to function, and since the second part of the cell theory says that these reactions occur in cells, we can say that cells are the unit of function for the organism. The final component of the theory states that cells reproduce to form new cells. Since all living things reproduce and are also made of cells, the cells themselves must reproduce to form the new organism. That's why the definition also calls cells the unit of reproduction in living things.

Types of Cells

There are many different types of unicellular organisms, all of which fall into two general categories: prokaryotic organisms (also called bacteria) and eukaryotic organisms. In general, eukaryotic cells are more complex than prokaryotic organisms, because prokaryotes don't have membrane-bound organelles. Prokaryotes and eukaryotes also differ in the chemical composition of some of their structures as well as in the organization of their DNA. Below are the important differences between the two types of cells.

	Prokaryote	Eukaryote
cell membrane	yes	yes
nucleus	no membranes	surrounded by two membranes
endoplasmic reticulum	no	yes
Golgi bodies	no	yes
mitochondria	no	yes
vacuoles	no	yes
lysosomes	no	yes
ribosomes	yes	yes
chromosomes	circular without histones	linear with histones

In addition to this classification, organisms may also be classified according to their method of nutrition. Heterotrophs are organisms which obtain food from the environment, whereas autotrophs have a method of producing their own food. Also, aerobes are organisms which require oxygen to survive, whereas anaerobes do not need oxygen.

Introduction to the Cell - Chemistry of Life

Overview

Life has its basic requirements: chemical and physical requirements, energy requirements, and information storage and retrieval requirements. This topic touches on the chemical and physical properties that molecules, cells, and organisms have to obey. We will learn some of the chemical properties of the six most important elements of life – carbon, nitrogen, oxygen, hydrogen, phosphorous and sulfur. Then we will look at the major classes of macromolecules that are used to build cells - proteins, lipids, carbohydrates and nucleic acids. 

Chemical Interactions

All living things are made up of chemical compounds. Therefore, chemical interactions are a crucial component of life. The majority of living tissue is made up of only a few elements. In addition, there are only five main types of chemical interactions that are found in chemical compounds. 
  

Organic molecules are molecules that contain carbon and hydrogen. All living things contain these organic molecules: carbohydrates, lipids, proteins, and nucleic acids. These molecules are often called macromolecules because they may be very large, containing thousands of carbon and hydrogen atoms and because they are typically composed of many smaller molecules bonded together. 

Carbon

Carbon has four electrons in its outer shell.

Hydrogen has one electron and one proton.

Carbon can bond by covalent bonds with as many as 4 other atoms.

The diagram above shows a molecule of methane. Lines can be used to represent bonds in the shorthand formula seen in the upper right side of the diagram. Carbon can also form double covalent (shares 2 pairs of electrons) or triple covalent bonds (shares 3 pairs).

Carbon can form 4 covalent bonds because it has 4 electrons in its outer shell. It can form the following number of bonds. Notice that in each case below, there is a total of four bonds.

• 4 single bonds
• two double bonds
• one double bond and two single bonds
• one triple and one single bond

Long chains of carbon atoms are common. The chains may be branched or form  rings.

Hydrophilic and Hydrophobic

Polar and ionic molecules have positive and negative charges and are therefore attracted to water molecules because water molecules are also polar. They are said to be hydrophilic because they interact with (dissolve in) water by forming hydrogen bonds.

Nonpolar molecules are hydrophobic (means "water fearing"). They do not dissolve in water.

	Nonpolar molecules are hydrophobic.
	Polar and ionic molecules are hydrophilic.

Portions of large molecules may be hydrophobic and other portions of the same molecule may be hydrophilic.

Functional Groups

Organic molecules may have functional groups attached. A functional group is a group of atoms of a particular arrangement that gives the entire molecule certain characteristics. Functional groups are named according to the composition of the group. For example, COOH is a carboxyl group.

Organic chemists use the letter "R" to indicate an organic molecule. For example, the diagram below can represent a carboxylic acid. The "R" can be any organic molecule.

Some functional groups are polar and others can ionize. For example, if the hydrogen ion is removed from the COOH group, the oxygen will retain both of the electrons it shared with the hydrogen and will have a negative charge. The hydrogen that is removed leaves behind its electron and is now a hydrogen ion (proton).



If polar or ionizing functional groups are attached to hydrophobic molecules, the molecule may become hydrophilic due to the functional group. Some ionizing functional groups are: -COOH, -OH, -CO, and -NH₂.

Some important functional groups are shown below.

Name	Structure
	Non-ionized	Ionized
Hydroxyl
Carboxyl
Amino
Phosphate
Sulfhydryl
Aldehyde
Ketone

Macromolecules and Monomers

Many of the common large biological molecules (macromolecules) are synthesized from simpler building blocks (monomers). Each of the types of molecules listed in the table are discussed below.

Example of a Macromolecule	Monomer
polysaccharide (complex carbohydrate)	monosaccharide (simple sugar)
fat (a lipid)	glycerol, fatty acid
protein	amino acid
nucleic acid	nucleotide

Condensation

In order to bond the two molecules shown below together, you must first remove a hydrogen from each one. This is necessary because carbon has a maximum of 4 bonds and hydrogen can have only one.

In biological systems, macromolecules are often formed by removing H from one atom and OH from the other (see the diagram below). The H and the OH combine to form water. Small molecules (monomers) are therefore joined to build macromolecules by the removal of water. The diagram below shows that sucrose (a sugar) can be produced by a condensation reaction of glucose and fructose.

Sucrose:

This is called a condensation or dehydration reaction.
Energy is required to form the bond.

Hydrolysis

This is a type of reaction in which a macromolecule is broken down into smaller molecules.
It is the reverse of condensation (above).

 Proteins

Importance of proteins

Some important functions of proteins are listed below.

enzymes (chemical reactions)

hormones

storage (egg whites of birds, reptiles; seeds)

transport (hemoglobin)

contractile (muscle)

protective (antibodies)

membrane proteins (receptors, membrane transport, antigens)

structural

toxins (botulism, diphtheria)

Enzymes

Enzymes are proteins that speed up the rate of chemical reactions.

Example:

The presence of an enzyme in the chemical reaction diagrammed below causes hypothetical chemicals A and B to react, producing C.

                                                      

Proteins are able to function as enzymes due to their shape. For example, enzyme molecules are shaped like the reactants, allowing the reactants to bind closely with the enzyme. The diagrams below show that the enzyme matches the shape of the substrate molecules. The enzyme is therefore able to hold the substrate molecules in the correct orientation needed for the chemical reaction to proceed. The enzyme does not participate in the reaction and is not changed by the reaction.

Amino Acids

Amino acids are the building blocks of proteins.

Twenty of the amino acids are used to make protein. Each has a carboxyl group (COOH) and an amino group (NH₂).

Each amino acid is different and therefore has its own unique properties.

Some amino acids are hydrophobic, others hydrophilic. The carboxyl or amino group may ionize (forming NH₃⁺ or COO^-). The "R" group of some amino acids is nonpolar and the "R" group of some others is polar or it ionizes.

Amino acids are joined together by a peptide bond. It is formed as a result of a condensation reaction between the amino group of one amino acid and the carboxyl group of another.

Polypeptides

Two or more amino acids bonded together are called a peptide. A chain of many amino acids is referred to as a polypeptide.  The complete product, either one or more chains of amino acids, is called a protein.
There is unequal sharing of electrons in a peptide bond. The O and the N are negative and the H is positive.

Levels of structure

The large number of charged atoms in a polypeptide chain facilitates hydrogen bonding within the molecule, causing it to fold into a specific 3-dimensional shape.
The 3-dimensional shape is important in the activity of a protein.

Primary Structure

Primary structure refers to the sequence of amino acids found in a protein. The following is the primary structure of one of the polypeptide chains of hemoglobin.

val his leu thr pro glu glu lys ser ala val thr ala leu tyr gly lys val asn val asp glu val gly gly glu ala leu gly arg leu leu val val tyr pro try thr gln arg phe phe glu ser phe gly asp leu ser thr pro asp ala val met gly asn pro lys val lys ala his gly lys lys val leu gly ala phe ser asp gly leu ala his leu asp asp leu lys gly thr phe ala thr leu ser gln leu his cys asp lys leu his val asp pro glu asn phe arg leu leu gly asn val leu val cys val leu ala his his phe gly lys glu phe thr pro pro val gln ala ala tyr gln lys val val ala gly val ala asp ala leu ala his lys tyr his

Secondary structure

The oxygen or nitrogen atoms of the peptide bond are capable of hydrogen- bonding with hydrogen atoms elsewhere on the molecule. This bonding produces two common kinds of shapes seen in protein molecules, coils (called alpha helices) and beta pleated sheets. The alpha helices and beta pleated sheets are referred to as a proteins secondary structure.

Tertiary structure

Tertiary structure refers to the overall 3-dimensional shape of the polypeptide chain. 

Hydrophobic interactions with water molecules are important in creating and stabilizing the structure of proteins.  Hydrophobic (nonpolar) amino acids aggregate to produce areas of the protein that are out of contact with water molecules.

Hydrophilic (polar and ionized) amino acids form hydrogen bonds with water molecules due to the polar nature of the water molecule.

Hydrogen bonds and ionic bonds form between R groups to help shape the polypeptide chain.

Disulfide bonds are covalent bonds between sulfur atoms in the R groups of two different amino acids.  These bonds are very important in maintaining the tertiary structure of some proteins.

The shape of a protein is typically described as being globular or fibrous.  Globular proteins contain both coils and sheets.

Quaternary structure

Some proteins contain two or more polypeptide chains that associate to form a single protein.  These proteins have quaternary structure.   For example, hemoglobin contains four polypeptide chains.

Denaturation

Denaturation occurs when the normal bonding patterns are disturbed causing the shape of the protein to change.  This can be caused by changes in temperature, pH, or salt concentration. For example, acid causes milk to curdle and heat (cooking) causes egg whites to coagulate because the proteins within them denature.
 If the protein is not severely denatured, it may regain its normal structure.

Nucleic Acids

DNA

DNA (deoxyribonucleic acid) is the genetic material. An important function of DNA is top store information regarding the sequence of amino acids in each of the body’s proteins. This "list" of amino acid sequences is needed when proteins are synthesized. Before protein can be synthesized, the instructions in DNA must first be copied to another type of nucleic acid called messenger RNA.

Structure of DNA

Nucleic acids are composed of units called nucleotides, which are linked together to form a larger molecule. Each nucleotide contains a base, a sugar, and a phosphate group. The sugar is deoxyribose (DNA) or ribose (RNA). The bases of DNA are adenine, guanine, cytosine, and thymine. Notice that the carbon atoms in one of the nucleotides diagrammed below have been numbered.

The diagram below shows how nucleotides are joined together to form a "chain" of nucleotides.

DNA is composed of two strands in which the bases of one strand are hydrogen-bonded to the bases of the other. The sugar-phosphate groups form the outer part of the molecule while the bases are oriented to the center.

The strands are twisted forming a configuration that is often referred to as a double helix. The photograph below is of a model of DNA.

Complimentary base pairing

The adenine of one strand is always hydrogen-bonded to a thymine on the other. Similarly, Guanine is always paired with Cytosine.

A-T

G-C

Antiparallel

The end of a single strand that has the phosphate group is called the 5’ end. The other end is the 3’ end.

The two strands of a DNA molecule run in opposite directions. Note the 5’ and 3’ ends of each strand in the diagram.

RNA

RNA (ribonucleic acid) is similar to DNA and is involved in the synthesis of polypeptides and proteins as discussed above. The table below lists differences between DNA and RNA.

	DNA	RNA
# Strands	2	1 (see diagram below)
Sugar	deoxyribose	ribose
Bases	A, T, G, C	A, U, G, C

RNA is single-stranded as shown below.

Codons

One strand of DNA (the anti-sense strand) is used as a template to produce a single strand of mRNA. The bases in the mRNA strand are opposite (complimentary) to the bases in the DNA template strand; it resembles the sense strand of DNA except that the base thymine is replaced by uracil. The mRNA contains three-letter (three-base) codes used to determine the sequence of amino acids in the polypeptide that it codes for. For example, in the diagram below, GUG is the code for valine. The sequence of codes in DNA therefore determines the sequence of amino acids in the protein.

Each three-letter code in mRNA is a codon. It is the code for one amino acid.

ATP

ATP (adenosine triphosphate) is a nucleotide that is used in energetic reactions for temporary energy storage.

Energy is stored in the phosphate bonds of ATP. When ATP breaks down to form ADP and P_i, energy is released. Normally, cells use the energy stored in ATP by breaking one of the phosphate bonds, producing ADP. Energy is required to convert ADP + P_i back to ATP.

ATP is continually produced and consumed as illustrated below.

Carbohydrates

The general formula for carbohydrates is (CH₂O)_n.

Monosaccharides

Monosaccharides are simple sugars, having 3 to 7 carbon atoms. They can be bonded together to form polysaccharides.
The names of most sugars end with the letters ose.
Example: Glucose, fructose, and galactose are monosaccharides; their structural formula is C₆H₁₂O₆.
Glucose and other kinds of sugars may be linear molecules as shown below but in aqueous solution they become a ring form.

There are two isomers of the ring form of glucose. They differ in the location of the OH group on the number 1 carbon atom (in red below).

The number 1 carbon atom (numbered in red above) of the linear form of glucose is attached to the oxygen on the number 5 carbon atom.

Simple sugars store energy for cells. Details concerning energy storage and release by glucose are in the chapter on cellular respiration.

Cells also use simple sugars to construct other kinds of organic molecules.

Disaccharides

Disaccharides are composed of 2 monosaccharides joined together by a condensation reaction.

Examples:

Sucrose (table sugar) is composed of glucose and fructose.

Like glucose, sucrose stores energy. Plants synthesize sucrose to transport to nonphotosynthetic parts of the plant.

Lactose is found in milk. It is formed when glucose bonds to galactose.
The digestion of complex carbohydrates (polysaccharides) typically involves hydrolysis reactions in which the molecules are broken down to maltose, a disaccharide. Maltose is then further broken down to produce two glucose molecules.

Polysaccharides

Monosaccharides may be bonded together to form long chains called polysaccharides.

Starch and Glycogen

Starch and glycogen are polysaccharides that function to store energy. They are composed of glucose monomers bonded together producing long chains.

Animals store extra carbohydrates as glycogen in the liver and muscles. Between meals, the liver breaks down glycogen to glucose in order to keep the concentration of glucoses in the blood stable. After meals, as glucose levels in the blood rise, it is removed from and stored as glycogen. Plants produce starch to store carbohydrates.

Amylopectin is a form of starch that is very similar to glycogen. It is branched but glycogen has more branches. Amylose is a form of starch that is unbranched.
Below: Glycogen or Starch

Cellulose and Chitin

Cellulose and Chitin are polysaccharides that function to support and protect the organism. The cell walls of plants are composed of cellulose. The cell walls of fungi and the exoskeleton of arthropods are composed of chitin.

Cellulose is composed of beta-glucose monomers; starch and glycogen are composed of alpha-glucose. The bond orientation between the glucose subunits of starch and glycogen allows the polymers to form compact spirals. The monomers of cellulose and chitin are bonded together in such a way that the molecule is straight and unbranched. The molecule remains straight because every other glucose is twisted to an upside-down position compared to the two monomers on each side. Cellulose fibers are composed of long parallel chains of these molecules. The chains are attached to each other by hydrogen bonds between the hydroxyl groups of adjacent molecules.

Below: Cellulose

The glucose monomers of chitin (N-acetyl glucosamine) have a side chain containing nitrogen.

Cotton and wood are composed mostly of cellulose.  They are the remains of plant cell walls.

Digestibility of Cellulose and Chitin

Humans and most animals do not have the necessary enzymes needed to break the linkages of cellulose or chitin. Animals that can digest cellulose often have microorganisms in their gut that digest it for them. Fiber is cellulose, an important component of the human diet.

Lipids

Lipids are compounds that are insoluble in water but soluble in nonpolar solvents.
Some lipids function in long-term energy storage. One gram of fat stores more than twice as much energy as one gram of carbohydrate. Lipids are also an important component of cell membranes.

Fats and Oils (Triglycerides)

Fats and oils are composed of fatty acids and glycerol.

Fatty acids have a long hydrocarbon (carbon and hydrogen) chain with a carboxyl (acid) group. The chains usually contain 16 to 18 carbons. Glycerol contains 3 carbons and 3 hydroxyl groups. It reacts with 3 fatty acids to form a triglyceride or fat molecule.

Fats are nonpolar and therefore they do not dissolve in water.

Saturated and Unsaturated Fat

Saturated fatty acids have no double bonds between carbons. Unsaturated fatty acids have at least one double bond. Each double bonds produces a "bend" in the molecule.

Double bonds produce a bend in the fatty acid molecule (see diagram above). Molecules with many of these bends cannot be packed as closely together as straight molecules, so these fats are less dense. As a result, triglycerides composed of unsaturated fatty acids melt at lower temperatures than those with saturated fatty acids. For example, butter contains more saturated fat than corn oil, and is a solid at room temperature while corn oil is a liquid.

Phospholipids

Phospholipids have a structure like a triglyceride (see diagram above), but contain a phosphate group in place of the third fatty acid. The phosphate group is polar and therefore capable of interacting with water molecules.

Phospholipids spontaneously form a bilayer in a watery environment. They arrange themselves so that the polar heads are oriented toward the water and the fatty acid tails are oriented toward the inside of the bilayer (see the diagram below). In general, nonpolar molecules do not interact with polar molecules. This can be seen when oil (nonpolar) is mixed with water (polar). Polar molecules interact with other polar molecules and ions. For example table salt (ionic) dissolves in water (polar). The bilayer arrangement shown below enables the nonpolar fatty acid tails to remain together, avoiding the water. The polar phosphate groups are oriented toward the water.

Membranes that surround cells and surround many of the structures within cells are primarily phospholipid bilayers.

Steroids

Steroids have a backbone of 4 carbon rings.

Cholesterol (see diagram above) is the precursor of several other steroids, including several hormones. It is also an important component of cell membranes.
Saturated fats and cholesterol in the diet can lead to deposits of fatty materials on the linings of the blood vessels.

Waxes

Waxes are composed of a long-chain fatty acid bonded to a long-chain alcohol
They form protective coverings for plants and animals (plant surface, animal ears).

Other Kinds of Molecules

Simple proteins contain only amino acids. Conjugated proteins contain other kinds of molecules. For example, glycoproteins contain carbohydrates, nucleoproteins contain nucleic acids, and lipoproteins contain lipids.

Water & pH

Organisms are made up of 40-50% water to >90% water. The majority of the important chemical reactions of life occur in water. This indicates that water is essential for life as we know it. Ultimately, water’s importance can be attributed to its chemical structure. Water’s chemical structure gives it some important properties that help make life possible.