The cell as a basic unit of a living organism, each carrying out many different functions.

Introduction

When we look at cells we now also look at subcellular organization and components. We have to understand what the macromolecules in cells are, where they are found and how they work.

Here is a very brief review of biochemistry and how this affects cells.

The following material is based and borrowed from:

Biochemistry online: An approach based on chemical logic – this is the rectangle diagram of the cell

http://employees.csbsju.edu/hjakubowski/classes/ch331/bcintro/default.html

and Inside the Cell – these include the other diagrams except where stated. http://publications.nigms.nih.gov/insidethecell/pdf/inside_the_cell.pdf

Three important ideas from chemistry are:

· Molecules have structure, charge, and electron distribution which will cause the function/activity of the molecule;

· Binding reactions are what start all biological events; and

· Chemical ideas can be applied to the behavior of macromolecules.

The General Cell

This leads us to some questions. First we will think of a general cell.

http://en.wikipedia.org/wiki/Cell_(biology)#/media/File:Animal_cell_structure_en.svg artist is LadyofHats (Mariana Ruiz)

 

ACTUAL SIZE (AVERAGE)

SIZE WHEN MAGNIFIED 3 MILLION TIMES (meters)

Cell diameter

30 micrometers*

90

Nucleus diameter

5 micrometers

15

Mitochondrion length

Typically 1–2 micrometers, but can be up to 7 micrometers long

3 - 7

Lysosome diameter

50–3,000 nanometers

0.15 - 9

Ribosome diameter

20–30 nanometers

0.06 - 0.09

Microtubule width

25 nanometers

0.75

Intermediate filament width

10 nanometers

0.03

Actin filament width

5–9 nanometers

0.015 - 0.027

Cell membrane

6 or more nanometers

0.018

We can now redraw this cell by thinking about the different functions of the cell.

http://employees.csbsju.edu/hjakubowski/classes/ch331/bcintro/default.html

This diagram shows grouping of functions

· Storage and retrieval of information

· Enclosing structures and separating the cell from the environment.

· Making, folding and transporting proteins

· Making membrane receptors and channels, and letting things through the membrane.

· Differentiation and gene control

· Regulation and linking of biochemical reactions

· Catalysis of biochemical reactions

· Sensing and responding to the environment and sending signals

Storage and retrieval of information

The genetic information

· stored in DNA

· transcribed into an RNA molecule.

· information is then translated into a protein.

Genetic material - DNA

Genes, each with a set of helper molecules

Nucleus is surrounded by two membranes, together known as the nuclear envelope.

The nuclear envelope has many octagonal pores.

Nuclear pores allow chemical messages to exit and enter the nucleus.

Each cell - about 10 billion protein molecules of about 10,000 different types.

Proteins are responsible for a wide range of tasks, eg

· carrying oxygen (hemoglobin),

· digesting food (enzymes like amylase, pepsin, and lactase),

· fighting invading microorganisms (antibodies), and s

· speeding up chemical reactions inside your body (enzymes).

Many factors—such as diet, activity level, age, sickness and environment—can affect when and how the cell will use genes.

transcription

· reading the genetic code contained in DNA.

· Inside the cell nucleus, DNA is packaged in chromosomes,

· RNA polymerases.

· a dozen different small proteins,

· molecular machines first pull apart the two strands of DNA,

· then transcribe the DNA into RNA.

X-ray crystallography helps show how transcription occurs. Eg

· Kornberg made a detailed, three- dimensional image of RNA polymerase.

· the RNA polymerase enzyme uses

· a pair of jaws to grip DNA,

· a clamp to hold it in place,

· a pore through which RNA components enter, and

· grooves for the completed RNA strand to thread out of the enzyme.

Helper molecules

· cut and join together pieces of RNA

· make a few chemical modifications to give the finished products - correctly sized and processed strands of messenger RNA (mRNA).

Completed mRNA molecules carry genetic messages to the cytoplasm, where they are used as instructions to make proteins.

Specialized proteins and small RNA molecules escort the mRNA out of the nucleus through pores in the nuclear envelope.

Chemical reactions that use ATP drives this export process.

translation

· in the cell’s cytoplasm,

· mRNA molecule serves as a template to make a single type of protein.

· a single mRNA message can be used over and over again to create thousands of identical proteins.

· process is carried out by ribosomes,

· move along the mRNA

· read mRNA bases in groups of three (codons),

· each codon codes for protein building blocks called amino acids.

· ribosomes read the mRNA codons in sequence and join the corresponding amino acids in the proper order.

Ribosomes

- molecular machines made up of more than 70 proteins and 4 strands of RNA.

- made mostly of RNA

- assemble all the cell’s proteins.

Newly made protein chains come out of ribosomes, and thread directly into the ER (Endoplasmic reticulum).

enzymes add special sugars to the protein.

In 1999 scientists got the first structural picture of an entire ribosome.

This image shows a bacterial ribosome making a protein.

Knowledge of ribosomal structures could lead to improved antibiotic medicines.

· All cellular organisms, including bacteria, have ribosomes.

· the shapes of ribosomes differ in several ways between humans and bacteria.

· several antibiotic medicines work by inhibiting the ribosomes of bacteria.

· many microorganisms have developed resistance to these medicines.

· need new antibiotics to replace those that don’t work.

Imaging techniques like X-ray crystallography have produced molecular pictures of antibiotics grabbing onto a bacterial ribosome.

These 3D images gives new ideas about how to design molecules that grip bacterial ribosomes even more strongly.

This may result in new and more effective antibiotic drugs.

Therapies that knock out bacterial ribosomes (kills the bacteria) should work without affecting the human hosts.

Ribosomes get the amino acids from transfer RNAs (tRNAs)

· bring amino acids from the cytosol to the ribosome.

· one end of the L-shaped tRNA matches up with a codon while the other end carries the appropriate amino acid.

A finished amino acid chain can range in length from a few dozen to several thousand amino acids.

Translation uses lots of energy, but it happens very fast.

In bacteria, for example, ribosomes can join together 20 amino acids in 1 second.

Some three-unit sequences in the mRNA message can immediately stop protein production. Reading one of these mRNA stop signs indicates to the ribosome that the new protein has all the amino acids it needs, and translation ends.

Proteins made by ribosomes on the rough ER.

· enzymes add specialized chains of sugar molecules (carbohydrates) to proteins in a process called glycosylation.

· the proteins go to the Golgi, where the sugar groups may be cut or changed in to create the final protein.

· carbohydrates are not based on a genetic template.

· they are more difficult to study because we can’t easily find the sequence or arrangement of their components.

· beginning to learn about the important roles carbohydrates play in many life processes.

Eg 1, a fertilized egg needs special carbohydrates on its outer surface to implant into a woman’s uterus.

Eg 2, sticky sugar molecules slow down immune cells, so they can stop to help fight infection.

Eg 3, sugars attached to lipids on the surface of red blood cells define a person’s blood type (A, B, AB, or O).

Eg 4, carbohydrates help proteins fold up into their proper shape and say where proteins go and which other molecules they can interact with.

Enclosing structures and separating the cell from the environment.

Lipids join thermodynamically spontaneously to form structures like biological membranes.

Without membranes cells and life could not exist.

A summary of lipids is at

http://employees.csbsju.edu/hjakubowski/classes/ch250/CelltutorialCHEM250_Lipids.pptx The site is written and maintained by Henry V. Jakubowski, Ph.D., College of Saint Benedict / Saint John's University.  and available for educational use.

Membrane’s location and role in the body

- lipids can make up anywhere from 20 to 80 percent of the membrane,

- the remainder is proteins.

Cholesterol is a type of lipid that helps stiffen the membrane.

About half of all human proteins include chains of sugar molecules that are critical for the proteins to function properly.

Making, folding and transporting proteins

Proteins fold to form structures with a unique 3D shape.

These 3D structures give a specific function to proteins.

Proteins are synthesized in the cytoplasm and transported to where they are needed

The Golgi complex, also called the Golgi apparatus or the Golgi.

· receives newly made proteins and lipids from the ER,

· finishes the production

· add a molecular address

· sends them to their final destinations.

Cytoskeleton gives cells

· shape,

· strength,

· the ability to move

· constantly shrink and grow to meet the needs of the cell

Three fibres of the cytoskeleton –

· microtubules,

· intermediate filaments, and

· actin filaments.

Each type of fiber looks, feels, and functions differently.

Microtubules

· Made of tubulin

· separating duplicate chromosomes when cells copy themselves

· act as structures on which molecules and materials move.

· hold the ER and Golgi in stacks

· form the main component of flagella and cilia.

Intermediate filaments - vary greatly according to their location and function in the body.

some form tough coverings,

Others are in nerve cells, muscle cells, the heart, and internal organs.

In each of these tissues, the filaments are made of different proteins. So if doctors analyze intermediate filaments in tumors, they can determine the origin of some kinds of cancer.

Actin filaments - two chains of the protein actin twisted together.

· can gather together into bundles, weblike networks, or even three-dimensional gels.

· shorten or lengthen to allow cells to move and change shape.

· Together with myosin, actin filaments make possible the muscle contractions.

To reach its destination, a newly created protein must be moved through the cytosol, moving past obstacles, such as organelles, cytoskeletal fibers, and many molecules.

Well-organized systems bring proteins to the places where they are needed.

Vesicles

· Membranes are an important obstacle.

· The cell’s cytosol, the insides of organelles, and many proteins are water-soluble.

· But the insides of membranes are fat-soluble (oily).

· Oil and water don’t mix.

· Water-loving proteins are wrapped in vesicles.

· They can cross the fatty membranes surrounding lysosomes, the ER, or the Golgi.

· Vesicles are protective membrane bubbles.

Eg. proteins from the ER to the Golgi.

· A small portion of the ER membrane pinches off, enveloping proteins in a vesicle that has a special molecular coat.

· This vesicle then travels to the Golgi.

· Docking sites on the Golgi permit vesicles to latch onto and fuse with its outer membrane to release their contents inside.

· The same process takes proteins in vesicles from the Golgi to lysosomes or to the cell’s surface.

Cells also use vesicles to carry nutrients and other materials into the cell in a process called endocytosis.

White blood cells use endocytosis to fight infection.

· They engulf bacteria in large vesicles.

· The vesicles then fuse with lysosomes, which break down the bacteria into molecular pieces the cell can use.

Endocytosis occurs continuously, and cells use their entire membrane every 30 minutes.

Exocytosis, counterbalances endocytosis.

Cells use this process to put wastes out of the cell and to replace membrane.

Secretory vesicles

· organize cell activities

· communicate with cell environment.

· direct proteins and other molecules to their proper destinations.

Vesicles are very important for cells.

· many processes, such as

· the secretion of insulin to control blood sugar,

· nerve cell communication, and

· the proper development of organs.

Genetically altered yeast cells now pump out many important products, including approximately one-quarter of the world’s insulin supply and a key ingredient in hepatitis B vaccines.

Molecular Motors

· Vesicles and many other materials inside the cell, including some organelles, often are carried by small molecular motors along tracks formed by the cytoskeleton.

· Motors are used in the cell to get many things done —

· copying DNA (and fixing it when a mistake is made),

· making ATP and proteins, and

· putting molecules in the correct places during development to make sure the body is assembled correctly.

Every motor examined uses the same two ingredients:

· an energy source (usually ATP) and

· chemical reactions.

Making membrane receptors and channels, and letting things through the membrane.

Proteins form membrane receptors and channels

Proteins allow passage of hydrophilic molecules into the cell.

Cells have a different way to transport smaller molecules, like water and charged particles (ions), across membranes.

These molecules travel through hollow or gated proteins that form channels through membranes.

Channel proteins are a family of proteins that function within the cell’s surface membrane.

They transport ions like sodium and potassium that are important to many biological processes, eg

· the beating of the heart,

· nerve impulses,

· digestion, and

· insulin release.

Unfortunately, channel proteins are difficult to study because they cannot easily be isolated from the membrane in either their natural or active states.

Differentiation and gene control

Proteins catalyze and regulate how specific proteins are made.

A cell knows what kind of cell it is to be.

A cell knows what kind of proteins to make.

How can cells be so similar, yet so different?

· still don’t fully understand how developing cells turn into all the different types

· but this process, called differentiation, is governed by genes.

· depending on where in the body it is, a given gene can be turned off, weakly on, or strongly on.

· For example, the gene for globin, which is part of hemoglobin, is strongly on in cells that will mature into red blood cells and off in every other cell type.

Cells control the expression, of genes by controlling RNA polymerase.

For genes that are strongly on, cells use special molecular tags to bring in RNA polymerase and to ensure that the machine works to transcribe those genes.

For genes that are off, cells use different tags to repel RNA polymerase.

Very special cells

embryonic stem cells

· gene expression is very wide

· has potential to become any kind of cell in the body.

· cease to exist a few days after conception.

Regulation and linking of biochemical reactions

Enzymatic reactions be regulated so the cell can biosynthesize and get energy.

Reactions are brought together in pathways.

Whole pathways are regulated.

Eg. Through a series of chemical reactions, mitochondria transfer energy from glucose into ATP.

All that’s left are carbon dioxide and water, which are discarded as wastes.

This process is extremely efficient.

Cells convert nearly 50 percent of the energy stored in glucose into ATP.

There are many reactions in the cell and many are linked to form biochemical pathways.

The reactions are controlled in many ways.

The cell is a very complex system.

Scientists interested in metabolomics study how metabolism (the body’s breakdown of certain molecules and the synthesis of others) is governed by thousands of enzymes and signaling networks in an organism.

-omics tagged on to the end of a word means a systematic survey of an entire class of molecules.

Catalysis of biochemical reactions

Enzymes catalyze biochemical reactions.

We can find out these workings.

Sensing and responding to the environment and sending signals

Cells sense environmental signals and respond the correct way.

Cells send out chemical signals.

Here is a diagram which shows the different proteins of cells (different genes) grouped by function.

Write down these groups from the biggest to the smallest in the following table.

Write down the functions of each group.

Group

Functions of Group

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