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INTRODUCTORY BIOLOGY INTRODUCTORY BIOLOGY LIFE OF A CELL LESSON 3 LESSON 3 Wild Rose College of Natural Healing Martha J. McCallum ©2009 1 Lesson 3 Lesson 3 The Life of a Cell The Life of a Cell (Part one) (Part one) A cell is the basic, living, structural and functional unit of the body. It is where activities essential to life occur, and where disease processes originate. CELL THEORY CELL THEORY One of the foundations of modern biology is cell theory. The cell theory holds that all organisms are composed of cells and all cells come from pre-existing cells. Obviously, the very first cells have to be an exception! After reading this chapter you will have a new understanding of how closely we are related to worms. The very first cells are believed to have formed from organic molecules in the Earth’s early environment, 3.7 billion years ago. It is thought that these first cells resembled modern bacteria, and dominated the Earth’s oceans for over 2 billion years. Prokary Prokary otic and eukaryotic cells otic and eukaryotic cells The earliest cells, and modern bacteria, are known as prokaryotes. They have a single circular strand of DNA but otherwise show little differentiation within the cell. They belong to the kingdom of organisms known as the Monera, which includes modern-day bacteria.

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Lesson 3Lesson 3 The Life of a CellThe Life of a Cell (Part one)(Part one)

A cell is the basic, living, structural and functional unit of the body. It is where activities essential to life occur, and where disease processes originate.

CELL THEORYCELL THEORY One of the foundations of modern biology is cell theory. The cell theory holds that all organisms are composed of cells and all cells come from pre-existing cells. Obviously, the very first cells have to be an exception! After reading this chapter you will have a new understanding of how closely we are related to worms. The very first cells are believed to have formed from organic molecules in the Earth’s early environment, 3.7 billion years ago. It is thought that these first cells resembled modern bacteria, and dominated the Earth’s oceans for over 2 billion years.

ProkaryProkaryotic and eukaryotic cellsotic and eukaryotic cells The earliest cells, and modern bacteria, are known as prokaryotes. They have a single circular strand of DNA but otherwise show little differentiation within the cell. They belong to the kingdom of organisms known as the Monera, which includes modern-day bacteria.

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More complex cells evolved from the prokaryotes about 2.5 billion years later. These eukaryotes contain DNA within a cell nucleus. The earliest eukaryotes lived as single-celled organisms. These organisms and their modern descendents such as the aquatic amoebae and paramecia belong to the kingdom Protista.

During evolution, protists gave rise to three new kingdoms: plants, fungi and animals. All five kingdoms exist today. The evolution of these three new kingdoms was possible due to the development of multicellular organisms, and the development of cells that perform specialized tasks. These two developments led to an increase in the overall complexity of life on earth, many new developments such as our complex sensory and motor systems, the capabilities of species to adapt to many environments and the diversity of species on earth.

Growing complexity required mechanisms to maintain balance in the internal environment – homeostatic control. Body systems such as the nervous system and endocrine system evolved to control a wide variety of functions.

The number of cells in the human body is so huge that no biologist can count them. They toss around numbers like 60 trillion or 100 million million without an accurate way to estimate the answer. The following description of plant and animal cells combines the components of all of our different cells into one “typical” cell that does not really exist, since our cells differentiate to perform specialized functions.

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Similarities and differences between Similarities and differences between plant and animal cellsplant and animal cells

Given the obvious differences between animals and plants, there are a surprising number of similar features in plant and animal cells, no doubt because they evolved from the same stock. It should be noted that the cells we describe here are a generalization of all the structures found in plant or animal cells. Actual cells within organisms are more specialized and do not contain all the structures we will look at.

Both plant and animal cells are highly compartmentalized, with the two main compartments being within the cell nucleus and outside it, in the cell cytoplasm. The nucleus is surrounded by a double membrane, and contains the genetic information that controls the structure and function of the cell.

The cytoplasm of plant and animal cells contains numerous organelles in a solution of water, proteins, nutrients, ions, vitamins, dissolved gasses, and waste products. You can think of

CellCell Differentiation:Differentiation: All the cells in our body had the potential at one time to become any type of cell – to be a liver cell that detoxifies alcohol, or a sensory neuron that tells us to jump back when we touch a flame, or specialized rod or cone in the retina of our eye. Long before we are born, as our cells first divide, they start to grow into different types of tissue. Our sex is not determined until an embryo is 6 weeks old, when we become male if we have a single gene located on the Y chromosome that initiates testosterone production. If we lack this single gene, we become female! In each of our cells we have the same DNA, but only some parts are active in each cell. It is the regulatory and control genes in each cell that turn on some cell functions and turn off most of the others. This way, a cell in our pancreas can focus on producing insulin and does not have the ability to sense pain or store fat. All our lives, stem cells in our bone marrow continue to grow and differentiate into different types of blood cells, depending on the presence of different hormones and growth factors, which in turn were produced under genetic control.

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it as a pool from which the cell organelles draw the nutrients they need for metabolism, and a dumping ground for their wastes.

Organelles are structures that carry out specific functions. There are some organelles that plants and animals do not share, since they have evolved in such different ways. Animals are mobile and plants synthesize their own food. Most plants contain a rigid cell wall that helps give them their shape. They also contain chloroplasts, organelles that capture light and produce food through the process of photosynthesis. Most plant cells lack centrioles, which are small tubules that play a role in cell division in animal cells and primitive plant cells.

Cells maintain their shape from their cytoskeleton, a network of protein tubules and filaments found in the cytoplasm. This organelle is also the site of some metabolic pathways, since it offers a site for enzymes to bind in the order in which certain metabolic processes need to occur.

THE PLASMA MEMBRANETHE PLASMA MEMBRANE The plasma membrane, or cell membrane, is a thin barrier

between the cell contents and the extracellular environment. It is 10 nanometres, or !,500,000 of an inch thick. The plasma membrane controls all substances that enter and leave the cell, by diffusion or active pumping. It surrounds every cell of all plants and animals – a very important characteristic that we share with mosquitoes to dandelions! The membrane structure is described by the fluid mosaic model as a mosaic of proteins floating like icebergs in a sea of lipids. The proteins form pores through which some materials can

pass, and the lipids form a double layer known as the lipid bilayer. By weight, there are approximately equal amounts of proteins and lipids in the cell membrane. However, since the lipid molecules are a lot smaller, there are about 50 lipid molecules for each protein molecule (Figure 3-1).

Plasma Membrane lipids Plasma Membrane lipids

Figure 3.1 Plasma membrane

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Membrane lipids are comprised of about 75% phospholipids, 20% cholesterol, and 5% glycolipids. These lipids are all manufactured in the liver. Phospholipids line up in two parallel layers, forming a phospholipid bilayer. They do this because they are amphipathic, having both polar and non-polar regions. The phosphate-containing “heads” are polar and mix well with water, or cytoplasm and extra-cellular fluids. The fatty acid tails are non-polar and hydrophobic. Thus the phospholipids organize themselves so that the fatty acid tails are sandwiched together in between the double layer of polar heads.

Glycolipids are lipids with one or more sugar molecules attached. They are also amphipathic, and are found only in the outer layer of the phospholipid bilayer. Their functions are not all well known, but it is known that they are the target of some bacterial toxins. They are also thought to be important for adhesion among cells and tissues, for cell-to-cell recognition and communication, and in the regulation of cell growth.

Cholesterol, a lipid, is located throughout the phospholipid bilayer of animal cell membranes, and is not found in plant cells. Its stiff rings strengthen the membrane but decrease its flexibility. They are not required in plant cells, since the cell wall provides rigidity.

The phospholipid bilayer is dynamic since the lipid molecules can move sideways and exchange places as required to repair the membrane.

Plasma Membrane proteins Plasma Membrane proteins Membrane proteins can be integral or peripheral to the cell membrane. Integral proteins extend across the phospholipid bilayer, among the fatty acid tails. Most of them are glycoproteins, combinations of sugar and proteins. The sugar portion of the molecule orients itself towards the extracellular side of the membrane. Peripheral proteins are loosely attached to both sides of the plasma membrane, and do not extend through it.

The membrane proteins vary considerably among cells and determine the functions of the cells. The proteins have a wide variety of functions. Some integral proteins act as channels, or pores that allow the passage of some molecules. Other integral

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proteins act as transporters, carrying some molecules across the cell membrane.

Integral proteins also act as receptors that can identify specific molecules such as hormones, neurotransmitters, or nutrients. These specific molecules are called the ligands of the receptor proteins.

Some integral and peripheral proteins are enzymes. Some internal peripheral proteins are cytoskeleton anchors, forming an attachment between the plasma membrane and the cytoskeleton. Membrane glycoproteins and glycolipids are often cell identity markers, enabling cells to recognize other cells of their own kind during tissue formation, and to recognize potentially harmful foreign cells. The A, B, and O blood type markers are an example of cell identity markers.

Plasma Membrane Physiology Plasma Membrane Physiology Communication is one of the primary functions of the cell membrane. As we have seen, it interacts with other cells, foreign cells, and ligands such as hormones, neurotransmitters, enzymes, nutrients, and antibodies in the extracellular fluid.The plasma membrane maintains an electrical and chemical gradient, or difference, between the inside and the outside of cells, called the electrochemical gradient (Figure 3-2). Both are essential to the healthy functioning of the cell.

A true story about HIV research AIDS research in the USA is focused almost entirely on ways to suppress replication once the HIV virus has entered cells. A drug that can do this within cells is by nature an extremely toxic drug. The one that is widely used is AZT and some close replicas, all in the chemotherapeutic category. Mainstream viral research has not focused on the way that viruses enter cells, assuming they enter by viroplexis, a vague concept of a virus glomming onto a cell’s plasma membrane and somehow gaining entry. Dr. Candace Pert is a neuroscientist who started her career in search of a natural opiate substance in our bodies. She suggested that if opiate drugs to gain entry into our cells through specific receptor sites, these sites must be there for a natural substance already in our bodies. She and other researchers identified the existence of endorphins in the 1970’s. Her research has focused since then on finding many other small informational peptide substances that are synthesized in many organs of the body and have receptor sites in many organs of the body, creating an informational network that she now equates with our bodymind. These peptides link our brain, digestive, immune and

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endocrine systems in an extensive information network, and led to the development of the new integrative field of psychoneuroimmunology. Her work lends extensive scientific support to explain how our emotions can affect our health through our immune system, as she has laid out in her book Molecules of Emotion. In 1985 Dr. Pert identified the plasma membrane proteins that are the receptor sites used by HIV to enter cells. She called them T4 receptor sites since they are found on the T4 lymphocytes of the immune system. She has also mapped their locations in the frontal cortex and hippocampus of the brain. This discovery concurs with the symptoms of AIDS: a person infected with the virus loses resistance to infections, which would result from a loss of T4 immune cells. AIDS-associated dementia, memory loss, nerve degeneration and depression could result from a loss of brain tissue. After identifying the receptor sites, Dr. Pert realized that if she could identify the natural ligand in the body that gets into cells via the T4 sites, this might be a non-toxic, natural therapy that would bind the receptor sites and prevent the HIV virus from entering cells. She identified some proteins with the same shape as the spikes on the outside of the HIV virus, and eventually found one that worked perfectly to stop replication of HIV in a test tube, which she named Peptide T. It is also known as vasoactiveintestinal peptide, or VIP. Discovery of Peptide T was a huge achievement, but also too multidisciplinary for any of the top scientists to grasp, and publication was extremely slow. There were many senior researchers that had spent years on AZT research that opposed her efforts to undermine their life work, so that eventually it became clear that no funding would be available, and she gave up her position and tenure with the National Institutes of Health to work with funding from a large drug company. After initial testing with AIDS patients, the drug company cut her funding in favor of the AZT research which was further along and well-proven. Although Peptide T did undergo some very successful double blind placebo studies at Yale University, it was not enough to get FDA approval. Peptide T has now gained popularity with AIDS activists and is being made underground and sold through buyers clubs across the US (www.ibismedical.com/notepept.html), and is now being researched at the National Institutes of Mental Health.

The chemical gradient exists because of different concentrations of chemicals inside cells and outside. The most notable are the concentrations of ions. Outside cells, the main cation is Na+ and the main anion is Cl-. Within cell cytoplasm, the main cation is K+. The main anions are organic phosphates (PO4-3 groups attached to molecules such as ATP) and negatively charged amino acids in proteins.

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The electrical gradient arises because the inside surface of the cell membrane is more negatively charged than the outside surface, resulting in a membrane potential across the membrane. This is a voltage, a form of potential energy that exists whenever there is a separation of positive and negative charges, just like in a common battery. Overall, the charge within the cytoplasm and the extracellular fluid is neutral. The voltage only exists near the plasma membrane of living cells, and ranges between –20 and –200 mV (millivolts). The negative sign refers to the outside of the cell, where there is a greater negative charge.

Selective permeability is another important quality of cell membrane physiology. It simply means that some substances pass through the membrane with greater ease or difficulty than others, and of course water passes the most easily. Substances that dissolve in lipids (non-polar, hydrophobic molecules) also pass through the mainly lipid membrane easily. Uncharged molecules that are small, even if they are polar, can also pass through. Large molecules and charged molecules cannot. Charged molecules can get through via the transport proteins; the negative membrane potential makes it much easier for cations to enter the cell.

Integral membrane proteins form channels or act as transporters to aid some polar or charged molecules across the membrane. Channels are water filled pores that allow passage of some molecules. Transporter proteins act like a ferry boat, shuttling very specific molecules across the membrane.

Passive movement of materials across Passive movement of materials across the cell membrane the cell membrane Mechanisms that move substances required by the cell and wastes from the cell without using energy are called passive systems. These include diffusion, osmosis, filtration, and facilitated diffusion. They depend on pressure or concentration differences on each side of the plasma membrane.

Simple diffusion is the movement of molecules from areas of high to low concentration until equilibrium is reached. Movement will be fastest when there is a larger gradient or more kinetic energy due to heat. Imagine what happens when you add

Figure 3.2 The electrochemical gradient

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a drop of ink to a glass of water – it slowly blends with all the water in the glass.

The substances that move through the plasma membrane by simple diffusion include water, oxygen, carbon dioxide, nitrogen, steroids, fat-soluble vitamins (A, E, D, and K), urea, glycerol, small alcohols, and ammonia. Notice that even large molecules that are fat-soluble diffuse easily. Note also that alcohol dissolves in the lipid layer, and hence enters cells very rapidly.

Some substances cannot pass through the lipid bilayer but they pass a little more slowly through the integral protein pores by simple diffusion. These include the ions Na+, K+, Ca2+, Cl-, and bicarbonate ions HCO3-.

Osmosis is the movement of water through a selectively permeable membrane, in this case the plasma membrane, to areas of lesser concentration. The plasma membrane is selectively permeable to some substances, so they will become concentrated within the cell and reduce the relative concentration of water. In this case, water will move into the cell. Water will continue to move into the cell and increase the pressure within the cell, until eventually the pressure becomes too great to allow further inflow. The pressure at this point is called the osmotic pressure. I like to think of how a tea bag grows large in hot water, but rarely develops enough internal pressure to burst the bag. In living tissue the osmotic pressure is relatively balanced inside and outside the cells.

Tonicity is the relative concentration of dissolved particles inside and outside of cells. An isotonic solution has the same concentration on each side of the cell membrane. Red blood cells are bathed in a solution of ions in the blood that is isotonic to them. In a lab, we can place red blood cells in a normal saline solution that is isotonic to them (0.9% NaCl), and the cells will not shrink or enlarge. If we place the cells in a hypotonic solution, with less NaCl, then the water will flow into the cells and we can see them enlarge. A hypertonic solution would make the cells shrivel up, which is called crenation. You can imagine that the body must maintain a precise balance of ions so that cells are not damaged, and that this can be disrupted by dehydration, excessive salt consumption, or loss of minerals through sweating.

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Filtration occurs primarily in the kidneys. Increased blood pressure forces water and small sized waste products out of the blood and into the tubules of the kidneys. The membrane of the

capillaries retains the larger protein molecules in the blood.

Facilitated diffusion is the diffusion of large, lipid-insoluble molecules from areas of greater to lesser concentration, with the help of integral transporter proteins. Glucose is the most important molecule that enters the cell in this way. When glucose attaches to a transporter protein, the protein changes shape and releases the glucose within the cell (Figure 3.3). Within the cell, the concentration of glucose is kept low by converting the glucose molecules to another molecule, glucose 6-phosphate, right away.

Facilitated diffusion of glucose is greatly accelerated by insulin, a hormone produced by the pancreas. The pancreas is stimulated to secrete insulin when blood sugar levels are elevated. Insulin then lowers glucose levels by speeding the entry of glucose into the cells.

Active movement of materials across Active movement of materials across the cell membrane the cell membrane Some molecules can only enter or leave cells through the energy consuming processes of active transport or bulk transport, described below.

In active transport, specific integral membrane proteins act as ATP-driven pumps to push certain ions and some smaller molecules across the membrane. Some ions and larger molecules that need to be transported in this manner include Na+, K+, H+, Ca2+, I-, Cl-, amino acids and monosaccarides.

There are two types of active transport: primary and secondary. In primary active transport, the integral membrane protein changes shape through the use of ATP to allow movement of molecules through the protein. In most cells, about 40% of the ATP is spent running primary active transport pumps. The lethal

Fig 3.3 Facilitated diffusion of glucose

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poison cyanide acts by shutting down active transport pumps throughout the body.

The most commonly known example of a primary active transport pump is the sodium-potassium pump. These integral proteins pump sodium ions (Na+) out of cells to maintain a low concentration within the cytoplasm. They also pump potassium ions (K+) into cells against their concentration gradient. In secondary active transport, the energy stored in ion gradients drives substances across the membrane. The gradient is established by a primary active transport pump, but the actual movement of substances is only due indirectly to the use of ATP. The sodium pump maintains a low concentration of sodium ions within the cell, creating a concentration gradient. A large gradient will cause sodium ions to leak back in, carrying other molecules. Glucose, fructose and amino acids move into cells that line the gastrointestinal tract and the kidney tubules with sodium ions in this manner. This mechanism is called symport or cotransport.

Substances can also move in opposite directions, called an antiport, or countertransport. In most cells, leakage of sodium ions into cells can expel H+ and Ca2+ out of cells. Since H+ increases acidity, antiports give cells a mechanism for maintaining a balanced pH. A balance of Na+ and Ca2+ is crucial for normal functioning of nerve and muscle cells.

Bulk transport is the second form of active transport, providing ways for moving massive materials in and out of cells. Large particles, such as whole bacteria and red blood cells, and large molecules, like polysaccharides and proteins, may enter cells by endocytosis and leave by exocytosis. Energy is derived from splitting ATP molecules.

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Phagocytosis, pinocytosis, and receptor-mediated endocytosis are three types of endocytosis, or processes to bring substances into cells. Large molecules or particles are surrounded by a segment of the plasma membrane, which envelops the substance and brings it into or out of the cell.

In phagocytosis, or cell eating, projections of plasma membrane called pseudopods surround large solid particles outside the cell. Once the particle is surrounded, the pseudopods fuse, forming a membrane sac, or vesicle, containing the particle. Phagocytosis is the mechanism used by white blood cells to engulf bacteria and other foreign substances; an important component of our immune system.

In pinocytosis, or cell drinking, the engulfed material is a tiny droplet of extracellular fluid. Rather than forming pseudopods, the cell membrane folds inward and surrounding fluid flows in. While only specialized cells carry out phagocytosis, most cells are capable of pinocytosis. Receptor-mediated endocytosis is a very selective process of taking in substances required by cells (Figure 3-4). Protein

DigitalisDigitalis The drug Lanoxin is one of many that is derived from a plant, in this case Digitalis purpurea, or purple foxglove. It strengthens the heart beat so it is given to patients with heart failure or weakened pumping action of the heart. Digitalis works by slowing the sodium pump, allowing more Na+ to accumulate inside heart muscle cells. There becomes less of a gradient, or difference in concentrations of Na+ within and outside the heart cells. This in turn slows the Na+/Ca2+ antiport, causing more Ca2+ to remain inside the cells. A greater concentration of the calcium ions within the heart muscle cells strengthens the muscle contractions of the heart.

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receptors on the cell membrane identify their specific ligands in the extracellular fluid, for example: hormones, vitamins, cholesterol, or iron. These substances then enter the cell in an endocytic vesicle, and the protein receptors are released to the cell membrane again by exocytosis. Some viruses also enter the cell by hitchhiking with ligands. The aids virus attaches itself to a glycoprotein receptor on certain types of white blood cells.

Exocytosis is the elimination of substances from the cell. These substances are packed in secretory vesicles that fuse with the cell membrane and then open to the outside, where their contents are released to the extracellular fluid. This process occurs in all cells, and in particular it is the mechanism by which nerve cells release neurotransmitters, and the way in which substances such as digestive enzymes and hormones are released from their sites of synthesis.

Figure 3.4 Receptor-mediated endocytosis

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Lesson Three Lesson Three ReferencesReferences Chiras, David. 1993. Biology: The Web of Life. Vol. I & III. St.

Paul, Minn.: West Publishing. Levine, Joseph and David Suzuki. 1993. The Secret of Life,

redesigning the living world. Toronto: Stoddart Publishing Co.

Pert, Candace B. 1997. Molecules of Emotion: why you feel the

way you feel. With a foreward by Deepak Chopra, MD. Scribner, New York.

Tortora, G. and S. Grabowski. 1993. Principles of Anatomy and

Physiology. 7th edition. New York: Harper Collins.