BIOL 237 Class Notes - Review of Chemistry and Biology

Introduction, Chemistry Review, Cell Biology Review
The first portion of these notes are totally for review and will not be covered in lecture, nor specifically tested.

The scope of anatomy & physiology, the study of the structures and functions of the human body:
Structure and function are directly related to one another, i.e. each determines the other. This concept is called their complementarity.
The structures: known as the Hierarchy of living organisms.
   Cells - the simplest structures capable of performing all living functions.
   Tissues - groups of cells working together to perform specific functions.
   Organs - tissues working together to perform specific functions.
   System - a group of organs working together to perform specific functions.
This hierarchy illustrates specialization and division of labor which permits the existence of complex organisms such as man.
The Functions of Life.
    1. Maintaining boundaries and integrity of the organism - illustrated at the cellular level by the cell membrane and at the organism level by the skin.
    2. Movement - includes molecular transport, as in the exchange of nutrients and wastes, and movement of the organism or its parts, as in muscular contractions.
    3. Responsiveness, irritability, excitability - includes chemical, electrical, and physical responses to stimuli. Illustrated by chemical events at cell membranes and nervous control of muscle contraction and other body functions.
    4. Intake of nutrients and digestion - all organisms must take in nutrients and process them. Nutrients include necessary gases such as oxygen or carbon dioxide.
    5. Metabolism - the sum of energy producing and energy utilizing chemical reactions. Metabolism converts the energy in nutrients to usable forms and couples that process with energy-requiring processes.
    6. Excretion - removal of waste products from the above processes.
    7. Growth and repair - organisms must be able to grow to maturity and to maintain and repair damaged tissue in order to survive.
    8. Reproduction - organisms must be able to reproduce in order to perpetuate the species.

Homeostasis - defined as a dynamic balance of processes and materials in the organism. Homeostasis involves response to stress to maintain a narrow range of conditions, thus sustaining life.
    Most homeostatic mechanisms utilize a control system known as negative feedback. (See Figure 1.4) Negative feedback works like a thermostat. A sensor responds to a variable stimulus. When that variable is outside the normal range the sensor notifies a control center, which then responds directly or triggers a response by an effector. The response has the effect of reducing or negating the original stimulus by bringing the variable back within the normal range. A negative feedback mechanism is self regulating, it turns itself off.
    Very few processes in the body involve positive feedback and those that do use it to produce a quick response. Some external mechanism is necessary to turn off the process. Examples of positive feedback include: blood clotting, the labor contractions of childbirth, digestion in the stomach.

Chemical constituents of cells of the human body:
   Protoplasm of cells contains water (the major component of all body fluids), electrolytes, O₂, CO₂, and macromolecules.
   Extracellular fluid - fluid outside the cells including interstitial fluid (tissue fluid) and blood, together with other specific fluids such as urine and cerebrospinal fluid. The extracellular fluid is a part of the extracellular matrix (ECM).
   Intracellular fluid - the fluid inside cells, also known as the cytosol.
    Predominant electrolytes in intracellular fluid are K⁺, Mg⁺², Ca⁺², H⁺, PO₄^-3, SO₄^-2, HCO₃^-.
    Predominant extracellular electrolytes are Na⁺, Cl^-, H⁺.   Ca⁺² and HCO₃^- also important extracellularly in certain locations.
    H⁺ and HCO₃^-are important in regulating pH. Hydrogen ions are acid ions and lower the pH of a solution. The pH is important for normal structure and function of proteins. In the human body bicarbonate ions help to neutralize hydrogen ions to maintain a normal pH range. A chemical reaction between carbon dioxide and water in the blood produces carbonic acid in equilibrium with hydrogen ions and bicarbonate. This produces a buffer which maintains the normal pH of the blood.

Chemical bonds (See Figure 2.8):
   Ionic bonds - result from gain or loss of electrons between atoms. This produces ions or electrolytes as above. Ionic bonds are broken when the substance dissolves in water.
   Covalent bonds - these bonds are produced when electrons are shared between atoms.
   Polar covalent bonds result when the sharing is unequal. Examples are water and functional groups of most organic molecules such as carboxylic acids, amines, etc. Polar molecules have charged portions which attract opposite charges and other polar molecules. Polar molecules and groups tend to be hydrophilic, i.e. they attract water and orient themselves toward aqueous solutions.
   Non-polar covalent bonds result when the sharing is equal or the molecule is symmetrical, thus canceling the polarity. Examples include carbon dioxide and long chain hydrocarbons. Non-polar molecules and groups tend to be hydrophobic, i.e. they repel water and orient themselves away from water and aqueous solutions.
The hydrophilic and hydrophobic nature of proteins and other molecules plays a large role in the conformation (shape) and position in cell membranes and other structures, as well as their functions. Interactions form between molecules and groups of like polarity or non-polarity.
   Hydrogen bonds - are electrical attractions between NH⁺ and C=O^- groups found at distances on the same molecule or on different molecules. Hydrogen bonds cause coiling of proteins and hold the strands of the DNA molecule together, among many examples.

Macromolecules are large complex molecules made from simpler subunits. There are also intermediate levels of structure.
   Carbohydrates: (See Figure 2.13) simple subunits are monosaccharides or simple sugars such as glucose, fructose, and galactose. Each is a sugar with a molecular formula of C₆H₁₂O₆. But their structural formulas differ. They are combined by dehydrolysis (dehydration synthesis) to form chains.
   Dehydrolysis (a.k.a. dehydration synthesis) - the chemical combination of simple molecules into complex forms with the accompanying release of a molecule of water.
    Two combined in this way (a glycosidic linkage) produce a disaccharide. Two glucose units form maltose, a glucose and a fructose produce sucrose (table sugar), a glucose and galactose form lactose (milk sugar). Continued combining to form a long chain produces a polysaccharide. Polysaccharides include starch and glycogen which are used as stored fuel in plants and animals respectively. The difference between starch and glycogen is the amount of branching with glycogen being the most highly branched. Cellulose also consists of glucose units but the linkage differs from that in starch and glycogen and cannot be digested by most animals. For humans cellulose is indigestible fiber, an important component of our diet, but not used for food. Only microorganisms have the necessary enzymes. Termites and other animals that eat wood, grass and the like have the microorganisms in their guts which perform the digestive process known as hydrolysis.
   Hydrolysis - the splitting of a complex molecule into its subunits by the chemical addition of a molecule of water.
    Other intermediates: these are intermediates in digestion and are also synthetically produced for use in energy bars and other "athletic foods".
   dextrins are short portions which include the branch points of polysaccharides.
   oligosaccharides are usually 3 to 8 glucose units long, but may be longer. Oligosaccharides are important in attaching to lipids and proteins in the cell membrane to form a glycocalyx. These oligosaccharides are composed of monosaccharides other than glucose (see below) and can be quite variable in structure. This gives them uniqueness which is part of the cells identity.
Use of carbohydrates in the human body:
   Glucose is the primary fuel for most cells and the nearly exclusive fuel for most nervous system cells. Anerobic muscle fibers (those important for strength and speed) depend mostly upon glucose and store glycogen for rapid hydrolysis to glucose. Glycogen is also stored in the liver.
    The carbohydrate portions of glycoproteins and glycolipids are part of the glycocalyx or "sugar coating" many cells have. This layer is part of the recognition system by which cells are identified by other cells such as those of the immune system, and it functions as a protective coating for some cells. Proteoglycans are molecules with a core protein and attached glycosaminoglycans (GAGs). See [The Structure of a Proteoglycan Complex]. GAGs are composed of aminated (containing amine groups) and sulfated (containing sulfate groups) disaccharides and are important to the structure and function of many tissues and the extracellular matrix (ECM). [See histology ]. Glycosaminoglycans include hyaluronic acid, heparan sulfate (gives rise to heparin), keratan sulfate (gives rise to keratin), glucosamine, and chondroitin sulfate. Other glycoproteins include collagen, elastin, and reticular fibers.

   Proteins - made of amino acid subunits combined by dehydrolysis (See Figure 2.16). The bond between amino acids is called a peptide bond and unites them through a nitrogen atom. There are about 20 naturally occurring amino acids in the body, (See Figure 2.15) eight of which, called essential amino acids, must be included in the diet. The others may be manufactured from one another by the liver. Two amino acids combined produce a dipeptide, more produce a polypeptide. A protein is a polypeptide of 100 amino acids or more.
Proteins exhibit 4 levels of structure: (See Figure 2.17)
    1^o - primary level of structure: the amino acid sequence. This sequence determines the characteristics of the protein and the possibilities are virtually unlimited. All proteins have a primary level of structure.
    2^o - secondary level of structure: the formation of the alpha-helix. Proteins will coil due to hydrogen bonding between (NH⁺) and (C=O^-) groups on amino acids about four distant. The coils permit protein chains to entwine and braid producing strength especially important in structural proteins. Beta pleated sheets are also a form of secondary structure, which permits proteins to form a planar network (like a flat plane). This is especially important in proteins in the basement membrane of epithelial tissues for instance. All proteins have a secondary structure, but proteins such as collagen (See Figure 2.18), keratin and elastin are examples of protein having a secondary level of structure which is particularly important for their functions in the body.
    3^o - tertiary level of structure: the formation of a specific three-dimensional or globular structure. Tertiary structure results from bending and folding due to hydrogen bonding and the formation of disulfide bonds between cysteine molecules. Because of tertiary structure, proteins can adopt a very precise shape, which is individual to each specific protein. This allows them to act as enzymes, receptors, carriers and the like, molecules which must have a lock-and-key relationship with their substrates or stimulating molecules. (See Figure 2.21). Examples of globular proteins are actin and myosin (proteins important to movement), carrier proteins such as transferrin, which carries iron in the blood, various hormones, enzymes, and other substances such as antibodies.
    4^o - quaternary level of structure: These proteins have a complex structure and complex functions to match. They are multi-chained (chains must be different) with non-protein cofactors. Hemoglobin is the best known example with several different proteins in its globin part and non-protein heme groups which contain ion atoms for carrying oxygen. Hemoglobin plays a role in both oxygen and carbon dioxide transport and is efficient at loading and unloading these gases.

Lipids: lipids is a category encompassing all lipid-soluble substances, including fats, steroids, prostaglandins, eicosanoids, etc.
   Fats: Fats are comprised on a glycerol backbone with one, two, or three attached fatty acids (See Figure 2.14). They are stored in the fat reserves of the body for fuel and present as phospholipids in the cell membrane. They are also called mono, di, or triglycerides depending on how many fatty acids are attached (one, two, or three respectively). Fatty acids can vary in length from 4-C to 24-C hydrocarbon chains. If all of these have single bonds (-C-C-) and therefore all possible side bonds have attached hydrogen atoms the fat is said to be saturated. If one or more bonds are double (-C=C-) then the fat is unsaturated. Saturated fat in the diet leads to atherosclerotic plaque in the arteries and diseases such as heart disease and stroke. Saturated fats come mostly from animal fats and are solid at room temperature. Unsaturated fats tend to be metabolized and to not contribute to the artery clogging plaque. Unsaturated fats derive mostly from plant oils and are liquid at room temperature.

A special version of fat is the phospholipid found in cell membranes (See Figure 2.14). Phospholipids and other fats have a polar and a non-polar end. This enables them to act as barriers between aqueous solutions. They line up with their polar "heads" (the hydrophilic glycerol-acid end) toward the water molecules, and their non-polar tails (the hydrophobic fatty acid end) away from the water. In the cell's membranes they form a phospholipid bilayer which separates the solutions and chemical reactions.

The unit membrane: (See Figure 3.2)
    The unit membrane structure, found in the plasma membrane and membrane-bound organelles, is composed of a "fluid mosaic" made up of a phospholipid bilayer with embedded globular proteins. There are integral proteins which act as receptors or carriers or ion channels, and peripheral proteins which might aid in those functions. (See Figure 3.3) The fluid mosaic concept reflects the fact that this membrane is fluid and changeable and the proteins may move, may increase or may decrease in number and extent. Many of the proteins and lipids are attached externally to carbohydrate and are designated as glycoproteins or glycolipids. The attached carbohydrates form a glycocalyx or "sugar coating" on many cells, especially epithelial cells. Actin fibers on the inside of the cell membrane produce a cytoskeleton which helps to hold the membrane shape and position.
The unit membrane:
    1) Separates solutions and chemical reactions. It compartmentalizes the cell by forming organelles and the plasma membrane.
    2) Allows passive transport by acting as a semipermeable membrane. a) Water soluble substances must pass through the protein channels of the membrane and are restricted according to size or other characteristic. b) Fat soluble substances can pass through the lipid matrix regardless of size.
    3) Performs active transport and regulates distribution of molecules and ions across the membrane.
    4) Responds to stimuli.
     5) Functions for synthesis and metabolism. Membranes produce sites which are separated from the rest of the cell that contain enzymes for specialized processes.

See [Membrane Channels and Excitability] for more information on how the protein channels and other membrane proteins regulate transport and how this produces the cell's polarity and resting membrane potential. This material won't be tested directly but is integral to understanding how cells work in, for example, the muscular and nervous systems.
(See Figures 3.6, 3.9, 3.10, 3.11, 3.12, 3.13 for methods of transport)
The relationships of the cell's membranes is shown in Figure 3.21, the Endomembrane System.

The Cell:
Organelles (tiny organs) perform the living functions for the cell.
The following are membrane-bound organelles, made of the unit membrane structure.
   Nucleus - (Figure 3.26) contains the DNA. DNA is uncoiled as chromatin (See Figure 3.27) when the cell is not dividing. This is the form in which its message can be transcribed to produce m-RNA. DNA replicates and then coils to produce chromosomes prior to cell division. The m-RNA takes the code to the ribosomes where translation results in protein synthesis. The nucleus is surrounded by the nuclear envelope, a double-layered membrane which connects to the endoplasmic reticulum.
   Nucleolus (-i pleural) - found in a characteristic number in certain cells. The nucleoli are the source of ribosomal RNA.
   Ribosomes are the location of protein synthesis. They may be free in the cytoplasm, in which case they make proteins for use inside the cell. Or they may be attached to the endoplasmic reticulum (therefore called the rough endoplasmic reticulum, in which case its proteins will be processed to make substances for secretion by the cell.
    The endoplasmic reticulum (Figure 3.16) comes in rough and smooth. The rough E.R. makes substances used mostly for cellular secretion. The proteins are made by the attached ribosomes. The smooth endoplasmic reticulum makes and processes non-protein substances, also often for secretion by the cell. Smooth endoplasmic reticulum is also responsible for detoxification of many substances taken in by the cell, and is the location of carbohydrate metabolism including glycolysis. The endoplasmic reticulum is a series of membrane channels within the cell.
   Golgi bodies ( Golgi apparatus, Figures 3.18, 3.19) assemble the substances into vesicles (small membrane sacks) for secretion, or as lysosomes which are used internally. Vesicles excrete substances by exocytosis, a process in which vesicles move to the cell membrane and fuse with it, releasing substances to the outside of the cell. (See Figures 3.10 and 3.11)
In addition to diffusion and osmosis, substances are brought into the cell by endocytosis, (See Figure 3.12) a process which forms vesicles, in the reverse mechanism to exocytosis. Water and dissolved substances are brought in by bulk endocytosis or pinocytosis (cell drinking), while particulates such as bacteria and cellular debris are brought in the phagocytosis (cell eating). Receptor mediated- endocytosis functions to bring specific substances into the cell. This process may be active or passive. A passive form known as facilitated diffusion is important to the transport of substances such as glucose into muscle and adipose cells. A specialized transporter (Glut-4) is used which relies of insulin to be made available in the cell membrane.
Other important transport mechanisms to review are the sodium-potassium pump, an example of direct active transport, and co-transport, an indirect active transport mechanism.
The processes of endocytosis and exocytosis are very important to a wide variety of cells. Examples include the lining cells of the GI tract, cells of the walls of capillaries, and certain white blood cells and macrophages which perform the latter in defending the body against pathogens. Lysosomes contain digestive enzymes used to break down phagocytized particulates when the lysosome fuses with the phagocytic vesicle. Peroxisomes are vesicles containing peroxidase enzymes and are important both to detoxification of substances taken into the cell, and to the normal self-destruction of cells, called apoptosis.
   Mitochondria - (Figure 3.15) are the site of aerobic metabolism of foods to produce ATP. They contain the enzymes and cytochromes for the Krebs cycle, electron transport system, and other pathways. Mitochondria also contain their own DNA, are the only organelles other than the nucleus to contain DNA, and replicate independently. Aerobic training stimulates skeletal muscle mitochondria to divide to increase the ability of these cells to perform aerobic metabolism.

Cell Surface Modifications and Non-membraneous structures:
   Cilia - hair-like processes on the apical surface of some epithelial cells which function to move mucus or fluid along the cell surface. The mucus helps to remove particulates and the like, from the respiratory system for example. Cilia are made of microtubules (See Figure 3.22) in a somewhat similar arrangement to those in basal bodies and centrioles. These microtubules link by means of motor proteins to shorten and produce a coordinated wave-like movement.
   Basal bodies anchor and control movement of cilia. They have microtubules in a specific arrangement (See Figure 3.25) and are derived from centrioles.
   Flagellum (-a) - the tail-like process which aids in sperm motility.
   Centrioles - (Figure 3.24) are structures within the cell which attach to spindle fibers to move the chromosomes during cell division. Centrioles are also made of the same microtubule array as seen in basal bodies and similar to the cilia and flagella.
   Microvilli - These are cytoplasmic processes that extend from the cell's surface. They vary from irregular and small in some cell types, to tall, closely packed, uniform projections that provide enormous surface area of other cells. Microvilli are more abundant and uniform in cells whose primary function is secretion and absorption. Stereocilia are simply unusually long microvilli. Microvilli are typically supported internally by actin filaments.
The cytoskeleton and other supporting components:
   microfilaments: composed of thin actin filaments. These are found beneath the plasma membrane where they aid in cell shape and movement (e.g. in macrophages which exhibit amoeboid movement). [See also the zona adherens below.]
   Intermediate filaments - these are keratin filaments which primarily form the desmosomes and hemidesmosomes.
   Microtubules - made of tubulin protein, a globulin protein, arranged into coils which produce the tubules. Microtubules are important for support and for transport within the cell.

From this point notes will reflect lecture coverage and will be subject to testing.

Cell junctions: (See Figure 3.4: [4th Edition|5th Edition]
    Epithelial cells, certain muscle cells, and others which lie side by side have specialized connections between them, called a junctional complex. In epithelium this connection is particularly significant because it allows a sheet of cells to create a barrier or semipermeable membrane, thus compartmentalizing a tissue and restricting passage of substances across the epithelium.
   Tight junctions (a.k.a. zona occludens) are most important in restricting transport across an epithelial membrane, for instance in the wall of a capillary. Tight junctions are fusions of adjacent plasma membranes and vary somewhat in how "tight" they are. Depending on the extent and complexity of the fusions, some allow water and small molecules to pass through gaps between them (e.g. in the kidneys), and others allow very little to pass. In this way tight junctions allow these epithelial sheets to act as semipermeable membranes. [Diagram]
   Desmosomes are anchoring junctions with keratin filaments (a.k.a. intermediate filaments) running between the cells. These filaments often run across the cell laterally and are important in tissues where the cells are subjected to lateral stress, such as the skin or lining of the urinary bladder. Desmosomes are also known as macula adherens and are like spot welds between adjacent cells (macula is Latin for 'spot'). Hemidesmosomes (half-desmosomes) are small bundles of keratin filaments which anchor the basal membrane of an epithelial cell to the underlying connective tissue. There are also zona adherens which are more continuous adhesions composed of joining proteins that anchor cells to one another near the apical end (these proteins are called catenins, see also cadherin) and also connect to the actin microfilaments of the cell's cytoskeleton.
   Gap junctions have channels called "connexions" which allow ions and, therefore, electrical impulses to pass from one cell to the next. Gap junctions are found in many tissues, but the best example is between cardiac muscle cells in the heart and smooth muscle cells in the intestine.

Revised: January 17, 2005

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