The Cellular Level of Organization

1. The Cellular Level of Organization

2. The Generalized Animal Cell A cell is the basic, living, structural and functional unit of the body. Cytology is the branch of science concerned with the study of cells. The principal parts of a cell are: Plasma (or cell) membrane Cytosol Organelles Inclusions

3. Plasma or Cell Membrane The plasma membrane (also called the cell membrane or plasmalemma) surrounds the cell and separates it from other cells and the external environment. It is composed primarily of phospholipids, arranged in a bilayer and proteins. Other lipids include glycolipids and cholesterol.

4. Plasma or Cell Membrane The proteins are of two types: 1. Integral Proteins: Extend across the phospholipid bilayer among the fatty acid tails and are nearly all glycoproteins. 2. Peripheral Proteins: Do not extend across the phospholipid bilayer; they are instead loosely attached to the inner and outer surfaces of the membrane and easily separated from it.

5. Roles of Membrane Proteins Membrane proteins are enormous in variety and have many roles� Channels (pores) Transporters (carriers) Receptors Enzymes Cytoskeleton Anchors Cell Identity Markers

6. Membrane Physiology The plasma membrane functions in cellular communication, establishment of an electrochemical gradient and selective permeability.

7. Membrane Physiology The membrane�s selective permeability restricts the passage of certain substances. Substances can pass through the membrane depending on several factors that relate to the structure of the membrane: A. Lipid solubility B. Size of particles of the substance C. Electrical charges of the substance D. Presence of channels and transporters

8. Movement of Materials Across the Plasma Membrane Materials must be moved into and out of cells on a continual basis to support cellular needs for molecular synthesis, waste and toxin removal and mobilization of cellular products when necessary.

9. Movement of Materials Across the Plasma Membrane Mechanisms that move substances across a membrane without using energy (released by splitting ATP) are passive processes. Passive processes depend on the concentration of substances and their kinetic energy.

10. Movement Across the Plasma Membrane: Passive Processes Simple Diffusion: the net movement of molecules or ions from an area of higher concentration to an area of lower concentration until an equilibrium is reached. e.g. Movement of oxygen/CO2 between blood and cells and between blood and air in the lungs during breathing.

11. Movement Across the Plasma Membrane: Passive Processes Osmosis: The movement of water through a selectively permeable membrane from an area of higher water concentration to an area of lower water concentration. Osmotic pressure is an important force in the movement of water between various compartments of the body. Because osmotic pressure on both sides of a cell membrane is normally equal, the cell volume remains relatively constant.

12. Effects of Osmosis Osmosis may also be understood by considering the effects of different water concentrations on cell shape: In an isotonic solution, red blood cells maintain their normal shape. In a hypotonic solution, red blood cells undergo hemolysis. In a hypertonic solution, red blood cells undergo crenation.

13. Isotonicity & Body Fluids Red blood cells and other body cells may be damaged or destroyed if exposed to solutions that deviate significantly from isotonicity. It is for this reason that most intravenous (IV) solutions given to patients are isotonic to their red blood cells.

14. Filtration Filtration: The movement of water and dissolved substances across a membrane due to gravity or hydrostatic pressure. An example would be the kidneys which are a site of filtration.

15. Facilitated Diffusion Facilitated Diffusion: Where certain molecules, such as glucose, move through the membrane with the help of a transporter.

16. Active Processes Active Processes: Depend on the use of ATP (for energy) by the cell. The two principal types are: *Active Transport *Bulk Transport

17. Active Transport Active Transport: The movement of ions across a cell membrane from lower to higher concentrations using energy derived from ATP directly, which is primary active transport or indirectly via secondary active transport.

18. Active Transport The most prevalent primary active transport pump is the sodium pump, also called the Na+/K+ pump. Secondary active transport mechanisms may be symports or antiports (see your text.)

19. Rx: Digitalis Digitalis, a drug given to strengthen the heart beat of patients with cardiac disease that is derived from the foxglove plant, exerts its effect by slowing the sodium pump which allows more sodium and calcium to accumulate in heart muscle cells. The increased Ca+ concentration has a positive effect on the force of cardiac muscle cell concentration.

20. Movement of Larger Substances Larger substances move across the plasma membrane by several types of bulk transport.

21. Methods of Movement Phagocytosis: the ingestion of solid particles. It is an important process used by white blood cells to destroy bacteria in the body. Pinocytosis: the ingestion of extracellular fluid. Most cells in the body are capable of this process while phagocytosis is limited to a just a few types of cells.

22. More Methods of Movement Receptor-Mediated Endocytosis: the selective uptake of large molecules and particles or ligands by the cell. Exocytosis: membrane enclosed structures called secretory vesicles form inside the cell and fuse with the plasma membrane. They release their contents into the extracellular fluid.

23. Liposomes Liposomes are artificially created membrane-like phospholipid sacs that enclose small quantities of drugs. Their purpose is to prolong the circulation of the therapeutic agent in the blood and reduce its toxicity to healthy cells. This is done by taking advantage of the cell�s natural endocytotic and absorbtive capabilities. An example: Using low-density lipoprotein (LDL) particles into which anticancer drugs have been incorporated.

24. Cytosol Cytoplasm: the substance inside the cell between the plasma membrane and the nucleus. It contains inclusions and dissolved solutes. This semi-fluid portion is called the cytosol or intracellular fluid. Cytosol is composed of mostly water but includes proteins, carbohydrates, lipids and inorganic substances. The chemicals in the cytosol are either in a suspended form (colloid) or in solution. Functionally, the cytosol is the medium in which many metabolic reactions occur.

25. Organelles Organelles are permanent, specialized structures that have characteristic appearances. They play specific roles in cellular growth, maintenance, repair and control.

26. Nucleus Usually the largest organelle, it controls cellular activities and contains the genetic information. Most cells have a single nucleus. Red blood cells have none whereas skeletal muscle cells have several. The parts of the nucleus include: the double nuclear envelope (membrane), nucleoli and genetic material (DNA) which composes the chromosomes. Chromosomes consist of subunits called nucleosomes that are composed of DNA and histones.

27. Ribosomes Ribosomes are tiny spheres consisting of ribosomal RNA (rRNA) and several ribosomal proteins. They occur freely (singly or in clusters) or together with the endoplasmic reticulum. Functionally, ribosomes are the sites of protein synthesis.

28. Endoplasmic Reticulum The endoplasmic reticulum (ER) is a network of membrane-enclosed channels continuous with the nuclear membrane. Rough (granular) ER has ribosomes attached to it. Smooth (agranular) ER has no ribosomes attached. The ER transports substances, stores newly synthesized molecules, synthesizes and packages molecules, detoxifies chemicals and releases Ca+ ions involved in muscle contraction.

29. Golgi Complex The golgi complex consists of four to six stacked, flattened membranous sacs or cisterns referred to as cis, medial and trans. The principal function of the Golgi complex is to process, sort and deliver proteins and lipids to the plasma membrane, lysosomes and secretory vesicles.

30. Cystic Fibrosis Faulty routing of a specific pump protein from the nucleus through the Golgi Complex or ER appears to be the cause of a membrane transport deficiency resulting in Cystic Fibrosis. One of the main symptoms is excessive mucus build-up in the respiratory passages.

31. Lysosomes Lysosomes are membrane-enclosed spherical vesicles that contain digestive enzymes and are formed by the Golgi complex. They are found in large numbers in WBC. Lysosomes function in intracellular digestion, digestion of worn-out organelles (autophagy) and digestion of cellular contents (autolysis) the latter which takes place during embryological development.

32. Tay-Sachs Disease (TSD) Tay-Sachs disease, in its classical form is a fatal genetic disorder in children that causes progressive destruction of the central nervous system. Affected babies appear healthy at birth and seem to develop normally for the first few months of life. After this time, development slows and symptoms begin.

33. Tay-Sachs Disease: History The disease is named for Warren Tay (1843-1927), a British ophthalmologist who in 1881 described a patient with a cherry-red spot on the retina of the eye. It is also named for Bernard Sachs (1858-1944), a New York neurologist whose work several years later provided the first description of the cellular changes in Tay-Sachs disease. Sachs also noted that most babies with Tay-Sachs disease were of eastern European Jewish origin.

34. Tay-Sachs Disease: Symptoms Babies with Tay-Sachs lack an enzyme called hexosaminidase A (hex A) which is necessary for breaking down fatty substances in brain and nerve cells. These substances build up and gradually destroy brain and nerve cells, until the central nervous system stops working. Symptoms of classical Tay-Sachs appear at 4-6 months of age when an apparently healthy baby gradually stops smiling, turning over, grasping and crawling. Then the child becomes blind, paralyzed and unaware of its surroundings. Death occurs usually by age 5.

35. Tay-Sachs Disease: Cause Tay-Sachs Disease is inherited. A Tay-Sachs carrier, who leads a normal, healthy life, has one normal gene for hex A and one Tay-Sachs gene. When two carriers become parents, there is a 25% chance that any child they have will inherit a Tay-Sachs gene from each parent and have the disease, a 25% chance their child will be free of the disease and not a carrier, and a 50% chance that a child will be a carrier.

36. Tay-Sachs Disease: Treatment There is no cure and no treatment for Tay-Sachs. Affected children can only be made as comfortable as possible. Children afflicted with this disease usually die by the age of 5 years.

37. Tay-Sachs Disease: Frequency Tay-Sachs has been almost completely eradicated. In 2003, ten babies were born in North America in 2003 with Tay-Sachs, but not a single one was Jewish. In 2004, no baby was born in North America with Tay-Sachs. Just one baby was born with Tay-Sachs in Israel in 2003, and no babies were born with Tay-Sachs in Israel in 2004.

38. Tay-Sachs Disease: Carrier Frequency Approximately one in every 27 Jews in the United States is a carrier of the TSD gene. There is also a noticeable incidence of TSD in non-Jewish French Canadians living near the St. Lawrence River and in the Cajun community of Louisiana. By contrast, the carrier rate in the general population as well as in Jews of Sephardic origin is about one in 250.

39. Tay-Sachs Disease: The Future The disease appears to have disappeared almost completely from among the Jewish nation for two reasons: In Israel, at the expense of the state, the general public is advised to carry out genetic tests to diagnose the disease before the birth of the baby. If an unborn baby is diagnosed with Tay-Sachs, the pregnancy is usually terminated. The ultra-Orthodox Jewish association Dor Yesharim tests young couples to check whether they are genetically "suitable." If both the young man and young women are Tay-Sachs carriers, the match is determined to be unsuitable and the couple split up.

40. Peroxisomes Peroxisomes are similar in structure to lysosomes but are smaller. They contain enzymes (such as catalase) that use molecular oxygen to oxidize various organic substances.

41. Additional Terms To Study: Mitochondria Cytoskeleton Flagella Cillia