1. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2-1 Genetics-Chapter 2 Cells (pp 19-45)

2. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2-2 Cells The Basic Unit of Life Organisms can be single cells or collections of many cells Mutations affect whether the cell functions normally Cell numbers are important, critical to growth, development, and healing

3. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2-3 Human Cells > 260 cell types Four main categories – Epithelial – Muscle – Nerve – Connective

4. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2-4 Types of Cells Prokaryotic cells Lack a nucleus Eukaryotic cells Contain a nucleus complex organelles. 1000x the volume of a prokaryotic cell.

5. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2-5 3 Domains of Life Genetic material Domain in a compartment? Example Bacteria no (prokaryote) E. coli Archaea no (prokaryote) Methanopyrus Eukarya yes (eukaryote) 4 kingdoms amoeba, plant, human, yeast

6. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2-6 Macromolecules in Cells Carbohydratessugars, starches energy & cell structure Lipidsfats, oilsmembranes, hormones insulate, store energy Proteinsmyosin, collagenv. diverse, many functions structures, clotting, nerve transmission, muscle contractions, transport, enzymes Nucleic acidsDNA, RNAgenetic material, translates into proteins- gives cells characteristics We also need vitamins and minerals

7. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2-7 Inborn Errors of Metabolism Genetic disorders that result from deficient or absent enzymes- – Too much or too little product is produced. Carbohydrates- – Lactase deficiency- lack of lactase Build up of lactose, bacteria multiply, gas, cramps, bloating in child’s intestine. Switch to soybean-based infant formula

8. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2-8 Lipids- Familial hypercholesterolemia Gene variant that decreases by half the protein receptors for cholesterol on liver cells. Cholesterol can’t enter liver so builds up in arteries. Low fat diet, cholesterol lowering drugs

9. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2-9 Proteins: – Maple syrup urine disease Inability to digest three types of amino acids. Leads to buildup in the bloodstream. Treatment- diet Nucleic Acids: – Lesch-Nyhan Syndrome Deficiency of an enzyme –HGPRT Body cannot recycle two of the four types of DNA nucleotides. They become converted into uric acid which crystalizes in the urine Pain, writhering, severe mental retardation, kidney failure

10. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2-10 Vitamin deficiencies Biotinidase deficiency- slow use of biotin. – Without early detection and biotin supplements- mental retardation, seizures, skin rashes, loss of hearing, vision, and hair. Eventually lethal Minerals- Wilson’s disease – Excess copper – Stomachaches, headaches, hepatitis, slurred speech, loss of balance, altered handwriting. – See green rings around the iris of the eye. – Tr. Penicillamine- able to excrete copper in the urine.

11. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2-11 An Animal Cell Surrounded by the plasma membrane Contains a nucleus and cytoplasm with specialized organelles

12. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2-12 Structures and Functions of Organelles

13. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2-13 Nucleus- Most cells have 1, RBCs-0, skeletal-several. Surrounded by double layered nuclear membrane. Contains: – Nuclear pores- rings of proteins that allow movement of some molecules in and out. – Nucleolus, which is the site of Ribosome production. Disappears during mitosis. - Nucleoplasm - fluid in the nucleus. – Chromosomes composed of DNA and proteins. –Genetic material-DNA

14. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2-14

15. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2-15

16. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2-16 Secretion

17. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2-17 Endoplasmic Reticulum (ER) Interconnected membranous tubules and sacs from nuclear envelope to plasma membrane. Rough ER, closest to nucleus. contains ribosomes, site of protein synthesis Smooth ER does not contain ribosomes and is important in lipid synthesis. Quality Control

18. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2-18 Golgi Apparatus Processing center. Stacks of flat, membrane-enclosed stacks Final protein folding Stores secreted material Forms sugars, glycoproteins, and glycolipids Vesicles of material are released

19. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2-19 Lysosomes Break down bacteria, cellular debris, and nutrients Contain > 40 types of digestive enzymes Tay-Sachs is an inherited lysosomal storage disorder

20. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2-20 Peroxisomes Sacs with outer membrane that contain several types of enzymes. Function: –Break down lipids, rare biochemicals –Synthesize bile acids –Detoxify compounds from free radicals Abundant in liver and kidney cells. Lorenzo’s Oil- – adrenoleukodystrophy- absent peroxisomal enzyme. –Fatty acid buildup in brain and spinal cord. –Low blood sugar, skin darkens, muscle weakness.death. –Treatment- eating canola oil- slows the buildup of the fatty acid.

21. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2-21 Mitochondria Site of ATP (energy) production. Outer membrane, inner membrane, folds-cristae with enzymes. Has its own circular DNA. Mitochondrial genes are inherited from the mother. Sperm mitochondria is located in the middle region, not the head so they don’t enter the egg. Inherited diseases with abnormal mitochondria result in muscle weakness.

22. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2-22 Plasma Membrane Selectively permeable-monitors movement of molecules in and out of the cell. A phospholipid bilayer- hydrophobic barrier. Phosphate head -hydrophilic Fatty acid chains -2- hydrophobic Contains proteins, glycoproteins,and glycolipids Important to cell function and interactions. Molecules that extend from the plasma membrane may act as receptors- fit and hold molecules outside the cell (ligands) Some membrane proteins form channels for ions- Ca+2, Na+, K+, Cl-. There may be a few thousand channels for each ion in a plasma membrane.

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24. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2-24 Faulty Ion Channels May Cause Inherited Diseases Sodium channels – ability to detect pain.-alters channels on certain nerve cells. No pain or “burning man syndrome”-hypersensitive channels- and “paroxysmal extreme pain disorder-channels stay open too long-affects rectum, jaws, eyes. Potassium channels – Long-QT syndrome-deafness. Abnormal K+ channels in heart. muscle cells and inner ear. Fatal heart rhythm Chloride channels – Cystic fibrosis. CFTR protein remains in the cytoplasm unable to reach the plasma membrane. Also disrupts Na+ channels so salt trapped inside cells draws in moisture. Cells lining the lungs and ducts of the pancreas. Symptoms- difficulty breathing, respiratory infections, digestion- buildup of thick mucous.

25. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2-25 Cytoskeleton A meshwork of protein rods and tubules. 3 types- –Microtubules, –Microfilament –Intermediate filaments. associated proteins Dynamic- cells are perpetually building up and breaking down microtubules. Functions: Maintain cell shape Connect cells to each other Transport organelles and small molecules Provide cell motility (some cell types) Move chromosomes in cell division Compose cilia

26. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2-26 Cytoskeleton

27. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2-27 Intermediate filaments- actively dividing skin cells of upper skin layer.- – Inherited disease- epidermolysis bullosa- abnormal intermediate filaments- skin blisters easily. Hereditary spherocytosis- disturbed interface between plasma membrane and the cytoskeleton in rbcs. The rbc balloons out obstructing narrow blood vessels-anemia, fatigue, weakness. –Treatment- remove spleen

28. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2-28 Cell Division and Death Are required for normal growth and development. Mitosis produces new cells –Mitosis occurs in somatic cells (all cells but egg and sperm) Apoptosis is cell death that is part of normal development Necrosis is cell death in response to injury

29. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2-29 Figure 2.12

30. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2-30 The Cell Cycle The sequence of events associated with cell division S phase : DNA synthesis G phase : gap for growth M phase : mitosis (nuclear division) Cell division or cytokinesis follows Figure 2.13

31. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2-31 Stages of the Cell Cycle Interphase-90% of time –Prepares for cell division –Replicates DNA and organelles –Composed of G 1, S, and G 2 –Cells may progress to mitosis or enter G 0, a quiescent phase Mitotic Phase: 10% of time – Mitosis division of the nucleus – Cytokinesis division of the cytoplasm

32. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2-32 Replication of Chromosomes Process of duplicating a chromosome Occurs prior to division, during S of interphase Produces sister chromatids Held together at centromere Figure 2.14

33. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2-33 Mitosis Produces two identical daughter cells Replicated chromosomes align Sister chromatids separate and move to opposite poles. Nuclear membranes form around each new nucleus Division of cytoplasm or cytokinesis occurs.

34. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2-34 Overview of Mitosis Continuous process divided into Prophase Metaphase Anaphase Telophase

35. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2-35 Mitosis in a Human Cell Figure 2.15

36. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2-36 Prophase Replicated chromosomes condense Microtubules organize into a spindle Nuclear membrane breaks down Figure 2.15

37. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2-37 Metaphase Chromosomes line up on the metaphase plate Spindle microtubules are attached to centromeres of chromosomes Figure 2.15

38. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2-38 Anaphase Centromeres divide Chromosomes move to opposite ends of the cell Figure 2.15

39. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2-39 Telophase Chromosomes uncoil Nuclear membranes form Spindle disappears Figure 2.15

40. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2-40 Cytokinesis Cytoplasmic division occurs after nuclear division is complete. Two cells are formed.

41. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2-41 Cell Cycle Control Proteins called “checkpoint proteins” monitor progression through the cell cycle. Figure 2.16

42. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2-42 Telomeres Located at the ends of the chromosomes Contain hundreds to thousands of six nucleotide repeats Most cells lose 50-200 repeats after each cell division After about 50 divisions, shortened telomeres signal the cell to stop dividing Sperm, eggs, bone marrow, and cancer cells produce telomerase that prevent shortening of telomere

43. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2-43 Apoptosis Orderly destruction, stepwise process –Caspases destroy cellular components, signal phagocytes to clean up Mitosis and apotosis work together to form functional body Cancer can result from too much mitosis, too little apotosis. Imbalance

44. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2-44 Apoptosis Programmed cell death is part of normal development Figure 2.18

45. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2-45 Cell-Cell Interaction: Signal Transduction The process of transmitting a signal from the environment to a cell Figure 2.19

46. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2-46 Signal Transduction Receptor binds to messenger Interacts with regulator Causes enzyme to produce second messenger Activates enzymes Amplification due to cascade Defects cause disease

47. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2-47 Cell-Cell Interactions: Cell Adhesion Molecules (CAMs) Figure 2.20 In inflammation cell adhesion molecules guide wbcs to injury sites. Leukocyte adhesion deficiency and cancer are disorders that can result from abnormal cell adhesion.

48. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2-48 Stem Cells and Cell Specialization Stem cells and progenitor cells renew tissues –Stem cells can yield identical stem cells –Stem cells can yield partially specialized progenitor cell. Retain the ability to divide and specialize Described in terms of potential –Totipotent-give rise to every cell type- fertilized egg or very early embryo –Pluripotent-later in development- give rise to fewer cell types. As specialization occurs some genes are expressed and some genes are ignored- –Bone cells and muscle cells produce different proteins resulting in different functions. –All cells must have proteins for basic cell maintanence.

49. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2-49 Figure 2.22

50. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2-50 Medical Treatments Using Stem Cells Regenerative medicine- using stem cells to treat disorders or injuries with cells that can divide. Human embryonic stem cells : Sources- Early embryos from fertility clinics Human embryonic stem cells- from an 8-celled embryo or 5- day blastocyst- can give rise to any cell type. Must be typed. Controversial. Somatic cell nuclear transfer- uses a nucleus from a somatic (body cell) from a patient with an injury. The nucleus is injected into a donated egg cell which has its nucleus removed. Cloning. The resulting cell develops into a 8- celled or blastocyst stage and the needed cells are removed and used. A genetic match- no typing is required. Not done at this time- we need to still understand how organs are formed from cells. One issue- obtaining human eggs.

51. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2-51 Figure 2.24

52. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2-52 Tissue-based (adult) stem cells- non- embryonic Restricted in the types of specialized cells they give rise to. Examples- – bone marrow transplants, –stored umbilical cords- blood disorders. Not all organs have stem cells.

53. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2-53 Much more to learn about stem cells What makes a stem cell a stem cell? 80 genes have been identified that are involved in a cell being a stem cell – Involved in signal transduction – These genes are also found and expressed in non stem cells???? – More research on the genome will eventually unlock how genes enable a cell to retain the developmental potential.