Journal Activity Chapter 2 – What abnormality at the cellular or molecular level lies behind each of the following disorders? (a) cystic fibrosis (b) neurofibromatosis and (c) syndactyly.

Introducing Cells Cellular activities and abnormalities underlie our inherited traits, quirks, and illnesses Understanding genetic diseases can suggest ways to treat the condition Figure 2.1 Lack of dystrophin An early sign of DMD is overdeveloped calf muscles that are a result in the inability to rise from a sitting position in the usual way. Lack of dystrophin causes skeletal muscle cells to collapse when they contract.

Introducing Cells Our bodies include more than 260 cell types Somatic (body) cells have two copies of the genome and are said to be diploid Gametes, sperm and egg cells have one copy of the genome and are haploid Stem cells, which are diploid, can both replicate themselves and differentiate themselves for repair and replacement of specialized cells 3

Types of Cells Prokaryotic cells - Lack a nucleus Eukaryotic cells Must maintain basic functions for growth and reproduction, responding to environment, and utilizing energy. All cells can be divided into two main types Prokaryotic cells - Lack a nucleus Eukaryotic cells - Possess a nucleus and other organelles Figure 2.2 7

Domains of Life Biologists recognize three broad categories of organisms based on cellular complexity Archaea – extreme bacteria Eubacteria – more common forms of bacteria Eukarya – Includes both unicellular and multicellular eukaryotes; higher cells 8

The Archaea and Eubacteria are similar in that they are single-celled organisms, but they differ in certain features of their RNA and membranes. These cells lack nuclei and other organelles and therefore are categorized as prokaryotes. Eukaryotic cells are complex, with abundant and diverse organelles that compartmentalize biochemical reactions. Human cells are therefore eukaryotic.

Chemical Constituents Cells contain four types of macromolecules Type Examples Functions Carbohydrates Sugars, starches Energy, structure Lipids Fats, oils Membranes, hormones Proteins Myosin, collagen Enzymes, structure Nucleic Acids DNA, RNA Genetic information 10

Enzymes are proteins that catalyze the multitude of biochemical reactions that occur in the cell. The study of nucleic acids is key to the field of genetics.

An Animal Cell Surrounded by the plasma membrane Contains: - Cytoplasm - Organelles - Divide labor by partitioning certain areas or serving specific functions Figure 2.3

An Animal Cell Figure 2.3 Figure 2.3

The Nucleus The largest structure in a cell Surrounded by a double-layered nuclear envelope Contains: - Nuclear pores that allow movement of some molecules in and out - Nucleolus, which is the site of ribosome production - Chromosomes composed of DNA and proteins Figure 2.3

The Nucleus Figure 2.4 Figure 2.3 Figure 2.4

Secretion illustrates how organelles function together to coordinate the basic functions of life Secretion – The Eukaryotic Production Line Figure 2.5

Endoplasmic Reticulum (ER) Interconnected membranous tubules & sacs Winds from the nuclear envelope to the plasma membrane Rough ER contains ribosomes and is involved in protein synthesis Smooth ER does not contain ribosomes and is important in lipid synthesis Figure 2.3

Golgi Apparatus Stack of flat membrane-enclosed sacs Processing center that adds sugars forming glycoproteins and glycolipids Site of final protein folding Products are released into vesicles that bud off to the plasma membrane Figure 2.3

Lysosomes Membrane-bound sacs containing > 40 types of digestive enzymes Degrade bacteria, cellular debris, and nutrients Tay-Sachs is an inherited lysosomal storage disorder Figure 2.3 Figure 2.6

Peroxisomes Sacs with outer membranes studded with several types of enzymes that: Detoxify compounds from free radicals Break down lipids, rare biochemicals Synthesize bile acids Abundant in liver and kidney cells Figure 2.3

Mitochondria Surrounded by two membranes Site of ATP (energy) production “powerhouse of cell” Contain their own circular DNA Human mitochondrial DNA is inherited only from the mother Figure 2.7 Figure 2.3

Structures and Functions of Organelles Table 2.1

Plasma Membrane Forms a selective barrier A phospholipid bilayer - Phosphate end (hydrophilic) - Fatty acid chains (hydrophobic) Figure 2.8 Figure 2.3

Plasma Membrane Contains proteins, glycoproteins, and glycolipids - Important to cell function and interactions - May be receptors - Form channels for ions Figure 2.3 Figure 2.9

Faulty Ion Channels Cause Inherited Diseases Sodium channels - Mutations lead to absence or extreme pain Potassium channels - Mutations lead to impaired heart function and deafness Chloride channels - Mutations lead to cystic fibrosis “Burning man syndrome” channels become hypersensitive, in response to exercise, increase in room temperature or just putting on one’s socks. Salt trapped inside cells draws moisture and in thickens surrounding mucus. Figure 2.3

Cytoskeleton A meshwork of protein rods and tubules Figure 2.10 A meshwork of protein rods and tubules Includes three major types of proteins - Microtubules - Microfilaments - Intermediate filaments Figure 2.3

Cytoskeleton 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 and flagella Figure 2.3

Abnormalities Spherocytosis is a heredity defect in the cytoskeleton of the red blood cell. An abnormal cytoskeleton protein beneath the cell membrane and causes the red blood cells to balloon out, blocking narrow blood vessels in organs.

Cell Division and Death Normal growth and development require an intricate interplay between the rates of two processes Mitosis – Cell division - Produces two somatic cells from one Apoptosis – Cell death - Precise genetically-programmed sequence Figure 2.3

Figure 2.13 Figure 2.12

The Cell Cycle The sequence of events associated with cell division Figure 2.14 G phase: Gap for growth S phase: DNA synthesis M phase: Mitosis (nuclear division) Cytokinesis: Cell division Figure 2.3

Stages of the Cell Cycle Interphase - Prepares for cell division - Replicates DNA and subcellular structures - Composed of G1 – proteins, lipids, & carbs are produced S – DNA and proteins are made G2 – more proteins produced - Cells may exit the cell cycle at G1 or enter G0, a dormant phase Mitosis – Division of the nucleus Cytokinesis – Division of the cytoplasm Figure 2.3

Replication of Chromosomes Chromosomes are replicated during S phase prior to mitosis The result is two sister chromatids held together at the centromere Figure 2.15 Figure 2.3

Mitosis Used for growth, repair, and replacement Consists of a single division that produces two identical daughter cells A continuous process divided into 4 phases - Prophase - Metaphase - Anaphase - Telophase Figure 2.3

Mitosis in a Human Cell Figure 2.15 Figure 2.16

Prophase Replicated chromosomes condense Microtubules organize into a spindle Nuclear envelope and nucleolus break down Figure 2.3 Figure 2.16

Metaphase Chromosomes line up on the cell’s equator or metaphase plate Spindle microtubules are attached to centromeres of chromosomes Figure 2.3 Figure 2.16

Anaphase Centromeres divide Chromatids separate and become independent chromosomes - They move to opposite ends of the cell Figure 2.3 Figure 2.16

Telophase Cell pinches in middle Chromosomes uncoil Spindle disassembles Nuclear envelope reforms Figure 2.3 Figure 2.16

Cytokinesis Cytoplasmic division occurs after nuclear division is complete Organelles and macromolecules are distributed between the two daughter cells Microfilament band contracts, separating the two cells Figure 2.3

Mitosis Animation Figure 2.3

Cell Cycle Control Checkpoints ensure that mitotic events occur in the correct sequence Internal and external factors are involved Many types of cancer result from faulty checkpoints Figure 2.3

Cell Cycle Control Figure 2.17 Figure 2.16

Telomeres Located at the ends of the chromosomes Cellular clock limits number of divisions based on shrinking telomeres, after about 50 divisions Crowding, hormones, & growth factors are extracellular influences on mitosis Sperm, eggs, bone marrow, and cancer cells produce telomerase that prevent shortening of telomeres Why is this important? Figure 2.3

Apoptosis Begins when a cell receives a “death signal” Killer enzymes called caspases are activated -Destroy cellular components Phagocytes digest the remains Figure 2.3

Mitosis and apotosis work together to form functional body Programmed cell death is part of normal development Figure 2.19 Mitosis and apotosis work together to form functional body Cancer or other disorders can result from too much mitosis, too little apotosis Figure 2.18

Stem Cells A stem cell divides by mitosis - Produces daughter cells that retain the ability to divide and some that specialize Progenitor cells do not have the capacity of self-renewal Figure 2.3 Figure 2.22

Stem Cells All cells in the human body descend from stem cells via mitosis and differentiation Cells differentiate down cell lineages by differential gene expression Stem cells are present throughout life and provide growth and repair Figure 2.3

Figure 2.23 Figure 2.3

Stem Cells Stem cells and progenitor cells are described in terms of their developmental potential Totipotent – Can give rise to every cell type Pluripotent – Have fewer possible fates Multipotent – Have only a few fates Figure 2.3

Stem Cells in Health Care There are 3 general sources of human stem cells 1) Embryonic stem cells – Created in a lab dish using the inner cell mass (ICM) of an embryo 2) Induced pluripotent stem (iPS) cells – Somatic cells reprogrammed to differentiate into any of several cell types 3) Adult stem cells – Tissue-specific or somatic stem cells Figure 2.3

Stem Cells in Health Care Figure 2.24 Figure 2.24

Stem Cell Applications Stem cells are being used in four basic ways 1) Discovery and development of drugs 2) Observing the earliest sign of disease 3) Treatment of disease via implants and transplants 4) Stimulating stem cells in the body via the introduction of reprogramming proteins Figure 2.3

Stem Cell Applications Figure 2.25 Figure 2.3