Gromley Biochemistry, Cell and Molecular Biology, and Genetics

An Integrated Textbook
1. Auflage 2021
ISBN: 978-1-63853-478-5
Verlag: Thieme
Format: EPUB
Kopierschutz: 6 - ePub Watermark

E-Book, Englisch, 502 Seiten, ePub

by Zeynep Gromley and Adam Gromley is the first to cover molecular biology, cell biology, biochemistry (metabolism), and genetics in one comprehensive yet concise resource. Throughout the book, these topics are linked to other basic medical sciences, such as pharmacology, physiology, pathology, immunology, microbiology, and histology, for a truly integrated approach.

Key Highlights

• Easy-to-read text enhances understanding of underlying molecular mechanisms of disease
• Nearly 500 illustrations and tables help reinforce chapter learning objectives
• Textboxes throughout make connections with other preclinical disciplines
• End of unit high-order clinical vignette questions with succinct explanations help integrate basic science topics with clinical medicine

This textbook provides a robust review for medical students preparing for courses as well as exams. Dental, pharmacy, physician's assistant, nursing, and graduate students in pre-professional/bridge programs will also find this a beneficial learning tool.

This book includes complimentary access to a digital copy on https://medone.thieme.com.

Autoren/Hrsg.

Gromley, Zeynep

Gromley, Adam

Fachgebiete

• Naturwissenschaften Biowissenschaften Biochemie (nichtmedizinisch)
• Medizin | Veterinärmedizin Medizin | Public Health | Pharmazie | Zahnmedizin Vorklinische Medizin: Grundlagenfächer Molekulare Medizin, Zellbiologie
• Medizin | Veterinärmedizin Medizin | Public Health | Pharmazie | Zahnmedizin Vorklinische Medizin: Grundlagenfächer Biomechanik

Inhaltsverzeichnis

Part I
1. Anatomy of the Cell and Organelles
2. DNA Replication, Gene Mutations, and Repair
3. Transcription and Regulation of Transcription
4. Translation and Regulation of Translation
Part II
5. Cytoskeleton
6. Protein Sorting, Modifications, and Intracellular Traffic
7. Membrane Transport
8. Extracellular Matrix
9. Cell Adhesion and Membrane Junctions
10. Signal Transduction
11. Cell Cycle and Control of the Cell Cycle
12. Stem Cells and Hematopoiesis
13. Cell Injury, Apoptosis, and Necrosis
14. Hallmarks of Cancer and Cancer Biology
15. Molecular Principles of Cancer Treatments and Therapies
Part III
16. Enzymes and Enzyme Kinetics
17. Regulation of Enzyme Activity
18. Structure and Function of Proteins
19. Molecular and Biological Techniques
20. Plasma Proteins and the Diagnostic Use of Enzymes
Part IV
21. Digestion and Absorption of Carbohydrates
22. Glycolysis
23. Metabolism of Fructose, Galactose and the Pentose Phosphate Pathway (HMP Shunt)
24. Glycogen Metabolism and Regulation
25. Gluconeogenesis
26. Pyruvate Dehydrogenase and Tricarboxylic Acid (TCA) Cycle
27. Electron Transport Chain (ETC) and Oxidative Phosphorylation
28. Oxygen Toxicity and Antioxidants
29. Oxidation of Fatty Acids and Ketogenesis
30. Acid Base Chemistry and Acid Base Disorders
31. Glucose Homeostasis and Maintenance of Blood Glucose Concentrations
Part V
32. Digestion and Absorption of Proteins
33. Nitrogen Metabolism
34. Amino Acid Metabolism
35. Amino Acid Derivatives
36. Porphyrin Heme Metabolism and Iron Homeostasis
37. Nucleotide Metabolism
38. Vitamins in One-Carbon Metabolism
Part VI
39. Digestion and Absorption of Lipids
40. Synthesis of Fatty Acids and Triacylglycerols
41. Metabolism of Membrane Lipids and Lipid Derivatives
42. Cholesterol Metabolism
43. Blood Lipoproteins
44. Steroid Hormones and Vitamin D
45. Nutrition and Metabolism
46. Vitamins and Minerals
Part VII
47. DNA Packaging and Meiosis
48. Cytogenetics: Chromosomal Basis of Human Diseases
49. Single Gene Disorders: Autosomal Dominant and Recessive Inheritance
50. Sex-Linked and Non-Traditional Modes of Inheritance
51. Population Genetics
52. Genomic Imprinting and Epigenetics
53. Gene Interactions and Multifactorial Inheritance
54. Personalized Medicine
55. Developmental Genetics
56. Cancer Genetics

Leseproben

1 Anatomy of the Cell and Organelles

At the conclusion of this chapter, students will be able to:

• Identify the lipid, protein, and carbohydrate components of the plasma membrane

• Describe the basic functions of the plasma membrane, including selective permeability, cellular communication, and physical barrier functions

• Identify the major ions found inside the cell and in the extracellular environment as well as explain the variations of ion concentrations across cell membranes

• Identify the six major membrane-bound organelles of the human cell

• Describe the structure and major functions of each organelle

• Identify genetic diseases associated with dysfunction of the nuclear lamina, mitochondria, lysosomes, peroxisomes, and golgi apparatus and explain the molecular process affected in each

All living organisms are composed of building blocks called cells. These individual units consist of an aqueous solution enclosed by a lipid-rich membrane. Inside the cell exist all of the chemicals and molecules to sustain itself as well as those necessary to perform its requisite functions including cellular metabolism, chemical signaling, and, in some cases, the synthesis of products that will ultimately be expelled from the cell. In addition, the cell contains the machinery necessary to make an exact copy of itself, preserving the hereditary information that defines the individual organism.

Living organisms can be categorized into two main groups: eukaryotes, and prokaryotes (? Fig. 1.1a, b). The prokaryotes are unicellular organisms that can be further classified as eubacteria and archaebacteria. Prokaryotes typically possess a flagellum to allow for movement. In addition, they do not have membrane-bound organelles, nor do they have a nucleus. Instead, all of the genetic material is concentrated in an irregularly shaped region of the cytoplasm termed the nucleoid. The cell membrane of most prokaryotes is encased by a cell wall, which is itself surrounded by a cross-linked, mesh-like structure, called the peptidoglycan layer, which is composed of short amino acid chains linked to sugar molecules. The thickness of the peptidoglycan layer is used to distinguish between two main groups of bacteria: the gram positive and gram negative bacteria. Gram positive bacteria have a thick peptidoglycan layer and, hence, retain gram stain, whereas this layer in gram negative bacteria is thin and readily gives up the stain. Some classes of antibiotics work by inhibiting the synthesis of this peptidoglycan layer, which is essential for the bacteria’s survival. These include the beta lactam penicillin and the glycopeptide antibiotics vancomycin and bleomycin. (? Fig. 1.1)

In multicellular organisms, such as humans, organ systems are comprised of individual organs with specific functions. In turn, each organ is comprised of tissues with physiological roles tailored to that particular organ. These tissues are themselves made up of individual cells with specialized abilities that allow them to contribute to the overall function of the tissue. And so, cell function contributes to tissue function which contributes to organ function that ultimately leads to the proper functioning of the organ system. The importance of the individual cell cannot be overstated, as the ability of the organ system to function properly is determined by the health of the cells that make up the individual organs.

Fig. 1.1 (a) Anatomy of a typical prokaryotic cell. (b) Anatomy of (1) an animal cell and (2) a plant cell. (Source: Passarge E, ed. Color Atlas of Genetics. 4th Edition. New York, NY. Thieme; 2012.)

In humans, the body is made up of trillions of individual cells representing hundreds of different cells types. Despite this tremendous variation, nearly all vertebrate cells share the same general anatomy (? Fig. 1.2). Inside the cell are membrane-enclosed organelles such as the nucleus, mitochondria, lysosomes, peroxisomes, endoplasmic reticulum, and golgi apparatus. In addition to these organelles, the cells also contain a cytoskeleton that serves multiple functions in cellular integrity, cell motility, intracellular transport, and cellular division. Details of the cytoskeleton will be discussed in Chapter 5. All of these components are surrounded by a lipid-rich structure called the plasma membrane, which separates the inside of the cell from its exterior environment. (? Fig. 1.3)

1.1 The Plasma Membrane

The plasma membrane is formed from a lipid bilayer, serving as a selectively permeable barrier that controls the passage of ions and organic molecules into and out of the cell. This bilayer is asymmetric, having different components in the inner lipid layer versus the outer layer lipid layer. The layer facing the extracellular environment is known as the outer leaflet, and the layer facing the cytoplasm is termed the inner leaflet. This asymmetric structure is important for many cellular processes, as we will see later. The most abundant lipids within the plasma membrane are the phospholipids, which have a hydrophilic head connected to two hydrophobic tails via a glycerol backbone. The presence of both hydrophobic and hydrophilic parts means that these molecules are amphipathic, a characteristic that favors their formation into bilayers in an aqueous environment. There are four major phospholipids found in the plasma membrane. These are phosphotidylethanolamine, phosphatidylserine, phosphatidylcholine, and sphingomyelin. In addition to their role as a structural component of the plasma membrane, these phospholipids also serve as important mediators of other processes in the cell, including signal transduction and programmed cell death (Chapters 10 and 13). Another type of phospholipid, the phosphoinositides, are less abundant in the plasma membrane but perform important functions in transport vesicle targeting within the cell (Chapter 6) as well as cell signaling (Chapter 10). Besides phospholipids, the plasma membrane also contains cholesterol, glycolipids, and proteins (? Fig. 1.4a, b). Cholesterol represents approximately 20% of the lipid content by weight of the plasma membrane. The cholesterol molecule is short and rigid, allowing it to fill the spaces created by kinked unsaturated hydrocarbon rings of adjacent phospholipid molecules in the membrane. Like phospholipids, glycolipids are also amphipathic. However, these molecules differ from phospholipids in three fundamental ways: their hydrophilic head contains an oligosaccharide chain, the backbone is a sphingosine molecule instead of glycerol, and it lacks a phosphate group. The glycolipid molecules have important roles in cell recognition. For example, glycolipids are the antigenic determinant of the ABO blood groups. Nerve cell membranes have high concentrations of two specific kinds of glycolipids, the cerebrosides and the gangliosides. A defect in the normal turnover of these glycolipids is responsible for the devastating effects seen in individuals with lysosomal storage diseases, as we will see later in this chapter. (? Fig. 1.4a, b)

Fig. 1.2 (a) Comparison of prokaryotes and eukaryotes. (b) Components of a typical animal cell. (Source: Koolman J, Röhm K, ed. Color Atlas of Biochemistry. 3rd Edition. New York, NY. Thieme; 2012.)

Fig. 1.3 Classes of membrane-embedded proteins and complexes. (Source: Passarge E, ed. Color Atlas of Genetics. 4th Edition. New York, NY. Thieme; 2012.)

Membrane phospholipids are capable of moving and changing places with one another within the plane of the bilayer, a characteristic known as membrane fluidity. In contrast, they rarely exchange between the layers. When this does occur, it is mediated by specialized enzymes called flippases. This fluid nature of the plasma membrane is important for many of the cell’s functions. It enables membrane proteins to diffuse rapidly in the plane of the bilayer and to interact with one another, which is important for many aspects of cell signaling. It also permits membrane lipids and proteins to diffuse from sites where they are inserted into the bilayer after their synthesis to other regions of the cell. It ensures that membrane molecules are distributed evenly between daughter cells when a cell divides, and it allows membranes to fuse with one another and mix their molecules.

Two key factors determine the degree of fluidity of the membrane. The first is based on the length of the hydrocarbon tails of the phospholipids. Short hydrocarbon chains in adjacent lipid molecules have less tendency to form bonds with one another and, hence, allow for a more fluid membrane. In contrast, lipids with long chains would have more interactions with one another and would therefore decrease the fluidity. The second factor that determines the fluidity of the membrane is the amount of cholesterol. Since cholesterol packs within the spaces between adjacent phospholipid molecules, a higher percentage of cholesterol would create a more rigid, and therefore less fluid, membrane.

In addition to lipids and cholesterol, the plasma membrane is home to many different types of proteins (? Fig. 1.3). Some of these proteins are embedded in the plasma membrane and are called...