Plasma Membrane: Protection and Nutrient Acquisition
Biosynthetic Machinery: Endoplasmic Reticulum and Golgi Apparatus
Waste Disposal: Lysosomes and Proteasomes
Modular Signaling Proteins, Hubs, and
Components of the Extracellular Matrix
Proliferation and the Cell Cycle
Pathology literally translates to the study of suffering (Greek pathos = suffering, logos = study); as applied to modern medicine, it is the study of disease. Virchow was certainly correct in asserting that disease originates at the cellular level, but we now realize that cellular disturbances arise from alterations in molecules (genes, proteins, and others) that influence the survival and behavior of cells. Thus, the foundation of modern pathology is understanding the cellular and molecular abnormalities that give rise to diseases. It is helpful to consider these abnormalities in the context of normal cellular structure and function, which is the theme of this introductory chapter.
It is unrealistic (and even undesirable) to condense the vast and fascinating field of cell biology into a single chapter. Consequently, rather than attempting a comprehensive review, the goal here is to survey basic principles and highlight recent advances that are relevant to the mechanisms of disease that are emphasized throughout the rest of the book.
The sequencing of the human genome at the beginning of the 21st century represented a landmark achievement of biomedical science. Since then, the rapidly dropping cost of sequencing and the computational capacity to analyze vast amounts of data promise to revolutionize our understanding of health and disease. At the same time, the emerging information has also revealed a breathtaking level of complexity far beyond the linear sequencing of the genome. The potential for these new powerful tools to expand our understanding of pathogenesis and drive therapeutic innovation excites and inspires scientists and the lay public alike.
The human genome contains about 3.2 billion DNA base pairs. Yet, within the genome there are only roughly 20,000 protein-encoding genes, comprising just 1.5% of the genome. The proteins encoded by these genes are the fundamental constituents of cells, functioning as enzymes, structural elements, and signaling molecules. Although 20,000 underestimates the actual number of proteins encoded (many genes produce multiple RNA transcripts that encode distinct protein isoforms), it is nevertheless startling that worms composed of fewer than 1000 cells— and with genomes 30-fold smaller—are also assembled from roughly 20,000 protein-encoding genes. Perhaps even more unsettling is that many of these proteins are recognizable homologs of molecules expressed in humans. What then separates humans from worms?
The answer is not completely known, but evidence supports the assertion that the difference lies in the 98.5% of the human genome that does not encode proteins. The function of such long stretches of DNA (which has been called the “dark matter” of the genome) was mysterious for many years. However, it is now clear that more than 85% of the human genome is ultimately transcribed, with almost 80% being devoted to the regulation of gene expression. It follows that whereas proteins provide the building blocks http://ebooksmedicine.net
Euchromatin Nucleus (dense, inactive) (disperse, active)