H. Lodish - Molecular Cell Biology (5ed, Freeman, 2003), страница 6

Recent advances in detectingdisease-causing mutations and in understanding how they affect cell functions offer exciting possibilities for reducingtheir often devastating effects.Sequencing of the human genome has shown that a verylarge proportion of our DNA does not code for any RNA orhave any discernible regulatory function, a quite unexpectedfinding.

Mutations in these regions usually produce no immediate effects—good or bad. However, such “indifferent”mutations in nonfunctional DNA may have been a majorplayer in evolution, leading to creation of new genes or newregulatory sequences for controlling already existing genes.For instance, since binding sites for transcription factors typically are only 10–12 nucleotides long, a few single-nucleotidemutations might convert a nonfunctional bit of DNA into afunctional protein-binding regulatory site.Much of the nonessential DNA in both eukaryotes andprokaryotes consists of highly repeated sequences that canmove from one place in the genome to another. These mobileDNA elements can jump (transpose) into genes, most commonly damaging but sometimes activating them.

Jumpinggenerally occurs rarely enough to avoid endangering the hostorganism. Mobile elements, which were discovered first inplants, are responsible for leaf color variegation and thediverse beautiful color patterns of Indian corn kernels. Byjumping in and out of genes that control pigmentation asplant development progresses, the mobile elements give riseto elaborate colored patterns. Mobile elements were laterfound in bacteria in which they often carry and, unfortunately, disseminate genes for antibiotic resistance.Now we understand that mobile elements have multiplied and slowly accumulated in genomes over evolutionary13time, becoming a universal property of genomes in presentday organisms. They account for an astounding 45 percentof the human genome. Some of our own mobile DNA elements are copies—often highly mutated and damaged—ofgenomes from viruses that spend part of their life cycle asDNA segments inserted into host-cell DNA.

Thus we carryin our chromosomes the genetic residues of infections acquired by our ancestors. Once viewed only as molecular parasites, mobile DNA elements are now thought to havecontributed significantly to the evolution of higher organisms (Chapter 10).1.3 The Work of CellsIn essence, any cell is simply a compartment with a wateryinterior that is separated from the external environment bya surface membrane (the plasma membrane) that preventsthe free flow of molecules in and out of cells. In addition, aswe’ve noted, eukaryotic cells have extensive internal membranes that further subdivide the cell into various compartments, the organelles.

The plasma membrane and othercellular membranes are composed primarily of two layers ofphospholipid molecules. These bipartite molecules have a“water-loving” (hydrophilic) end and a “water-hating” (hydrophobic) end. The two phospholipid layers of a membrane are oriented with all the hydrophilic ends directed toward the inner and outer surfaces and the hydrophobic endsburied within the interior (Figure 1-13). Smaller amounts ofCholesterolWater-seekinghead groupFatty chainsWater▲ FIGURE 1-13 The watery interior of cells is surroundedby the plasma membrane, a two-layered shell ofphospholipids. The phospholipid molecules are oriented withtheir fatty acyl chains (black squiggly lines) facing inward andtheir water-seeking head groups (white spheres) facing outward.Thus both sides of the membrane are lined by head groups,mainly charged phosphates, adjacent to the watery spaces insideand outside the cell. All biological membranes have the samebasic phospholipid bilayer structure.

Cholesterol (red) and variousproteins (not shown) are embedded in the bilayer. In actuality,the interior space is much larger relative to the volume of theplasma membrane depicted here.14CHAPTER 1 • Life Begins with Cellsother lipids, such as cholesterol, and many kinds of proteinsare inserted into the phospholipid framework.

The lipid molecules and some proteins can float sidewise in the plane ofthe membrane, giving membranes a fluid character. This fluidity allows cells to change shape and even move. However,the attachment of some membrane proteins to other molecules inside or outside the cell restricts their lateral movement. We learn more about membranes and how moleculescross them in Chapters 5 and 7.The cytosol and the internal spaces of organelles differfrom each other and from the cell exterior in terms of acidity,ionic composition, and protein contents. For example, thecomposition of salts inside the cell is often drastically different from what is outside. Because of these different “microclimates,” each cell compartment has its own assigned tasksin the overall work of the cell (Chapter 5).

The unique functions and micro-climates of the various cell compartmentsare due largely to the proteins that reside in their membranesor interior.We can think of the entire cell compartment as a factorydedicated to sustaining the well-being of the cell. Much cellular work is performed by molecular machines, somehoused in the cytosol and some in various organelles. Herewe quickly review the major tasks that cells carry out in theirpursuit of the good life.Cells Build and Degrade NumerousMolecules and StructuresOverview Animation: Biological Energy InterconversionsMEDIA CONNECTIONSAs chemical factories, cells produce an enormous number ofcomplex molecules from simple chemical building blocks. Allof this synthetic work is powered by chemical energy extracted primarily from sugars and fats or sunlight, in the caseof plant cells, and stored primarily in ATP, the universal“currency” of chemical energy (Figure 1-14).

In animal andplant cells, most ATP is produced by large molecular machines located in two organelles, mitochondria and chloroplasts. Similar machines for generating ATP are located inthe plasma membrane of bacterial cells. Both mitochondriaand chloroplasts are thought to have originated as bacteriathat took up residence inside eukaryotic cells and then became welcome collaborators (Chapter 8). Directly or indirectly, all of our food is created by plant cells using sunlightto build complex macromolecules during photosynthesis.Even underground oil supplies are derived from the decayof plant material.Cells need to break down worn-out or obsolete parts intosmall molecules that can be discarded or recycled.

Thishousekeeping task is assigned largely to lysosomes, organelles crammed with degradative enzymes. The interior oflysosomes has a pH of about 5.0, roughly 100 times moreacidic than that of the surrounding cytosol. This aids in thebreakdown of materials by lysosomal enzymes, which arespecially designed to function at such a low pH. To create thelow pH environment, proteins located in the lysosomal membrane pump hydrogen ions into the lysosome using energysupplied from ATP (Chapter 7). Lysosomes are assisted in thecell’s cleanup work by peroxisomes.

These small organellesare specialized for breaking down the lipid components ofmembranes and rendering various toxins harmless.Most of the structural and functional properties of cellsdepend on proteins. Thus for cells to work properly, the nu-Light (photosynthesis) orcompounds with highpotential energy (respiration)ADP + PiATPEnergySynthesis ofcellular macromolecules (DNA,RNA, proteins,polysaccharides)Synthesis of othercellular constituents(such as membranephospholipids andcertain requiredmetabolites)Cellular movements,including muscle contraction, crawling movements of entire cells,and movement ofchromosomes duringmitosis▲ FIGURE 1-14 ATP is the most common molecule usedby cells to capture and transfer energy.

ATP is formed fromADP and inorganic phosphate (Pi) by photosynthesis in plantsTransport ofmolecules againsta concentrationgradientGeneration of anelectric potentialacross a membrane(important for nervefunction)Heatand by the breakdown of sugars and fats in most cells. Theenergy released by the splitting (hydrolysis) of Pi from ATPdrives many cellular processes.1.3 • The Work of Cellsmerous proteins composing the various working compartments must be transported from where they are made totheir proper locations (Chapters 16 and 17).

Some proteinsare made on ribosomes that are free in the cytosol. Proteinssecreted from the cell and most membrane proteins, however,are made on ribosomes associated with the endoplasmicreticulum (ER). This organelle produces, processes, and shipsout both proteins and lipids. Protein chains produced on theER move to the Golgi apparatus, where they are furthermodified before being forwarded to their final destinations.Proteins that travel in this way contain short sequences ofamino acids or attached sugar chains (oligosaccharides) thatserve as addresses for directing them to their correct destinations.

These addresses work because they are recognizedand bound by other proteins that do the sorting and shippingin various cell compartments.Animal Cells Produce Their Own ExternalEnvironment and GluesThe simplest multicellular animals are single cells embeddedin a jelly of proteins and polysaccharides called the extracellular matrix. Cells themselves produce and secrete these materials, thus creating their own immediate environment(Chapter 6). Collagen, the single most abundant protein inthe animal kingdom, is a major component of the extracellular matrix in most tissues. In animals, the extracellular matrix cushions and lubricates cells. A specialized, especiallytough matrix, the basal lamina, forms a supporting layer underlying sheetlike cell layers and helps prevent the cells fromripping apart.The cells in animal tissues are “glued” together by celladhesion molecules (CAMs) embedded in their surfacemembranes.

Some CAMs bind cells to one another; othertypes bind cells to the extracellular matrix, forming a cohesive unit. The cells of higher plants contain relatively fewsuch molecules; instead, plants cells are rigidly tied togetherby extensive interlocking of the cell walls of neighboringIntermediate filamentscells. The cytosols of adjacent animal or plant cells often areconnected by functionally similar but structurally different“bridges” called gap junctions in animals and plasmodesmata in plants. These structures allow cells to exchange smallmolecules including nutrients and signals, facilitating coordinated functioning of the cells in a tissue.Cells Change Shape and MoveAlthough cells sometimes are spherical, they more commonlyhave more elaborate shapes due to their internal skeletonsand external attachments.