Chapter 1 General Physiologic Processes lated with metabolic activity and rate of adenosine triphosphate(atp)pro- duction. The two mitochondrial membranes differ greatly in their properties 1. The inner bilayer has a much larger surface area because it forms cristae that project into the mitochondrial matrix. It contains the carnitine shuttle transporter for free fatty acids that can be beta oxidized to form acetyl-coenzyme a( Co-A)as substrate for the Krebs cycle It contains the transporters that function in association with the electron transport chain to pump hydrogen ions(H+)from the mitochondrial matrix into the space between the inner and outer mitochondrial membranes, thereby creating gradients for H charge(matrix =-150 mV), and free energy. The H* gradient is used, in part, for inner membrane co-transport of pyruvate and phosphate with H+ into the matrix. The charge gradient is used, art, for the accumulation of Ca++ into the matrix 2. The outer bilayer is more leaky to ions and small molecules than is th inner lay In addition to synthesizing ATP, mitochondria also synthesize urea and Mitochondria contain their own dna but also the dna codes for a lim ited number of proteins. Other proteins must be imported by active trans port from the cytosol of the cell. This requires close interaction between the inner and outer membranes Cytosol The cytosol is an aqueous solution of ions and proteins. It is contained by the plasma membrane and is stabilized by the cytoskeleton. In spite of very short intracellular diffusion distances, the activities of at least some ions Inner membrane Matrix Figure 1-3 Structure of a mitochondrion
lated with metabolic activity and rate of adenosine triphosphate (ATP) production. The two mitochondrial membranes differ greatly in their properties: 1. The inner bilayer has a much larger surface area because it forms cristae that project into the mitochondrial matrix. • It contains the carnitine shuttle transporter for free fatty acids that can be beta oxidized to form acetyl-coenzyme A (Co-A) as substrate for the Krebs cycle. • It contains the transporters that function in association with the electron transport chain to pump hydrogen ions (H+) from the mitochondrial matrix into the space between the inner and outer mitochondrial membranes, thereby creating gradients for H+, charge (matrix = –150 mV), and free energy. The H+ gradient is used, in part, for inner membrane co-transport of pyruvate and phosphate with H+ into the matrix. The charge gradient is used, in part, for the accumulation of Ca++ into the matrix. 2. The outer bilayer is more leaky to ions and small molecules than is the inner layer. In addition to synthesizing ATP, mitochondria also synthesize urea and heme. Mitochondria contain their own DNA but also the DNA codes for a limited number of proteins. Other proteins must be imported by active transport from the cytosol of the cell. This requires close interaction between the inner and outer membranes. Cytosol The cytosol is an aqueous solution of ions and proteins. It is contained by the plasma membrane and is stabilized by the cytoskeleton. In spite of very short intracellular diffusion distances, the activities of at least some ions Chapter 1 General Physiologic Processes 5 Outer membrane Inner membrane Cristae Matrix Figure 1–3 Structure of a mitochondrion
PDQ PHYSIOLOGY may not be homogeneous throughout the cytosol, and the importance of this for normal function is not yet fully evident. Cytoskeleton The cytoskeleton, an arrangement of intracellular structural elements, (1) helps maintain cell shape, (2) permits motion of one part of a cell relative to other parts, and(3) provides the machinery for the locomotion of the whole cell. the skeletal elements are, in descending order of size, microtubules, intermediate filaments, and actin (or microfilaments Microtubules, centrioles, and ciliae. Microtubules are hollow, cylindrical arrangements of the proteins a- and B-tubulin, 20 to 30 nm in diameter and 10 to 25 um in length. They grow from one end(the plus end)by polymerization of tubulin, whereas the minus end tends to disintegrate by hydrolysis unless it is stabilized. Microtubules are present in almost all mammalian cells and have three main functions: (1)control of the mitotic process,(2)movements of ciliae and flagellae, and (3)guided intracellular transport of proteins or vesicles. Control of the mitotic process. In most cells, with the notable exception of nerve cells, the negative end of most microtubules is anchored and sta- bilized in the centrosome. The plus ends, as long as they are free, grow from the pericentriolar material of the centrosome along an arbitrary path During the S phase of the cell replication cycle, when DNA replicates, the centrosome duplicates and divides into two equal parts, each containing a centriole pair. When mitosis begins, the two centrosomes move to opposite sides of the nucleus and form the two poles of the mitotic spindle, an array of microtubules that aligns chromosomes and holds them in place for the subsequent steps of cell division. These aspects are described more fully below(see The Cell Cycle) In the long phase preceding mitosis, the configuration of microtubules attached to a centrosome changes continually as new microtubules grow by tubulin polymerization at the plus end and old ones disintegrate by tubu lin hydrolysis at the minus end. A variety of chemical agents can inhibit microtubule formation and, with that, inhibit cell division. Examples of such chemical agents, all of which bind a-and B-tubulin, are colchicin, vin- blastin, and vincristine. n that lies near the nucleus. The centrosome contains amorphous pericentriolar and two centrioles(see Figure 1-4), each a pair of cylindrical bodies, positioned
may not be homogeneous throughout the cytosol, and the importance of this for normal function is not yet fully evident. Cytoskeleton The cytoskeleton, an arrangement of intracellular structural elements, (1) helps maintain cell shape, (2) permits motion of one part of a cell relative to other parts, and (3) provides the machinery for the locomotion of the whole cell. The primary skeletal elements are, in descending order of size, microtubules, intermediate filaments, and actin (or microfilaments). Microtubules, centrioles, and ciliae. Microtubules are hollow, cylindrical arrangements of the proteins α- and β-tubulin, 20 to 30 nm in diameter and 10 to 25 µm in length. They grow from one end (the plus end) by polymerization of tubulin, whereas the minus end tends to disintegrate by hydrolysis unless it is stabilized. Microtubules are present in almost all mammalian cells and have three main functions: (1) control of the mitotic process, (2) movements of ciliae and flagellae, and (3) guided intracellular transport of proteins or vesicles. Control of the mitotic process. In most cells, with the notable exception of nerve cells, the negative end of most microtubules is anchored and stabilized in the centrosome.* The plus ends, as long as they are free, grow from the pericentriolar material of the centrosome along an arbitrary path. During the S phase of the cell replication cycle, when DNA replicates, the centrosome duplicates and divides into two equal parts, each containing a centriole pair. When mitosis begins, the two centrosomes move to opposite sides of the nucleus and form the two poles of the mitotic spindle, an array of microtubules that aligns chromosomes and holds them in place for the subsequent steps of cell division. These aspects are described more fully below (see The Cell Cycle). In the long phase preceding mitosis, the configuration of microtubules attached to a centrosome changes continually as new microtubules grow by tubulin polymerization at the plus end and old ones disintegrate by tubulin hydrolysis at the minus end. A variety of chemical agents can inhibit microtubule formation and, with that, inhibit cell division. Examples of such chemical agents, all of which bind α- and β-tubulin, are colchicin, vinblastine, and vincristine. 6 PDQ PHYSIOLOGY *A region that lies near the nucleus. The centrosome contains amorphous pericentriolar material and two centrioles (see Figure 1–4), each a pair of cylindrical bodies, positioned at right angles to each other
Chapter 1 General Physiologic Processes Movements of ciliae and flagellae. Ciliae and flagellae are hair-like cell sur face projections. Their walls are formed by nine arrays of paired tubula structures,much in the same way as centrioles are formed by nine arrays of triplets(Figure 1-4). They grow from and are anchored to structures called basal bodies, whose structure resembles that of each member of a centriole pair. A motor protein, dynein, causes the bending and sweeping motion of these projections. The heads of this molecule project from one tubular struc ture of a pair to the other fiber, bind there, hydrolyze ATP, and use the ated energy to walk"along the fiber, thereby causing local bending Intracellular transport. Microtubules serve as binding sites for motor proteins that are able to hydrolyze ATP and use the liberated energy to cause motion and perform mechanical work. The kinesins move and can carry cargo toward the positive end of the microtubule The dyneins move and carry cargo in the opposite direction, toward the negative end of the microtubule Intermediate filaments. These elements of the cytoskeleton are 12 to 15 nm in diameter and include a variety of polymerized, mechanically stiff polypeptides, such as keratin, desmin, vimentin, lamin, and others. The relative abundance of different filamentous proteins varies among different cells: Keratin is found in epithelial cells, hair, and nails Desmin filaments link together the myofibrils in striated muscle cells Vimentin is found mostly in fibroblasts The lamins are the major constituent of the intermediate filament mesh that lines the inner surface of the nuclear membrane( the nuclear lamina) Figure 1-4 Schematic of a centriole. Nine groups of three microtubules run longitudinally in le walls of each centriole
Movements of ciliae and flagellae. Ciliae and flagellae are hair-like cell surface projections. Their walls are formed by nine arrays of paired tubular structures, much in the same way as centrioles are formed by nine arrays of triplets (Figure 1–4). They grow from and are anchored to structures called basal bodies, whose structure resembles that of each member of a centriole pair. A motor protein, dynein, causes the bending and sweeping motion of these projections. The heads of this molecule project from one tubular structure of a pair to the other fiber, bind there, hydrolyze ATP, and use the liberated energy to “walk” along the fiber, thereby causing local bending. Intracellular transport. Microtubules serve as binding sites for motor proteins that are able to hydrolyze ATP and use the liberated energy to cause motion and perform mechanical work. • The kinesins move and can carry cargo toward the positive end of the microtubule. • The dyneins move and carry cargo in the opposite direction, toward the negative end of the microtubule. Intermediate filaments. These elements of the cytoskeleton are 12 to 15 nm in diameter and include a variety of polymerized, mechanically stiff polypeptides, such as keratin, desmin, vimentin, lamin, and others. The relative abundance of different filamentous proteins varies among different cells: • Keratin is found in epithelial cells, hair, and nails. • Desmin filaments link together the myofibrils in striated muscle cells. • Vimentin is found mostly in fibroblasts. • The lamins are the major constituent of the intermediate filament mesh that lines the inner surface of the nuclear membrane (the nuclear lamina). Chapter 1 General Physiologic Processes 7 Figure 1–4 Schematic of a centriole. Nine groups of three microtubules run longitudinally in the walls of each centriole
DQ PHYSIOLOGY Ankyrin and spectrin fix in place the 3Na*/2K+ pump that is found in all cell membranes Intermediate filaments are thought to give structural strength to cells and help them withstand mechanical stress. Actin filaments. Actin is an abundant cytosolic protein. It exists in F- actin, the polymerized, fibrous form, as a helical arrangement of monomeric G-actin chains. They are present throughout the cell and are concentrated in a narrow band just under the plasma membrane. A variety of proteins form anchoring links between this band and the elements of the plasma membrane. Actin has many additional functions in cells, including(1) aggregation into bundles so as to form microfilaments and (2)participation in movements of the cell surface, including phagocytosis Plasma membrane The plasma membrane defines the perimeter of the cell. Its special compo- Q b port/import functions of substances that were synthesized or are to metabolized within the cell control of intracellular composition, 3. recognition of other cells, and 4. interaction with neighboring cell Membrane structure The two major components are lipids and proteins in prop that among different tissues. The lipids can both rotate and move laterally within their membrane leaf, the proteins are relatively fixed in position because of cytoskeletal (Table 1-1) Lipids. More than half the lipid mass in plasma membranes is phospholipids and their physicochemical behavior imparts many of the characteristics that are associated with cell membranes. The plasma membrane also contains a high proportion of cholesterol. There are two classes of phospholipids: glycero-phospholipids and sphingolipids. Both contain a phosphorylated, charged head group and a pair of different noncharged hydrocarbon tails(Figure 1-5) In an aqueous medium, phospholipids arrange themselves in a double layer with the fatty acid tails facing one another so that the charged heads
• Ankyrin and spectrin fix in place the 3Na+/2K+ pump that is found in all cell membranes. Intermediate filaments are thought to give structural strength to cells and help them withstand mechanical stress. Actin filaments. Actin is an abundant cytosolic protein. It exists in Factin, the polymerized, fibrous form, as a helical arrangement of monomeric G-actin chains. They are present throughout the cell and are concentrated in a narrow band just under the plasma membrane. A variety of proteins form anchoring links between this band and the elements of the plasma membrane. Actin has many additional functions in cells, including (1) aggregation into bundles so as to form microfilaments and (2) participation in movements of the cell surface, including phagocytosis. Plasma Membrane The plasma membrane defines the perimeter of the cell. Its special composition allows 1. export/import functions of substances that were synthesized or are to be metabolized within the cell, 2. control of intracellular composition, 3. recognition of other cells, and 4. interaction with neighboring cells. Membrane Structure The two major components are lipids and proteins in proportions that vary among different tissues. The lipids can both rotate and move laterally within their membrane leaf; the proteins are relatively fixed in position because of cytoskeletal anchoring (Table 1–1). Lipids. More than half the lipid mass in plasma membranes is phospholipids and their physicochemical behavior imparts many of the characteristics that are associated with cell membranes. The plasma membrane also contains a high proportion of cholesterol. There are two classes of phospholipids: glycero-phospholipids and sphingolipids. Both contain a phosphorylated, charged head group and a pair of different, noncharged hydrocarbon tails (Figure 1–5). In an aqueous medium, phospholipids arrange themselves in a double layer with the fatty acid tails facing one another so that the charged heads 8 PDQ PHYSIOLOGY
Chapter 1 General Physiologic Processes face the watery medium. This arrangement results from the fact that water is a charged molecule. ' The compositions of the two halves of the bilayer forming the plasma membrane are different. For example, the outer half contains most of the glycolipids(lipids with sugar groups attached to them). These are particu- larly suited for membrane protection, cell-to-cell recognition, Ca** binding, electrical insulation, and interactions with the extracellular matrix. Glycero-phospholipids. In the glycero-phospholipids, the two hydro- carbon tails are fatty acids that are joined at one end by glycerol. This gen eral structure is called diacylglycerol(DAG)(see Figure 1-5). A phosphate group links a charge-carrying head to the daG One of the tails may be kinked or straight, depending on whether ther is a cis double bond between one or more of the carbon pairs. Each cis de ble bond bestows a small kink. If the tails are straight, then the molecule assumes a conical shape; an aggregation of them will form a sphere, such as a lysosome. If, however, one tail is kinked, then the molecule is cylindrical in outline, and several of them will aggregate to form a flat layer. The plasma membrane contains a significant number of kinked-tail phospholipids Both hydrogen(H)atoms in water(H2O) gen atom carries a partial negative charge positive charge, whereas t water molecules interact nother because the positively charged hy h to the negatively charged oxygen(O)on th Table 1-1 Components of the Plasma Membrane Component Classes Subclasses Function Glycero- Two fatty acid tails joined by Phospholipids Phospholipids a glycerol-containing head LIPIDS Sphingolipids Head joins 1 fatty acid tail to Cholesterol Steroid ring contributes rigidity to membrane Peripheral Proteins Enzymes or signal transducers PROTEINS Integral Proteins Channel Proteins Selective ion channels Carrier Proteins Selective transporters CARBO- Extracellular coating HYDRATES glycocalyx]
face the watery medium. This arrangement results from the fact that water is a charged molecule.* The compositions of the two halves of the bilayer forming the plasma membrane are different. For example, the outer half contains most of the glycolipids (lipids with sugar groups attached to them). These are particularly suited for membrane protection, cell-to-cell recognition, Ca++ binding, electrical insulation, and interactions with the extracellular matrix. Glycero-phospholipids. In the glycero-phospholipids, the two hydrocarbon tails are fatty acids that are joined at one end by glycerol. This general structure is called diacylglycerol (DAG) (see Figure 1–5). A phosphate group links a charge-carrying head to the DAG. One of the tails may be kinked or straight, depending on whether there is a cis double bond between one or more of the carbon pairs. Each cis double bond bestows a small kink. If the tails are straight, then the molecule assumes a conical shape; an aggregation of them will form a sphere, such as a lysosome. If, however, one tail is kinked, then the molecule is cylindrical in outline, and several of them will aggregate to form a flat layer. The plasma membrane contains a significant number of kinked-tail phospholipids. Chapter 1 General Physiologic Processes 9 *Both hydrogen (H) atoms in water (H2O) carry a partial positive charge, whereas the oxygen atom carries a partial negative charge. As a result, water molecules interact with one another because the positively charged hydrogen atoms (H) on one molecule are attracted to the negatively charged oxygen (O) on the another. Table 1–1 Components of the Plasma Membrane Component Classes Subclasses Function Glycero- Two fatty acid tails joined by Phospholipids Phospholipids a glycerol-containing head LIPIDS Sphingolipids Head joins 1 fatty acid tail to sphingosine Cholesterol Steroid ring contributes rigidity to membrane Peripheral Proteins Enzymes or signal transducers PROTEINS Integral Proteins Channel Proteins Selective ion channels Carrier Proteins Selective transporters CARBO- Extracellular coating HYDRATES (glycocalyx)