Chapter 1: Functional Organization of the Human Body PDF

CHAPTER 1 Functional Organization of the Human Body and Control of the “Internal Environment” Physiology is the science that seeks to understand the function of living organisms and their parts. In human phys...

CHAPTER 1 Functional Organization of the Human Body and Control of the “Internal Environment” Physiology is the science that seeks to understand the function of living organisms and their parts. In human physiology, we are concerned with the characteristics of the human body that allow us to sense our environment, move about, think and communicate, reproduce, and perform all of the functions that enable us to survive and thrive as living beings. Human physiology is a broad subject that attempts to explain the specific characteristics and mecha- nisms of the human body that make it a living being. The subject includes the functions of molecules and subcellular components; tissues; organs; organ sys- tems, such as the cardiovascular system; and the interaction and communication among these compo- nents. A distinguishing feature of physiology is that it seeks to integrate the functions of all of the parts of the body to understand the function of the entire human body. Life in the human being relies on this total function, which is considerably more complex than the sum of the functions of the individual cells, tissues, and organs. ois an Cells Are the Living Units of the Body. Each organ aggregate of many cells held together by intercellular supporting structures. The entire body contains about 100 trillion cells, each of which is adapted to perform special functions. These individual cell functions are coordinated by multiple regulatory systems operating in cells, tissues, organs, and organ systems. Although the many cells of the body differ from each other in their special functions, all of them have certain basic characteristics. For example, (1) oxygen combines with breakdown products of fat, carbohy- drates, or protein to release energy that is required for function of the cells; (2) most cells have the abil- ity to reproduce, and whenever cells are destroyed, the remaining cells often regenerate new cells until the appropriate number is restored; and (3) cells are bathed in extracellular fluid, the constituents of which are precisely controlled. 3 4 UNIT I Introduction to Physiology: The Cell and General Physiology MECHANISMS OF HOMEOSTASIS— MAINTENANCE OF NEARLY CONSTANT INTERNAL ENVIRONMENT (p. 4) Essentially all the organs and tissues of the body per- form functions that help maintain the constituents of the extracellular fluid so they are relatively stable, a condition called homeostasis. Much of our discussion of physiology focuses on mechanisms by which the cells, tissues, and organs contribute to homeostasis. Extracellular Fluid Transport and Mixing System—The Blood Circulatory System Extracellular fluid is transported throughout the body in two stages. The first stage is movement of blood throughout the circulatory system, and the second stage is movement of fluid between the blood capil- laries and cells. The circulatory system keeps the flu- ids of the internal environment continuously mixed by pumping blood through the vascular system. As blood passes through the capillaries, a large portion of its fluid diffuses back and forth into the intersti- tial fluid that lies between the cells, allowing continu- ous exchange of substances between the cells and the interstitial fluid and between the interstitial fluid and the blood. Origin of Nutrients in the Extracellular Fluid The respiratory system provides oxygen for the body and removes carbon dioxide. The gastrointestinal system digests food and facili- tates absorption of various nutrients, including car- bohydrates, fatty acids, and amino acids, into the extracellular fluid. The liver changes the chemical composition of many of the absorbed substances to more us- able forms, and other tissues of the body (e.g., fat cells, kidneys, endocrine glands) help modify the absorbed substances or store them until they are needed. The musculoskeletal system consists of skeletal mus- cles, bones, tendons, joints, cartilage, and ligaments. Without this system, the body could not move to the appropriate place to obtain the foods required for nutrition. This system also protects internal organs and supports the body.  Functional Organization of the Human Body and Control of the 5 “Internal Environment” Removal of Metabolic End Products (p. 5) The respiratory system not only provides oxygen to the extracellular fluid but also removes carbon diox- ide, which is produced by the cells, released from the blood into the alveoli, and then released to the exter- nal environment. The kidneys excrete most of the waste products other than carbon dioxide. The kidneys play a ma- jor role in regulating extracellular fluid composition by controlling excretion of salts, water, and waste products of the chemical reactions of the cells. By controlling body fluid volumes and compositions, the kidneys also regulate blood volume and blood pressure. The liver eliminates certain waste products pro- duced in the body, as well as toxic substances that are ingested. Regulation of Body Functions The nervous system directs the activity of the muscular system, thereby providing locomotion. It also controls the function of many internal or- gans through the autonomic nervous system, and it allows us to sense our external and internal en- vironment and to be intelligent beings so we can obtain the most advantageous conditions for sur- vival. The hormone systems control many metabolic func- tions of the cells, such as growth, rate of metabolism, and special activities associated with reproduction. Hormones are secreted into the bloodstream and are carried to tissues throughout the body to help regu- late cell function. Protection of the Body The immune system provides the body with a defense mechanism that protects against foreign invaders, such as bacteria and viruses, to which the body is exposed daily. The integumentary system, which is composed mainly of skin, provides protection against injury and defense against foreign invaders, as well as protection of underlying tissues against dehydra- tion. The skin also serves to regulate body temper- ature. 6 UNIT I Introduction to Physiology: The Cell and General Physiology Reproduction The reproductive system provides for formation of new beings like ourselves. Even this function can be consid- ered a homeostatic function because it generates new bodies in which trillions of additional cells can exist in a well-regulated internal environment. CONTROL SYSTEMS OF THE BODY (p. 6) The human body has thousands of control systems that are essential for homeostasis. For example, genetic systems operate in all cells to control intracellular and extracellular functions. Other control systems operate within the organs or throughout the entire body to con- trol interactions among the organs. Regulation of oxygen and carbon dioxide concentra- tions in the extracellular fluid is a good example of multi- ple control systems that operate together. In this instance, the respiratory system operates in association with the nervous system. When carbon dioxide concentration in the blood increases above normal, the respiratory center is excited, causing the person to breathe rapidly and deeply. This breathing increases the expiration of carbon dioxide and therefore removes it from the blood and the extracel- lular fluid until the concentration returns to normal. Normal Ranges of Important Extracellular Fluid Constituents Table 1–1 shows some important constituents of extra- cellular fluid along with their normal values, normal ranges, and maximum limits that can be endured for short periods without the occurrence of death. Note the narrowness of the ranges; levels outside these ranges are usually the cause or the result of illnesses. Characteristics of Control Systems Most Control Systems of the Body Operate by Negative Feedback. For regulation of carbon dioxide concentration, as discussed, a high concentration of carbon dioxide in the extracellular fluid increases pulmonary ventilation, which decreases carbon dioxide concentration, moving it toward normal levels. This mechanism is an example of negative feedback; that is, any stimulus that attempts to change the carbon dioxide concentration is counteracted by a response that is negative to the initiating stimulus.  Functional Organization of the Human Body and Control of the 7 “Internal Environment” Table 1–1 Some Important Constituents and Physical Characteristics of the Extracellular Fluid, Normal Range of Control, and Approximate Nonlethal Limits for Short Periods Average Approximate Normal Normal Nonlethal Parameter Units Values Ranges Limits Oxygen (venous) mm Hg 40 35–45 10–1000 Carbon dioxide mm Hg 45 40–50 5–80 (venous) Sodium ion mmol/L 142 138–146 115–175 Potassium ion mmol/L 4.2 3.8–5.0 1.5–9.0 Calcium ion mmol/L 1.2 1.0–1.4 0.5–2.0 Chloride ion mmol/L 106 103–112 70–130 Bicarbonate ion mmol/L 24 22–29 8–45 Glucose mg/dL 90 75–95 20–1500 Body temperature °F (°C) 98.4 98–98.8 65–110 (37.0) (37.0) (18.3–43.3) Acid-base pH 7.4 7.3–7.5 6.9–8.0 The degree of effectiveness with which a control system maintains constant conditions is determined by the gain of the negative feedback. The gain is calculated according to the following formula: Gain = Correction/Error Some control systems, such as those that regulate body temperature, have feedback gains as high as −33, which simply means that the degree of correction is 33 times greater than the remaining error. Feed-Forward Control Systems Anticipate Changes. Because of the many interconnections between control systems, the total control of a particular body function may be more complex than can be accounted for by simple negative feedback. For example, some movements of the body occur so rapidly that there is not sufficient time for nerve signals to travel from some of the peripheral body parts to the brain and then back to the periphery in time to control the movements. Therefore, the brain uses feed-forward control to cause the required muscle contractions. Sensory nerve signals from the moving parts inform the brain in retrospect of whether the appropriate movement, as envisaged by 8 UNIT I Introduction to Physiology: The Cell and General Physiology the brain, has been performed correctly. If it has not, the brain corrects the feed-forward signals it sends to the muscles the next time the movement is required. This process is also called adaptive control, which is, in a sense, delayed negative feedback. Positive Feedback Can Sometimes Cause Vicious Cycles and Death, and Other Times It Can Be Useful. A system that exhibits positive feedback responds to a perturbation with changes that amplify the perturbation and therefore leads to instability rather than stability. For example, severe hemorrhage may lower blood pressure to such a low level that blood flow to the heart is insufficient to maintain normal cardiac pumping; as a result, blood pressure falls even lower, further diminishing blood flow to the heart and causing still more weakness of the heart. Each cycle of this feedback leads to more of the same, which is a positive feedback or a vicious cycle. In some cases the body uses positive feedback to its advantage. An example is the generation of nerve sig- nals. When the nerve fiber membrane is stimulated, the slight leakage of sodium ions into the cell causes open- ing of more channels, more sodium entry, more change in membrane potential, and so forth. Therefore, a slight leak of sodium into the cell becomes an explosion of sodium entering the interior of the nerve fiber, which creates the nerve action potential. SUMMARY—AUTOMATICITY OF THE BODY (p. 10) The body is a social order of about 100 trillion cells orga- nized into various functional structures, the largest of which are called organs. Each functional structure, or organ, helps maintain a constant internal environ- ment. As long as homeostasis is maintained, the cells of the body continue to live and function properly. Thus, each cell benefits from homeostasis and, in turn, each cell contributes its share toward maintenance of homeostasis. This reciprocal interplay provides con- tinuous automaticity of the body until one or more functional systems lose their ability to contribute their share of function. When this loss happens, all the cells of the body suffer. Extreme dysfunction leads to death, whereas moderate dysfunction leads to sickness.  CHAPTER 2 The Cell and Its Functions ORGANIZATION OF THE CELL (p. 11) Figure 2–1 shows a typical cell, including the nucleus and cytoplasm, which are separated by the nuclear membrane. The cytoplasm is separated from interstitial fluid by a cell membrane that surrounds the cell. The substances that make up the cell are collectively called protoplasm, which is composed mainly of the following: Water constitutes 70 percent to 85 percent of most cells. Ions/electrolytes provide inorganic chemicals for cel- lular reactions. Some of the most important ions in the cell are potassium, magnesium, phosphate, sul- fate, bicarbonate, and small quantities of sodium, chloride, and calcium. Proteins normally constitute 10 to 20 percent of the cell mass. They can be divided into two types: struc- tural proteins and globular (functional) proteins, which are mainly enzymes. Lipids constitute about 2 percent of the total cell mass. Among the most important lipids in the cells are phospholipids, cholesterol, triglycerides, and neu- tral fats. In adipocytes (fat cells), triglycerides ac- count for as much as 95 percent of the cell mass and represent the body’s main energy storehouse. Carbohydrates play a major role in nutrition of the cell. Most human cells do not store large amounts of carbohydrates, which usually average about 1 percent of the total cell mass but may be as high as 3 percent in muscle cells and 6 percent in liver cells. The small amount of carbohydrates in the cells is usually stored in the form of glycogen, an insoluble polymer of glucose. PHYSICAL STRUCTURE OF THE CELL (p. 12) The cell (Figure 2–1) is not merely a bag of fluid and chemicals; it also contains highly organized physi- cal structures called organelles. Some of the principal organelles of the cell are the cell membrane, nuclear membrane, endoplasmic reticulum (ER), Golgi appara- tus, mitochondria, lysosomes, and centrioles. The Cell and Its Organelles Are Surrounded by Membranes Composed of Lipids and Proteins. The membranes that surround the cell and its organelles 9 10 UNIT I Introduction to Physiology: The Cell and General Physiology Chromosomes and DNA Centrioles Secretory granule Golgi apparatus Microtubules Nuclear Cell membrane membrane Cytoplasm Nucleolus Glycogen Ribosomes Lysosome Mitochondrion Granular Smooth Microfilaments endoplasmic (agranular) reticulum endoplasmic reticulum Figure 2–1 Reconstruction of a typical cell, showing the internal or- ganelles in the cytoplasm and nucleus. include the cell membrane, nuclear membrane, and membranes of the ER, mitochondria, lysosomes, and Golgi apparatus. They provide barriers that prevent free movement of water and water-soluble substances from one cell compartment to another. Proteins in the membrane often penetrate the membrane, providing pathways (channels) to allow movement of specific substances through the membranes. The Cell Membrane Is a Lipid Bilayer With Inserted Proteins. The lipid bilayer is composed almost entirely of phospholipids, sphingolipids, and cholesterol. Phos- pholipids are the most abundant of the cell lipids and have a water-soluble (hydrophilic) portion and a portion that is soluble only in fats (hydrophobic). The hydrophobic portions of the phospholipids face each other, whereas the hydrophilic parts face the two surfaces of the membrane in contact with the surrounding interstitial fluid and the cell cytoplasm. This lipid bilayer membrane is highly permeable to lipid-soluble substances, such as oxygen, carbon diox- ide, and alcohol, but it acts as a major barrier to water- soluble substances, such as ions and glucose. Floating in the lipid bilayer are proteins, most of which are glyco- proteins (proteins combined with carbohydrates).  The Cell and Its Functions 11 There are two types of membrane protein: the inte- gral proteins, which protrude through the membrane, and the peripheral proteins, which are attached to the inner surface of the membrane and do not penetrate. - Many of the integral proteins provide structural chan- nels (pores) through which water-soluble substances, especially ions, can diffuse. Other integral proteins act as carrier proteins for the transport of substances, -> sometimes against their gradients for diffusion. -> Integral proteins can also serve as receptors for sub- stances, such as peptide hormones, that do not easily penetrate the cell membrane. The peripheral proteins are normally attached to one > of the integral proteins and usually function as enzymes that catalyze chemical reactions of the cell. The membrane carbohydrates occur mainly in com- bination with proteins and lipids in the form of glyco- proteins and glycolipids. The “glyco” portions of these molecules usually protrude to the outside of the cell. Many other carbohydrate compounds, called proteogly- cans, which are mainly carbohydrate substances bound 2 together by small protein cores, are loosely attached to the outer surface; thus, the entire outer surface of the cell often has a loose carbohydrate coat called the glycocalyx. The carbohydrates on the outer surface of the cell have multiple functions: (1) they are often negatively charged and therefore repel other molecules that are negatively charged; (2) the glycocalyx of cells may attach to other cells (thus the cells attach to each other); (3) some of the carbohydrates act as receptors for binding hormones; and (4) some carbohydrate moieties enter into immune reactions, as discussed in Chapter 35. The Endoplasmic Reticulum Synthesizes Multiple Substances in the Cell. A large network of tubules and vesicles, called the endoplasmic reticulum (ER), penetrates almost all parts of the cytoplasm. The ER membrane provides an extensive surface area for the manufacture of many substances used inside the cells + and released from some cells. They include proteins, carbohydrates, lipids, and other structures such as lysosomes, peroxisomes, and secretory granules. Lipids are made within the ER wall. For the synthesis of proteins, ribosomes attach to the outer surface of the granular ER. These ribosomes function in association with messenger RNA to synthesize many proteins that then enter the Golgi apparatus, where the molecules are further modified before they are released or used in the cell. Part of the ER has ② no attached ribosomes and is called the agranular, or smooth, ER. The agranular ER 12 UNIT I Introduction to Physiology: The Cell and General Physiology functions for the synthesis of lipid substances and for other processes of the cells promoted by intrareticular enzymes. The Golgi Apparatus Functions in Association With the ER. The Golgi apparatus has membranes similar to those of the agranular ER, is prominent in secretory cells, and is located on the side of the cell from which the secretory substances are extruded. Small transport vesicles, also called ER vesicles, continually pinch off from theo ER and-> then fuse with the Golgi apparatus. In this way, substances entrapped in the ER vesicles are transported from the ER to the Golgi apparatus. The substances are then-i processed=in the Golgi apparatus to form lysosomes, secretory vesicles, and other cytoplasmic components. Lysosomes Provide an Intracellular Digestive System. Lysosomes, which are found in great numbers in many cells, are small spherical vesicles surrounded by a membrane that contains digestive enzymes. These enzymes allow lysosomes to break down intracellular substances in structures, especially damaged cell structures, food particles that have been ingested by the cell, and unwanted materials such as bacteria. The membranes surrounding the lysosomes usually prevent the enclosed enzymes from coming in contact with other substances in the cell and therefore prevent their digestive action. When these membranes are dam- aged, the enzymes are released and split the organic substances with which they come in contact into highly diffusible substances such as amino acids and glucose. Mitochondria Release Energy in the Cell. An adequate supply of energy must be available to fuel the chemical reactions of the cell. This energy is provided mainly by the chemical reaction of oxygen with the three types of foods: glucose derived from carbohydrates, fatty acid derived from fats, and amino acids derived from proteins. After entering the cell, foods are split into smaller molecules that, in turn, enter the mitochondria, where other enzymes remove carbon dioxide and hydrogen ions in a process called the citric acid cycle. An oxidative enzyme system, which is also in the mitochondria, causes progressive oxidation of hydrogen atoms. The end products of mitochondria reactions are water and carbon dioxide. The energy liberated is used by mitochondria to synthesize another substance, adenosine triphosphate (ATP), a highly reactive chemical that can diffuse throughout the cell to release its energy whenever it is needed for the performance of cell functions.  The Cell and Its Functions 13 Mitochondria are also self-replicative, which means that one mitochondrion can form a second one, a third one, and so on whenever there is a need in the cell for increased amounts of ATP. There Are Many Cytoplasmic Structures and Organelles. Hundreds of types of cells are found in the body, and each has a special structure. Some cells, for example, are rigid and have large numbers of filamentous or tubular structures, which are composed of fibrillar proteins. A major function of these tubular structures is to act as a cytoskeleton, providing rigid physical structures for certain parts of cells. Some of the tubular structures, called microtubules, can transport substances from one area of the cell to another. One of the important functions of many cells is to secrete special substances, such as digestive enzymes. Almost all of the substances are formed by the ER- Golgi apparatus system and are released into the cyto- plasm inside storage vesicles called secretory vesicles. After a period of storage in the cell, they are expelled through the cell membrane to be used elsewhere in the body. The Nucleus Is the Control Center of the Cell and Contains Large Amounts of DNA, Also Called Genes (p. 17). Genes determine the characteristics of the proteins of the cell, including the enzymes of the cytoplasm. They also control reproduction. Genes first reproduce themselves through a process of mitosis in which two daughter cells are formed, each of which receives one of the two sets of genes. The nuclear membrane, also called the nuclear enve- lope, separates the nucleus from the cytoplasm. This structure is composed of two membranes; the outer membrane is continuous with the ER, and the space between the two nuclear membranes is also continuous with the compartment inside the ER. Both layers of the membrane are penetrated by several thousand nuclear pores, which are almost 100 nanometers in diameter. The nuclei in most cells contain one or more structures called nucleoli, which, unlike many of the organelles, do not have a surrounding membrane. The nucleoli contain large amounts of RNA and proteins of the type found in ribosomes. A nucleolus becomes enlarged when the cell is actively synthesizing proteins. Ribosomal RNA is stored in the nucleolus and trans- ported through the nuclear membrane pores to the cytoplasm, where it is used to produce mature ribo- somes, which play an important role in the formation of proteins. 14 UNIT I Introduction to Physiology: The Cell and General Physiology FUNCTIONAL SYSTEMS OF THE CELL (p. 19) Ingestion by the Cell—Endocytosis The cell obtains nutrients and other substances from the surrounding fluid through the cell membrane via diffusion and active transport. Very large particles · enter the cell viao endocytosis, the principal forms of which are pinocytosis and phagocytosis. Pinocytosis is the ingestion of small globules of ex- tracellular fluid, forming minute vesicles in the cell cytoplasm. This process is the only method by which large molecules, such as proteins, can enter the cells. These molecules usually attach to specialized recep- tors on the outer surface of the membrane that are concentrated in small pits called coated pits. On the inside of the cell membrane underneath these pits is a latticework of a fibrillar protein called clathrin and a contractile filament of actin and myosin. After the protein molecules bind with the receptors, the mem- brane invaginates and contractile proteins surround the pit, causing its borders to close over the attached proteins and form a pinocytotic vesicle. Phagocytosis is the ingestion of large particles, such as bacteria, cells, and portions of degenerating tissue. This ingestion occurs much in the same way as pino- cytosis except that it involves large particles instead of molecules. Only certain cells have the ability to perform phagocytosis, notably tissue macrophages and some white blood cells. Phagocytosis is initiated when proteins or large polysaccharides on the sur- face of the particle bind with receptors on the sur- face of the phagocyte. In the case of bacteria, these usually are attached to specific antibodies, and the antibodies in turn attach to the phagocyte receptors, dragging the bacteria along with them. This inter- mediation of antibodies is called opsonization and is discussed further in Chapters 34 and 35. Pinocytic and Phagocytic Foreign Substances Are Digested in the Cell by the Lysosomes. Almost as soon as pinocytic or phagocytic vesicles appear inside a cell, lysosomes become attached to the vesicles and empty their digestive enzymes into the vesicle. Thus, a digestive vesicle is formed in which the enzymes begin hydrolyzing the proteins, carbohydrates, lipids, and other substances in the vesicle. The products of digestion are small molecules of amino acids, glucose, phosphate, and so on that can diffuse through the membrane of the vesicle into the cytoplasm. The undigested substances, called the residual body, are excreted through the  The Cell and Its Functions 15 cell membrane via the process of exocytosis, which is basically the opposite of endocytosis. Synthesis of Cellular Structures by ER and Golgi Apparatus (p. 20) The Synthesis of Most Cell Structures Begins in the ER. Many of the products formed in the ER are then passed onto the Golgi apparatus, where they are further processed before release into the cytoplasm. The granular ER, characterized by large numbers of ⑥ ribosomes attached to the outer surface, is the site of protein formation. Ribosomes synthesize the proteins and extrude many of them through the wall of the ER to the interior of the endoplasmic vesicles and tubules, called the endoplasmic matrix. When proteins enter the ER, enzymes in the ER wall cause rapid changes, including congregation of carbo- hydrates to form glycoproteins. In addition, the proteins are often cross-linked, folded, and shortened to form more compact molecules. The ER also synthesizes lipids, especially phospho- lipid and cholesterol, which are incorporated into the lipid bilayer of the ER. Small ER vesicles, or transport vesicles, continually break off from the smooth reticu- lum. Most of these vesicles migrate rapidly to the Golgi apparatus. The Golgi Apparatus Processes Substances Formed in the ER. As substances are formed in the ER, especially proteins, they are transported through the reticulum tubules toward the portions of the smooth ER that lie nearest the Golgi apparatus. Small transport vesicles, composed of small envelopes of smooth ER, continually break away and diffuse to the deepest layer of the Golgi apparatus. The transport vesicles instantly fuse with the Golgi apparatus and empty their contents into the vesicular spaces of the Golgi apparatus. Here, more carbohydrates are added to the secretions, and the ER secretions are compacted. As the secretions pass toward the outermost layers of the Golgi apparatus, the compaction and processing continue. Finally, small and large vesicles break away from the Golgi apparatus, carrying with them the compacted secretory substances. These substances can then diffuse throughout the cell. In a highly secretory cell, the vesicles formed by the Golgi apparatus are mainly secretory vesicles, which dif- fuse to the cell membrane, fuse with it, and eventually empty their substances to the exterior via a mechanism called exocytosis. Some of the vesicles made in the Golgi 16 UNIT I Introduction to Physiology: The Cell and General Physiology apparatus, however, are destined for intracellular use. For example, specialized portions of the Golgi appara- tus form lysosomes. Extraction of Energy From Nutrients by the Mitochondria (p. 22) The principal substances from which the cells extract energy are oxygen and one or more of the foodstuffs— carbohydrates, fats, and proteins—that react with oxy- gen. In humans, almost all carbohydrates are converted to glucose by the digestive tract and liver before they reach the cell; similarly, proteins are converted to amino acids, and fats are converted to fatty acids. Inside the cell, these substances react chemically with oxygen under the influence of enzymes that control the rates of reaction and channel the released energy in the proper direction. Oxidative Reactions Occur Inside the Mitochondria, and Energy Released Is Used to Form ATP. ATP is a nucleotide composed of the nitrogenous base adenine, the pentose sugar ribose, and three phosphate radicals. The last two phosphate radicals are connected with the remainder of the molecule by high-energy phosphate bonds, each of which contains about 12,000 calories of energy per mole of ATP under the usual conditions of the body. The high-energy phosphate bonds are labile so they can be split instantly whenever energy is required to promote other cellular reactions. When ATP releases its energy, a phosphoric acid radical is split away, and adenosine diphosphate (ADP) is formed. Energy derived from cell nutrients causes the ADP and phosphoric acid to recombine to form new ATP, with the entire process continuing over and over again. Most of the ATP Produced in the Cell Is Formed in Mitochondria. After entry into the cells, glucose is < subjected to enzymes in the cytoplasm that convert it to pyruvic acid, a process called glycolysis. Less than 5 percent of the ATP formed in the cell occurs via glycolysis. Pyruvic acid derived from carbohydrates, fatty acids derived from lipids, and amino acids derived from proteins ↓are all eventually converted to the compound acetyl–coenzyme A (acetyl-CoA) in the mitochondria matrix. This substance is then acted on by another series of enzymes in a sequence of chemical reactions called the citric acid cycle, or Krebs cycle. In the citric acid cycle, acetyl-CoA is split into hydro- gen ions and carbon dioxide. Hydrogen ions are highly  The Cell and Its Functions 17 reactive and eventually combine with oxygen that has diffused into the mitochondria. This reaction releases a tremendous amount of energy, which is used to convert large amounts of ADP to ATP. This requires large num- bers of protein enzymes that are integral parts of the mitochondria. The oinitial event in ATP formation is removal of an electron from the hydrogen atom, thereby converting it to a hydrogen ion. The o terminal event is movement of the hydrogen ion through large globular proteins called ATP synthetase, which protrude through the mem- branes of the mitochondrial membranous shelves, which themselves protrude into the mitochondrial matrix. ATP synthetase is an enzyme that uses the energy and movement of the hydrogen ions to effect the conver- sion of ADP to ATP, and hydrogen ions combine with oxygen to form water. The newly formed ATP is trans- ported out of the mitochondria to all parts of the cell cytoplasm and nucleoplasm, where it is used to energize the functions of the cell. This overall process is called the chemosmotic mechanism of ATP formation. ATP Is Used for Many Cellular Functions. ATP promotes three types of cell function: (1) membrane transport, as occurs with the sodium-potassium pump, which transports sodium out of the cell and potassium into the cell; (2) synthesis of chemical compounds throughout the cell; and (3) mechanical work, as occurs with the contraction of muscle fibers or with ciliary and ameboid motion. Locomotion and Ciliary Movements of Cells (p. 24) The most obvious type of movement in the body is that of the specialized muscle cells in skeletal, cardiac, and smooth muscle, which constitute almost 50 percent of the entire body mass. Two other types of movement occur in other cells: ameboid locomotion and ciliary movement. Ameboid Movement of an Entire Cell in Relation to Its Surroundings. An example of ameboid locomotion is the movement of white blood cells through tissues. Typically, ameboid locomotion begins with protrusion of a pseudopodium from one end of the cell. This results from continual exocytosis, which forms a new cell membrane at the leading edge of the pseudopodium, and continual endocytosis of the membrane in the mid and rear portions of the cell. Two other effects are also essential to the forward ⑦ movement of the cell. The first effect is attachment 18 UNIT I Introduction to Physiology: The Cell and General Physiology of the pseudopodium to the surrounding tissues so it becomes fixed in its leading position while the remain- der of the cell body is pulled forward toward the point of attachment. This attachment is effected by receptor proteins that line the insides of the exocytotic vesicles. ① The second requirement for locomotion is avail- able energy needed to pull the cell body in the direction of the pseudopodium. In the cytoplasm of all cells are molecules of the protein actin. When these molecules polymerize to form a filamentous network, the net- work contracts when it binds with another protein, for example, an actin-binding protein such as myosin. The entire process, which is energized by ATP, takes place in the pseudopodium of a moving cell, in which such a network of actin filaments forms inside the growing pseudopodium. The most important factor that usually initiates ame- boid movement is the process called chemotaxis, which results from the appearance of certain chemical sub- stances in the tissue called chemotactic substances. Ciliary Movement Is a Whiplike Movement of Cilia on the Surfaces of Cells. Ciliary movement occurs in only two places in the body: on the inside surfaces of the respiratory airways and on the inside surfaces of the uterine tubes (i.e., the fallopian tubes of the reproductive tract). In the nasal cavity and lower respiratory airways, the whiplike motion of the cilia causes a layer of mucus to move toward the pharynx at a rate of about 1 cm/min; in this way, passageways with mucus or particles that become entrapped in the mucus are continually cleared. In the uterine tubes, the cilia cause slow movement of fluid from the ostium of the uterine tube toward the uterine cavity; it is mainly this movement of fluid that transports the ovum from the ovary to the uterus. The mechanism of the ciliary movement is not fully understood, but at least two factors are necessary: (1) available ATP and (2) appropriate ionic conditions, including appropriate concentrations of magnesium and calcium.