Each of the 100 trillion cells in a human being is a living structure that can survive for months or many years, provided its surrounding ﬂuids contain appropriate nutrients. To understand the function of organs and other structures of the body, it is essential that we ﬁrst understand the basic organization of the cell and the functions of its component parts.
Organization of the Cell
A typical cell, as seen by the light microscope, is shown in Figure 2–1. Its two major parts are the nucleus and the cytoplasm. The nucleus is separated from the cytoplasm by a nuclear membrane, and the cytoplasm is separated from the surrounding ﬂuids by a cell membrane, also called the plasma membrane. The different substances that make up the cell are collectively called protoplasm. Protoplasm is composed mainly of ﬁve basic substances: water, electrolytes, proteins, lipids, and carbohydrates.
The principal ﬂuid medium of the cell is water, which is present in most cells, except for fat cells, in a concentration of 70 to 85 per cent. Many cellular chemicals are dissolved in the water. Others are suspended in the water as solid particulates. Chemical reactions take place among the dissolved chemicals or at the surfaces of the suspended particles or membranes.
The most important ions in the cell are potassium, magnesium, phosphate, sulfate, bicarbonate, and smaller quantities of sodium, chloride, and calcium. These are all discussed in more detail in Chapter 4, which considers the interrelations between the intracellular and extracellular ﬂuids. The ions provide inorganic chemicals for cellular reactions. Also, they are necessary for operation of some of the cellular control mechanisms. For instance, ions acting at the cell membrane are required for transmission of electrochemical impulses in nerve and muscle ﬁbers.
After water, the most abundant substances in most cells are proteins, which normally constitute 10 to 20 per cent of the cell mass. These can be divided into two types: structural proteins and functional proteins. Structural proteins are present in the cell mainly in the form of long ﬁlaments that themselves are polymers of many individual protein molecules. A prominent use of such intracellular ﬁlaments is to form microtubules that provide the “cytoskeletons” of such cellular organelles as cilia, nerve axons, the mitotic spindles of mitosing cells, and a tangled mass of thin ﬁlamentous tubules that hold the parts of the cytoplasm and nucleoplasm together in their respective compartments. Extracellularly, ﬁbrillar proteins are found especially in the collagen and elastin ﬁbers of connective tissue and in blood vessel walls, tendons, ligaments, and so forth. The functional proteins are an entirely different type of protein, usually composed of combinations of a few molecules in tubular-globular form. These proteins are mainly the enzymes of the cell and in contrast to the ﬁbrillar proteins, are often mobile in the cell ﬂuid. Also, many of them are adherent to membranous structures inside the cell. The enzymes come into direct contact with other substances in the cell ﬂuid and thereby catalyze speciﬁc intracellular chemical reactions. For instance, the chemical reactions that split glucose into its component parts and then combine these with oxygen to form carbon dioxide and water while simultaneously providing energy for cellular function are all catalyzed by a series of protein enzymes.
Lipids are several types of substances that are grouped together because of their common property of being soluble in fat solvents. Especially important lipids are phospholipids and cholesterol, which together constitute only about 2 per cent of the total cell mass. The signiﬁcance of phospholipids and cholesterol is that they are mainly insoluble in water and, therefore, are used to form the cell membrane and intracellular membrane barriers that separate the different cell compartments. In addition to phospholipids and cholesterol, some cells contain large quantities of triglycerides, also called neutral fat. In the fat cells, triglycerides often account for as much as 95 per cent of the cell mass. The fat stored in these cells represents the body’s main storehouse of energy-giving nutrients that can later be dissoluted and used to provide energy wherever in the body it is needed.
Carbohydrates have little structural function in the cell except as parts of glycoprotein molecules, but they play a major role in nutrition of the cell. Most human cells do not maintain large stores of carbohydrates; the amount usually averages about 1 per cent of their total mass but increases to as much as 3 per cent in muscle cells and, occasionally, 6 per cent in liver cells. However, carbohydrate in the form of dissolved glucose is always present in the surrounding extracellular ﬂuid so that it is readily available to the cell. Also, a small amount of carbohydrate is virtually always stored in the cells in the form of glycogen, which is an insoluble polymer of glucose that can be depolymerized and used rapidly to supply the cells’ energy needs.
Physical Structure of the Cell
The cell is not merely a bag of ﬂuid, enzymes, and chemicals; it also contains highly organized physical structures, called intracellular organelles. The physical nature of each organelle is as important as the cell’s chemical constituents for cell function. For instance, without one of the organelles, the mitochondria, more than 95 per cent of the cell’s energy release from nutrients would cease immediately.
Membranous Structures of the Cell
Most organelles of the cell are covered by membranes composed primarily of lipids and proteins. These membranes include the cell membrane, nuclear membrane, membrane of the endoplasmic reticulum, and membranes of the mitochondria, lysosomes, and Golgi apparatus. The lipids of the membranes provide a barrier that impedes the movement of water and water-soluble substances from one cell compartment to another because water is not soluble in lipids. However, protein molecules in the membrane often do penetrate all the way through the membrane, thus providing specialized pathways, often organized into actual pores, for passage of speciﬁc substances through the membrane. Also, many other membrane proteins are enzymes that catalyze a multitude of different chemical reactions, discussed here and in subsequent articles.
Cell Membrane The cell membrane (also called the plasma membrane), which envelops the cell, is a thin, pliable, elastic structure only 7.5 to 10 nanometers thick. It is composed almost entirely of proteins and lipids. The approximate composition is proteins, 55 per cent; phospholipids, 25 per cent; cholesterol, 13 per cent; other lipids, 4 per cent; and carbohydrates, 3 per cent.
Lipid Barrier of the Cell Membrane Impedes Water Penetration.
Its basic structure is a lipid bilayer, which is a thin, double-layered ﬁlm of lipids—each layer only one molecule thick—that is continuous over the entire cell surface. Interspersed in this lipid ﬁlm are large globular protein molecules. The basic lipid bilayer is composed of phospholipid molecules. One end of each phospholipid molecule is soluble in water; that is, it is hydrophilic. The other end is soluble only in fats; that is, it is hydrophobic. The phosphate end of the phospholipid is hydrophilic, and the fatty acid portion is hydrophobic. Because the hydrophobic portions of the phospholipid molecules are repelled by water but are mutually attracted to one another, they have a natural tendency to attach to one another in the middle of the membrane. The hydrophilic phosphate portions then constitute the two surfaces of the complete cell membrane, in contact with intracellular water on the inside of the membrane and extracellular water on the outside surface. The lipid layer in the middle of the membrane is impermeable to the usual water-soluble substances, such as ions, glucose and urea. Conversely, fat-soluble substances, such as oxygen, carbon dioxide, and alcohol, can penetrate this portion of the membrane with ease. The cholesterol molecules in the membrane are also lipid in nature because their steroid nucleus is highly fat soluble. These molecules, in a sense, are dissolved in the bilayer of the membrane. They mainly help determine the degree of permeability (or impermeability) of the bilayer to water-soluble constituents of body ﬂuids. Cholesterol controls much of the ﬂuidity of the membrane as well.
Cell Membrane Proteins
The diagram also shows globular masses ﬂoating in the lipid bilayer. These are membrane proteins, most of which are glycoproteins.
Two types of proteins occur: integral proteins that protrude all the way through the membrane and peripheral proteins that are attached only to one surface of the membrane and do not penetrate all the way through. Many of the integral proteins provide structural channels (or pores) through which water molecules and water-soluble substances, especially ions, can diffuse between the extracellular and intracellular ﬂuids. These protein channels also have selective properties that allow preferential diffusion of some substances over others. Other integral proteins act as carrier proteins for transporting substances that otherwise could not penetrate the lipid bilayer. Sometimes these even transport substances in the direction opposite to their natural direction of diffusion, which is called “active transport.” Still others act as enzymes.
Integral membrane proteins can also serve as receptors for water-soluble chemicals, such as peptide hormones, that do not easily penetrate the cell membrane. Interaction of cell membrane receptors with speciﬁc ligands that bind to the receptor causes conformational changes in the receptor protein. This, in turn, enzymatically activates the intracellular part of the protein or induces interactions between the receptor and proteins in the cytoplasm that act as second messengers, thereby relaying the signal from the extracellular part of the receptor to the interior of the cell. In this way, integral proteins spanning the cell membrane provide a means of conveying information about the environment to the cell interior. Peripheral protein molecules are often attached to the integral proteins. These peripheral proteins function almost entirely as enzymes or as controllers of transport of substances through the cell membrane “pores.”
Membrane Carbohydrates—the Cell “Glycocalyx.”
Membrane carbohydrates occur almost invariably in combination with proteins or lipids in the form of glycoproteins or glycolipids. In fact, most of the integral proteins are glycoproteins and about one tenth of the membrane lipid molecules are glycolipids. The “glyco” portions of these molecules almost invariably protrude to the outside of the cell, dangling outward from the
cell surface. Many other carbohydrate compounds, called proteoglycans—which are mainly carbohydrate substances bound to small protein cores—are loosely attached to the outer surface of the cell as well. Thus, the entire outside surface of the cell often has a loose carbohydrate coat called the glycocalyx. The carbohydrate moieties attached to the outer surface of the cell have several important functions:
(1) Many of them have a negative electrical charge, which gives most cells an overall negative surface charge that repels other negative objects.
(2) The glycocalyx of some cells attaches to the glycocalyx of other cells, thus attaching cells to one another.
(3) Many of the carbohydrates act as receptor substances for binding hormones, such as insulin; when bound, this combination activates attached internal proteins that, in turn, activate a cascade of intracellular enzymes.
(4) Some carbohydrate moieties enter into immune reactions.
Cytoplasm and Its Organelles
The cytoplasm is ﬁlled with both minute and large dispersed particles and organelles. The clear ﬂuid portion of the cytoplasm in which the particles are dispersed is called cytosol; this contains mainly dissolved proteins, electrolytes, and glucose. Dispersed in the cytoplasm are neutral fat globules, glycogen granules, ribosomes, secretory vesicles, and ﬁve especially important organelles: the endoplasmic reticulum, the Golgi apparatus, mitochondria, lysosomes, and peroxisomes.
Diagram shows a network of tubular and ﬂat vesicular structures in the cytoplasm; this is the endoplasmic reticulum. The tubules and vesicles interconnect with one another. Also, their walls are constructed of lipid bilayer membranes that contain large amounts of proteins, similar to the cell membrane. The total surface area of this structure in some cells the liver cells, for instance can be as much as 30 to 40 times the cell membrane area. The detailed structure of a small portion of endoplasmic reticulum is shown in diagram. The space inside the tubules and vesicles is ﬁlled with endoplasmic matrix, a watery medium that is different from the ﬂuid in the cytosol outside the endoplasmic reticulum. Electron micrographs show that the space inside the endoplasmic reticulum is connected with the space between the two membrane surfaces of the nuclear membrane. Substances formed in some parts of the cell enter the space of the endoplasmic reticulum and are then conducted to other parts of the cell. Also, the vast surface area of this reticulum and the multiple enzyme systems attached to its membranes provide machinery for a major share of the metabolic functions of the cell.
Ribosomes and the Granular Endoplasmic Reticulum
Attached to the outer surfaces of many parts of the endoplasmic reticulum are large numbers of minute granular particles called ribosomes. Where these are present, the reticulum is called the granular endoplasmic reticulum. The ribosomes are composed of a mixture of RNA and proteins, and they function to synthesize new protein molecules in the cell.
Agranular Endoplasmic Reticulum
Part of the endoplasmic reticulum has no attached ribosomes. This part is called the agranular, or smooth, endoplasmic reticulum. The agranular reticulum functions for the synthesis of lipid substances and for other processes of the cells promoted by intrareticular enzymes.
The Golgi apparatus, is closely related to the endoplasmic reticulum. It has membranes similar to those of the agranular endoplasmic reticulum. It usually is composed of four or more stacked layers of thin, ﬂat, enclosed vesicles lying near one side of the nucleus. This apparatus is prominent in secretory cells, where it is located on the side of the cell from which the secretory substances are extruded. The Golgi apparatus functions in association with the endoplasmic reticulum. Shown in the diagram, small “transport vesicles” (also called endoplasmic reticulum vesicles, or ER vesicles) continually pinch off from the endoplasmic reticulum and shortly thereafter fuse with the Golgi apparatus. In this way, substances entrapped in the ER vesicles are transported from the endoplasmic reticulum to the Golgi apparatus. The transported substances are then processed in the Golgi apparatus to form lysosomes, secretory vesicles, and other cytoplasmic components.
Lysosomes, shown in diagram, are vesicular organelles that form by breaking off from the Golgi apparatus and then dispersing throughout the cytoplasm.
The lysosomes provide an intracellular digestive system that allows the cell to digest
(1) Damaged cellular structures,
(2) Food particles that have been ingested by the cell and
(3) Unwanted matter such as bacteria.
The lysosome is quite different in different types of cells, but it is usually 250 to 750 nanometers in diameter. It is surrounded by a typical lipid bilayer membrane and is ﬁlled with large numbers of small granules 5 to 8 nanometers in diameter, which are protein aggregates of as many as 40 different hydrolase (digestive) enzymes. A hydrolytic enzyme is capable of splitting an organic compound into two or more parts by combining hydrogen from a water molecule with one part of the compound and combining the hydroxyl portion of the water molecule with the other part of the compound. For instance, protein is hydrolyzed to form amino acids, glycogen is hydrolyzed to form glucose and lipids are hydrolyzed to form fatty acids and glycerol. Ordinarily, the membrane surrounding the lysosome prevents the enclosed hydrolytic enzymes from coming in contact with other substances in the cell and, therefore, prevents their digestive actions. However, some conditions of the cell break the membranes of some of the lysosomes, allowing release of the digestive enzymes. These enzymes then split the organic substances with which they come in contact into small, highly diffusible substances such as amino acids and glucose. Some of the more speciﬁc functions of lysosomes are discussed later in the chapter.
Peroxisomes are similar physically to lysosomes, but they are different in two important ways. First, they are believed to be formed by self-replication (or perhaps by budding off from the smooth endoplasmic reticulum) rather than from the Golgi apparatus. Second, they contain oxidases rather than hydrolases. Several of the oxidases are capable of combining oxygen with hydrogen ions derived from different intracellular chemicals to form hydrogen peroxide (H2O2). Hydrogen peroxide is a highly oxidizing substance and is used in association with catalase, another oxidase enzyme present in large quantities in peroxisomes, to oxidize many substances that might otherwise be poisonous to the cell. For instance, about half the alcohol a person drinks is detoxiﬁed by the peroxisomes of the liver cells in this manner.
Secretory Vesicles One of the important functions of many cells is secretion of special chemical substances. Almost all such secretory substances are formed by the endoplasmic reticulum–Golgi apparatus system and are then released from the Golgi apparatus into the cytoplasm in the form of storage vesicles called secretory vesicles or secretory granules. Diagram shows typical secretory vesicles inside pancreatic acinar cells; these vesicles store protein proenzymes (enzymes that are not yet activated).The proenzymes are secreted later through the outer cell membrane into the pancreatic duct and thence into the duodenum, where they become activated and perform digestive functions on the food in the intestinal tract.
The mitochondria, shown in diagram, are called the “powerhouses” of the cell. Without them, cells would be unable to extract enough energy from the nutrients, and essentially all cellular functions would cease. Mitochondria are present in all areas of each cell’s cytoplasm, but the total number per cell varies from less than a hundred up to several thousand, depending on the amount of energy required by the cell. Further, the mitochondria are concentrated in those portions of the cell that are responsible for the major share of its energy metabolism. They are also variable in size and shape. Some are only a few hundred nanometers in diameter and globular in shape, whereas others are elongated—as large as 1 micrometer in diameter and 7 micrometers long; still others are branching and ﬁlamentous. The basic structure of the mitochondrion, shown in diagram, is composed mainly of two lipid bilayer–protein membranes: an outer membrane and an inner membrane. Many in folding of the inner membrane form shelves onto which oxidative enzymes are attached. In addition, the inner cavity of the mitochondrion is ﬁlled with a matrix that contains large quantities of dissolved enzymes that are necessary for extracting energy from nutrients. These enzymes operate in association with the oxidative enzymes on the shelves to cause oxidation of the nutrients, thereby forming carbon dioxide and water and at the same time releasing energy. The liberated energy is used to synthesize a “high-energy” substance called adenosine triphosphate (ATP). ATP is then transported out of the mitochondrion, and it diffuses throughout the cell to release its own energy wherever it is needed for performing cellular functions. (The chemical details of ATP formation by the mitochondrion are given in other article), but some of the basic functions of ATP in the cell are introduced later in this chapter. Mitochondria are 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. Indeed, the mitochondria contain DNA similar to that found in the cell nucleus. DNA is the basic chemical of the nucleus that controls replication of the cell. The DNA of the mitochondrion plays a similar role, controlling replication of the mitochondrion itself.
Filament and Tubular Structures of the Cell
The ﬁbrillar proteins of the cell are usually organized into ﬁlaments or tubules. These originate as precursor protein molecules synthesized by ribosomes in the cytoplasm. The precursor molecules then polymerize to form ﬁlaments. As an example, large numbers of actin ﬁlaments frequently occur in the outer zone of the cytoplasm, called the ectoplasm, to form an elastic support for the cell membrane. Also, in muscle cells, actin and myosin ﬁlaments are organized into a special contractile machine that is the basis for muscle contraction. A special type of stiff ﬁlament composed of polymerized tubulin molecules is used in all cells to construct very strong tubular structures, the microtubules. Diagram shows typical microtubules that were teased from the ﬂagellum of a sperm. Another example of microtubules is the tubular skeletal structure in the center of each cilium that radiates upward from the cell cytoplasm to the tip of the cilium. This structure is discussed later in the chapter and is illustrated in diagram. Also, both the centrioles and the mitotic spindle of the mitosing cell are composed of stiff microtubules. Thus, a primary function of microtubules is to act as a cytoskeleton, providing rigid physical structures for certain parts of cells.
The nucleus is the control center of the cell. Brieﬂy, the nucleus contains large quantities of DNA, which are the genes. The genes determine the characteristics of the cell’s proteins, including the structural proteins, as well as the intracellular enzymes that control cytoplasmic and nuclear activities. The genes also control and promote reproduction of the cell itself. The genes ﬁrst reproduce to give two identical sets of genes; then the cell splits by a special process called mitosis to form two daughter cells, each of which receives one of the two sets of DNA genes. All these activities of the nucleus are considered in detail in the next chapter. Unfortunately, the appearance of the nucleus under the microscope does not provide many clues to the mechanisms by which the nucleus performs its control activities. Diagram shows the light microscopic appearance of the interphase nucleus (during the period between mitoses), revealing darkly staining chromatin material throughout the nucleoplasm. During mitosis, the chromatin material organizes in the form of highly structured chromosomes, which can then be easily identiﬁed using the light microscope, as illustrated in the next chapter.
The nuclear membrane, also called the nuclear envelope, is actually two separate bilayer membranes, one inside the other. The outer membrane is continuous with the endoplasmic reticulum of the cell cytoplasm, and the space between the two nuclear membranes is also continuous with the space inside the endoplasmic reticulum, as shown in diagram.
The nuclear membrane is penetrated by several thousand nuclear pores. Large complexes of protein molecules are attached at the edges of the pores so that the central area of each pore is only about 9 nanometers in diameter. Even this size is large enough to allow molecules up to 44,000 molecular weight to pass through with reasonable ease.
Nucleoli and Formation of Ribosomes
The nuclei of most cells contain one or more highly staining structures called nucleoli. The nucleolus, unlike most other organelles discussed here, does not have a limiting membrane. Instead, it is simply an accumulation of large amounts of RNA and proteins of the types found in ribosomes. The nucleolus becomes considerably enlarged when the cell is actively synthesizing proteins. Formation of the nucleoli (and of the ribosomes in the cytoplasm outside the nucleus) begins in the nucleus. First, speciﬁc DNA genes in the chromosomes cause RNA to be synthesized. Some of this is stored in the nucleoli, but most of it is transported outward through the nuclear pores into cytoplasm. Here, it is used in conjunction with speciﬁc proteins to assemble “mature” ribosomes that play an essential role in forming cytoplasmic proteins.
BASIC SCHEME OF STRUCTURE OF CELL
STRUCTURAL ARRANGEMENT OF CELL ORGANELLES
PHOSPHOLIPID BILAYER (CELL MEMBRANE)
ROUGH ENDOPLASMIC RETICULUM
ARRANGEMENT OF RER & SER
FORMATION OF SECRETORY VESICLES
STRUCTURE OF MITOCHONDRIUM
NUCLEUS & NUCLEAR MEMBRANE