Overview of the Digestive System http://arbl.cvmbs.colostate.edu/hbooks/pathphys/digestion/index.

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Consider for a moment a Big Mac. The purpose in your eating a Big Mac, other than simple hedonism, is to assimlate the nutrients it represents and make them available to build, repair and maintain your own tissues, as well as provide energy for studying and occasional other pursuits. You may have asked yourself - "Exactly what nutients are present in a Big Mac that I can assimilate?" MacDonald's comes close to full disclosure in this regard, but what they don't tell you is that in order to take advantage of these nutrients, you have to provide the means to carefully break them down into much smaller molecules that can be imported into blood. Luckily, your digestive system takes care of this very complex process so efficiently that most of the time you don't even need to think about it. At its simplest, the digestive system it is a tube running from mouth to anus. This tube is like an assembly line, or more properly, a dissembly line. Its chief goal is to break down huge macromolecules (proteins, fats and starch), which cannot be absorbed intact, into smaller molecules (amino acids, fatty acids and glucose) that can be absorbed across the wall of the tube, and into the circulatory system for dissemination around your body.

The breakdown of foodstuffs like a Big Mac is accomplished through a combination of mechanical and enzymatic processes. To accomplish this breakdown, the digestive tube requires considerable assistance from accessory digestive organs such as the salivary glands, liver and pancreas, which dump their secretions into the tube. The name "accessory" should not be taken to mean dispensible; indeed, without pancreatic enzymes you would starve to death in short order. In many ways, the digestive system can be thought of as a well-run factory in which a large number of complex tasks are performed. The three fundamental processes that take place are: Secretion: Delivery of enzymes, mucus, ions and the like into the lumen, and hormones into blood. Absorption: Transport of water, ions and nutrients from the lumen, across the

epithelium and into blood. Motility: Contractions of smooth muscle in the wall of the tube that crush, mix and propel its contents.

Each part of the digestive tube performs at least some of these tasks, and different regions of the tube have unique and important specializations. Like any well-run factory, proper function of the digestive system requires robust control systems. Control systems must facilitate communication among different sections of the digestive tract (i.e. control on the factory floor), and between the digestive tract and the brain (i.e. between workers and managment). Control of digestive function is achieved through a combination of electrical and hormonal messages which originate either within the digestive system's own nervous and endocrine systems, as well as from the central nervous sytem and from endocrine organs such as the adrenal gland. Different parts of these systems are constantly talking to one another. The basic messages are along the lines of "I just received an extraordinary load of food, so I suggest you get prepared" (stomach to large intestine) or "For goodness sake, please slow down until I can catch up with what you've already given me" (small intestine to stomach). Finally, a note about differences in digestive anatomy and physiology among animals. The digestive systems of humans, dogs, mice, horses, kangaroos and great white sharks are, to a first approximation, virtually identical. If you look more carefully however, it becomes apparent that each of these species has evolved certain digestive specializations that have allowed it to adapt to a particular diet. These differences become particularly apparent when you compare a carnivore like a cat with a herbivore like a goat or a horse. Goats and horses evolved from ancestors that subsisted on plants and adapted parts of their digestive tracts into massive fermentation vats which enabled them efficiently utilize cellulose, the major carbohydrate of plants. In contrast, cats evolved from animals that lived on the carcasses of other animals, and have digestive systems that reflect this history - extremely small fermentation vats and essentially no ability to utilize cellulose. Bridging the gap between carnivores and herbivores are omnivores like humans and pigs, whose digestive tracts attest to a historical diet that included both plants and animals. The image above shows a young omnivore in the company of herbivore and carnivore friends. Microanatomy of the Digestive Tube Remarkably diverse and specialized processes take place in different sections of the digestive tract, but there is a fundamental consistency in the architecture of the tubular digestive tract. With few exceptions, the wall of the digestive tube from the mouth to the anus is composed of four basic layers or tunics.

Tunica serosa is the outermost covering of the digestive tube. In most of the digestive tract (stomach and intestines) it consists of a thin layer of loose connective tissue covered by mesothelium (a type of squamous epithelium that lines body cavities); within the peritoneal cavity, this structure is also referred to as visceral peritoneum. In the abdominal cavity, the serosa on each side of the tube fuses together to form a suspensory structure called mesentery, which houses vascular and nervous supplies to the digestive tract and is continuous with the lining of the cavity. In regions outside of the abdominal cavity where the the digestive tube is essentially affixed to adjacent structures via its outer layer of connective tissue (esophagus and rectum), this tunic is referred to as tunica adventitia instead of tunica serosa. Tunica muscularis endows the digestive tube with an ability to be motile. In most of the digestive tube, this tunic consists of two thick layers of smooth muscle. Muscle fibers in the inner layer are aligned circularly, whereas those in the outer layer have a longitudinal orientation. This combination of circular and longitudinal smooth muscle gives the tube an ability to perform complex movements that squeeze and propel ingesta in the lumen. Between the inner circular and outer longitudinal layers of smooth muscle is another critical component of the digestive tract's nervous system the myenteric plexus. Tunica submucosa lies immediately beneath the mucosa, and is a layer of loose to dense connective tissue containing blood and lymphatic vessels. The submucosa also contains the submucous plexus, a critical component of the digestive tract's nervous system which provides nervous control to the mucosa. Tunica mucosa is the innermost layer of the digestive tube and lines the lumen. Among the four tunics, the mucosa is most variable in structure and function, endowing the tube with an ability to perform diverse and specialized digestive tasks along its length. Of critical importance in this regard are the epithelial cells that cover the mucosa and are thus in direct contact with the lumen. This epithelial cell sheet (lamina epithelialis) is distinctly different in different regions of the tract. Indeed, in most of the tract, several different cell types contribute to the epithelium, including cells dedicated to secretion, absorption or production of

hormones. These distinctive differences in architecture of the epithelium can be seen below in the micrographs of mouse digestive tube. The magnification of all four images is identical and the epithelial layer is oriented toward the top.

Beneath the epithelium, but still within the tunica mucosa is a layer - the lamina propria - of loose connective tissue through which course blood vessels and lymphatics that supply the epithelium. This layer also contains lymphatic nodules important to immune functions of the digestive tract. Finally, beneath the lamina propropria is a thin layer of smooth muscle ( lamina muscularis mucosae) which permits the mucosa to dynamically move and fold.

The digestive system is composed of the digestive or alimentary tube and accessory digestive organs. The basic terminology used to describe parts of the digestive system is shown below and more detailed description of each is presented in later sections.

The digestive system depicted above - a carnivore - is the simplist among mammals. Other species, even humans, have a more or very much more extensive large intestine, and ruminants like cattle and sheep have a large set of forestomachs through which food passes before it reaches the stomach. Each of the organs shown above contributes to the digestive process in several unique ways. If you were to describe their most important or predominant function, and summarize shamelessly, the list would look something like this: Mouth: Foodstuffs are broken down mechanically by chewing and saliva is added as a lubricant. In some species, saliva contains amylase, an enzyme that digests starch. Esophagus: A simple conduit between the mouth and stomach - clearly important but only marginally interesting compared to other regions of the tube. Stomach: Where the real action begins - enzymatic digestion of proteins initiated and foodstuffs reduced to liquid form. Liver: The center of metabolic activity in the body - its major role in the digestive process is to provide bile salts to the small intestine, which are critical for digestion and absorption of fats. Pancreas: Important roles as both an endocrine and exocrine organ - provides a potent mixture of digestive enzymes to the small intestine which are critical for digestion of fats, carbohydrates and protein. Small Intestine: The most exciting place to be in the entire digestive system - this is where the final stages of chemical enzymatic digestion occur and where almost almost all nutrients are absorbed. Large Intestine: Major differences among species in extent and importance - in all animals water is absorbed, bacterial fermentation takes place and feces are formed. In carnivores, that's about the extent of it, but in herbivores like the horse, the large intestine is huge and of critical importance for utilization of cellulose.

Microanatomy of the Digestive Tube

Remarkably diverse and specialized processes take place in different sections of the digestive tract, but there is a fundamental consistency in the architecture of the tubular digestive tract. With few exceptions, the wall of the digestive tube from the mouth to the anus is composed of four basic layers or tunics.

Tunica serosa is the outermost covering of the digestive tube. In most of the digestive tract (stomach and intestines) it consists of a thin layer of loose connective tissue covered by mesothelium (a type of squamous epithelium that lines body cavities); within the peritoneal cavity, this structure is also referred to as visceral peritoneum. In the abdominal cavity, the serosa on each side of the tube fuses together to form a suspensory structure called mesentery, which houses vascular and nervous supplies to the digestive tract and is continuous with the lining of the cavity. In regions outside of the abdominal cavity where the the digestive tube is essentially affixed to adjacent structures via its outer layer of connective tissue (esophagus and rectum), this tunic is referred to as tunica adventitia instead of tunica serosa. Tunica muscularis endows the digestive tube with an ability to be motile. In most of the digestive tube, this tunic consists of two thick layers of smooth muscle. Muscle fibers in the inner layer are aligned circularly, whereas those in the outer layer have a longitudinal orientation. This combination of circular and longitudinal smooth muscle gives the tube an ability to perform complex movements that squeeze and propel ingesta in the lumen. Between the inner circular and outer longitudinal layers of smooth muscle is another critical component of the digestive tract's nervous system the myenteric plexus. Tunica submucosa lies immediately beneath the mucosa, and is a layer of loose to dense connective tissue containing blood and lymphatic vessels. The submucosa also contains the submucous plexus, a critical component of the digestive tract's nervous system which provides nervous control to the mucosa. Tunica mucosa is the innermost layer of the digestive tube and lines the lumen. Among the four tunics, the mucosa is most variable in structure and function, endowing the tube with an ability to perform diverse and specialized digestive

tasks along its length. Of critical importance in this regard are the epithelial cells that cover the mucosa and are thus in direct contact with the lumen. This epithelial cell sheet (lamina epithelialis) is distinctly different in different regions of the tract. Indeed, in most of the tract, several different cell types contribute to the epithelium, including cells dedicated to secretion, absorption or production of hormones. These distinctive differences in architecture of the epithelium can be seen below in the micrographs of mouse digestive tube. The magnification of all four images is identical and the epithelial layer is oriented toward the top.

Beneath the epithelium, but still within the tunica mucosa is a layer - the lamina propria - of loose connective tissue through which course blood vessels and lymphatics that supply the epithelium. This layer also contains lymphatic nodules important to immune functions of the digestive tract. Finally, beneath the lamina propropria is a thin layer of smooth muscle ( lamina muscularis mucosae) which permits the mucosa to dynamically move and fold.

Microbial Life in the Digestive Tract The gastrointestinal tract contains an immensely complex ecology of microorganisms. A typical person harbors more than 500 distinct species of bacteria, representing dozens of different lifestyles and capabilities. The composition and distribution of this menagerie varies with age, state of health and diet. The number and type of bacteria in the gastrointestinal tract vary dramatically by region. In healthy individuals the stomach and proximal small intestine contain few microorganisms, largely a result of the bacteriocidal activity of gastric acid; those that are present are aerobes and facultative anaerobes. One interesting testimony to the ability of gastric acid to suppress bacterial populations is seen in patients with achlorhydria, a genetic condition which prevents secretion of gastric acid. Such patients, which are otherwise healthy, may have as many as 10,000 to 100,000,000 microorganisms per ml of stomach contents.

In sharp contrast to the stomach and small intestine, the contents of the colon literally teem with bacteria, predominantly strict anaerobes (bacteria that survive only in environments virtually devoid of oxygen). Between these two extremes is a transitional zone, usually in the ileum, where moderate numbers of both aerobic and anaerobic bacteria are found. Microbial Populations in the Digestive Tract of Normal Humans Stomach Viable bacteria per gram pH 0 - 103 3.0 Jejunum 0 - 104 6.0-7.0 Ileum 105 - 108 7.5 Colon 1010 - 1012 6.8-7.3

The gastrointestinal tract is sterile at birth, but colonization typically begins within a few hours of birth, starting in the small intestine and progressing caudally over a period of several days. In most circumstances, a "mature" microbial flora is established by 3 to 4 weeks of age. It is also clear that microbial populations exert a profound effect on structure and function of the digestive tract. For example: The morphology of the intestine of germ-free animals differs considerably from normal animals - villi of the small intestine are remarkably regular, the rate of epithelial cell renew is reduced and, as one would expect, the number and size of Peyer's patches is reduced. The cecum of germ-free rats is roughly 10 times the size of that in a conventional rat. Bacteria in the intestinal lumen metabolize a variety of sterols and steroids. For example, bacteria convert the bile salt cholic acid to deoxycholic acid. Small intestinal bacteria also have a important role in sex steroid metabolism.

Finally, bacterial populations in the large intestine digest carbohydrates, proteins and lipids that escape digestion and absorption in small intestine. This fermentation, particularly of cellulose, is of critical importance to herbivores like cattle and horses which make a living by consuming plants. However, it seems that even species like humans and rodents derive significant benefit from the nutrients liberated by intestinal microorganisms.

Review of Food Chemistry "I didn't fight my way to the top of the food chain to become a vegetarian" The diet of any animal contains hundreds if not thousands of different molecules, but the bulk of the ingested nutrients are in the form of huge macromolecules that cannot be absorbed into blood without first being reduced to much simpler and smaller forms even table sugar (sucrose) cannot be absorbed without first being enzymatically ripped apart into glucose and fructose. The most important enzymatic reaction in digestion of foodstuffs is hydrolysis the breaking of a chemical bond by the addition of a water molecule. Proteins Proteins are polymers of amino acids linked together by peptide bonds. Chain length varies tremendously and many dietary proteins have been modified after translation by addition of

carbohydrate (glycoproteins) or lipid (lipoprotein) moieties. These modifications will be almost totally ignored in this text. Very short proteins, typically 3 to 10 amino acids in length, are called peptides. Although very small peptides can be absorbed to a limited degree, for all intents and purposes, proteins must be reduced to single amino acids before they can be absorbed. Enzymes that hydrolyze peptide bonds and reduce proteins or peptides to amino acids are called proteases or peptidases.

Lipids Fatty acids are present in only small amounts in animal and plant tissues, but are the building blocks of many important complex lipids. True fatty acids possess a long hydrocarbon chain terminating in a carboxyl group. Nearly all fatty acids have an even number of carbons and have chains between 14 and 22 carbons in length. The principle differences among the many fatty acids are the length of the chain (usually 16 or 18 carbons) and the positions of unsaturated or double bonds. For example, stearic acid (pictured below) has 18 carbons and is saturated.

The so-called "short-chain" or volatile fatty acids are 2 to 4-carbon molecules of great importance in intermediary metabolism and as the mainstay of ruminant nutrition. They are represented by acetic, butyric and proprionic acids. The most abundant storage form of fat in animals and plants, and hence the most important dietary lipid, is neutral fat or triglyceride. A molecule of triglyceride is composed of a molecule of glycerol in which each of the three carbons is linked through an ester bond to a fatty acid. Triglycerides cannot be efficiently absorbed, and are enzymatically digested by pancreatic lipase into a 2-monoglyceride and two free fatty acids, all of which can be absorbed. Other lipases hydrolyse a triglyceride into glycerol and three fatty acids. A triglyceride (triacylglycerol): tristearin

Carbohydrates The diversity of dietary carbohydrates necessitates discussion of several classes of these molecules, ranging from simple sugars to huge, branched polymers. Monosaccharides or simple sugars are either hexoses (6-carbon) like glucose, galactose and fructose, or pentoses (5-carbon) like ribose. These are the breakdown products of more complex carbohydrates and can be efficiently absorbed across the wall of the digestive tube and transported into blood. Disaccharides are simply two monosaccharides linked together by a glycosidic bond. The disaccharides most important in nutrition and digestion are: lactose or "milk sugar": glucose + galactose sucrose or "table sugar": glucose + fructose maltose: glucose + glucose

Oligosaccharides, which include disaccharides, are relatively short chains of monosaccharides which typically are intermediates in the breakdown of polysaccharides to monosaccharides. Polysaccharides are the most abundant dietary carbohydrate for all except very young animals. You should be familiar with three important polysaccharides, each of which is a large polymer of glucose: Starch is a major plant storage form of glucose. It occurs in two forms: alpha-amylose, in which the glucoses are linked together in straight chains, and amylopectin, in which the glucose chains are highly branched. Except for the branch points of amylopectin, the glucose monomers in starch are linked via alpha(1-4) glycosidic bonds, which, in the digestive tract of mammals, are hydrolyzed by amylases. Cellulose is the other major plant carbohydrate. It is the major constituent of plant cell walls, and more than half of the organic carbon on earth is found in cellulose. Cellulose is composed on unbranched, linear chains of D-glucose molecules, linked to one another by beta(1-4) glycosidic bonds, which no vertebrate has the capacity to enzymatically digest. Herbivores subsist largely on cellulose, not because they can digest it themselves, but because their digestive tracts teem with microbes that produce cellulases that hydrolyze cellulose. Glycogen is the third large polymer of glucose and is the major animal storage carbohydrate. Like starch, the glucose molecules in glycogen are linked together by alpha(1-4) glycosidic bonds.

Advanced and Supplemental Topics

The Gastrointestinal Immune System The lumen of the gastrointestinal tract is outside of the body and much of it is heavily populated with potentially pathogenic microorganisms. It is thus important that the immune system establish and maintain a strong presence at this mucosal boundary, and indeed, the digestive tube is heavily laden with lymphocytes, macrophages and other cells that participate in immune responses. Aside from all of its other functions, the gastrointestinal tract is a lymphoid organ, and the lymphoid tissue within it is collectively referred to as the gut-associated lymphoid tissue or GALT. The number of lymphocytes in the GALT is roughly equivalent to those in the spleen, and, based on location, these cells are distributed in three basic populations: Peyer's Patches: These are lymphoid follicles similar in many ways to lymph nodes, located in the mucosa and extending into the submucosa of the small intestine, especially the ileum. In adults, B lymphocytes predominate in Peyer's patches. Smaller lymphoid nodules can be found throughout the intestinal tract. In the image of canine ileum below, three lymphoid follicles of a Peyer's patch can be seen. The muscularis is at the top left, and mucosal epithelium in the bottom right.

Lamina propria lymphocytes: These are lymphocytes scattered in the lamina propria of the mucosa. A majority of these cells are IgA-secreting B cells.

Intraepithelial lymphocytes: These are lymphcytes that are positioned in the basolateral spaces between lumenal epithelial cells, beneath the tight junctions (they are "inside" the epithelium, but not inside epithelial cells as the name may incorrectly suggest). Another important component of the GI immune system is the M or microfold cell. M cells are a specific cell type in the intestinal epithelium over lymphoid follicles that endocytose a variety of protein and peptide antigens. Instead of digesting these proteins, M cells transport them into the underlying tissue, where they are taken up by local dendritic cells and macrophages. Dendritic cells and macrophages that receive antigens from M cells present them to T cells in the GALT, leading ultimately to appearance of immunoglobulin A-secreting plasma cells in the mucosa. Dendritic cells below the epithelium can also sample lumenal antigens by pushing pseudopods between epithelial cells. The secretory IgA is transported through the epithelial cells into the lumen, where, for example, it interferes with adhesion and invasion of bacteria. T cells exposed to antigen in Peyer's patches also migrate into the lamina propria and the epithelium, where they mature to cytotoxic T cells, providing another mechanism for containing microbial assaults. In addition to the GALT discussed above, lymph nodes that receive lymph draining from the gut (mesenteric nodes) and Kupffer cells (phagocytic cells in the liver) play important roles in protecting the body against invasion.

Dietary Polysaccharides: Structure and Digestion

Polysaccharides, particularly of plant origin, are prominent components in the diets are herbivores and omnivores. This complex set of molecules has been categorized in several ways, depending on whether the focus is chemistry or nutrition. From the standpoint of digestive physiology and nutrition, perhaps the most relevant classification is based on whether or not animals synthesize enzymes that allow the polysaccharide in question to be digested into absorbable monosaccharides. In this view, we have starch, which can be digested by vertebrate enzymes,

versus fiber, which cannot.

Starch: Amylose and Amylopectin

Starch is the principle carbohydrate found in plant seeds and tubers; important sources of starch include maize (corn), potato and rice. Starch exists in the form of granules, each of which consist of several million amylopectin molecules together with an even larger number of amylose molecules. Since amylopectin is a much larger molecule than amylose, the mass of amylopectin is typically 4 to 5 times that of amylose in starch. Amylose consists of a linear, helical chains of roughly 500 to 20,000 alpha-D-glucose monomers linked together through alpha (1-4) glycosidic bonds.

Amylopectin molecules are huge, branched polymers of glucose, each containing between one and two million residues. In contract to amylose, amylopectin is branched. It contains numerous amylose-like chains of up to 30 glucose residues linked through alpha (1-4) bonds, connected to one another through alpha (1-6) branch points.

The Human Eye

The human eye is wrapped in three layers of tissue: the sclerotic coat This tough layer creates the "white" of the eye except in the front where it forms the transparent cornea. The cornea o admits light to the interior of the eye and o bends the light rays to that they can be brought to a focus.

The surface of the cornea is kept moist and dust-free by secretions from the tear glands.

the choroid coat This middle layer is deeply pigmented with melanin. It reduces reflection of stray light within the eye. The choroid coat forms the iris in the front of the eye. This, too, is pigmented and is responsible for eye "color". The size of its opening, the pupil, is variable and under the control of the autonomic nervous system. In dim light (or when danger threatens), the pupil opens wider letting more light into the eye. In bright light the pupil closes down. This not only reduces the amount of light entering the eye but also improves its image-forming ability (as does "stopping down" the iris diaphragm of a camera). the retina The retina is the inner layer of the eye. It contains the light receptors, the rods and cones (and thus serves as the "film" of the eye). The retina also has many interneurons that process the signals arising in the rods and cones before passing them back to the brain. (Note: the rods and cones are not at the surface of the retina but lie underneath the layer of interneurons.)

The blind spot

All the nerve impulses generated in the retina travel back to the brain by way of the axons in the optic nerve (above). At the point on the retina where the approximately 1 million axons converge on the optic nerve, there are no rods or cones. This spot, called the blind spot, is thus insensitive to light.

You can demonstrate the presence of the blind spot. Cover your right eye with your hand and stare at the red circle as you move closer to the screen (the square will disappear). Or cover your left eye and stare at the red square as you move.

The lens
The lens is located just behind the iris. It is held in position by zonules extending from an encircling ring of muscle. When this ciliary muscle is relaxed, its diameter increases, the zonules are put under tension, and the lens is flattened; contracted, its diameter is reduced, the zonules relax, and the lens becomes more spherical. These changes enable the eye to adjust its focus between far objects and near objects.

Farsightedness. If the eyeball is too short or the lens too flat or inflexible, the light rays entering the eye particularly those from nearby objects will not be brought to a focus by the time they strike the retina. Eyeglasses with convex lenses can correct the problem. Farsightedness is called hypermetropia. Nearsightedness. If the eyeball is too long or the lens too spherical, the image of distant objects is brought to a focus in front of the retina and is out of focus again before the light strikes the retina. Nearby objects can be seen more easily. Eyeglasses with concave lenses correct this problem by diverging the light rays before they enter the eye. Nearsightedness is called myopia.

Cataracts One or both lenses often become cloudy as one ages. When a cataract seriously interferes with seeing, the cloudy lens is easily removed and a plastic one substituted. The entire process can be done in a few minutes as an outpatient under local anesthesia.

The iris and lens divide the eye into two main chambers:

the front chamber is filled with a watery liquid, the aqueous humor. the rear chamber is filled with a jellylike material, the vitreous body.

[back up to figure]

The Retina
Four kinds of light-sensitive receptors are found in the retina: rods three kinds of cones, each "tuned" to absorb light from a portion of the spectrum of visible light o cones that absorb longwavelength light (red) o cones that absorb middlewavelength light (green) o cones that absorb shortwavelength light (blue)

This scanning electron micrograph (courtesy of Scott Mittman and David R. Copenhagen) shows rods and cones in the retina of the tiger salamander. Each type of receptor has its own special pigment for absorbing light. Each consists of:

a transmembrane protein called opsin coupled to the prosthetic group retinal. Retinal is a derivative of vitamin A (which explains why night blindness is one sign of vitamin A deficiency) and is used by all four types of receptors.

The amino acid sequence of each of the four types of opsin are similar, but the differences account for their differences in absorption spectrum. The retina also contains a complex array of interneurons:

bipolar cells and ganglion cells that together form a path from the rods and cones to the brain a complex array of other interneurons that form synapses with the bipolar and ganglion cells and modify their activity.

Ganglion cells are always active. Even in the dark they generate trains of action potentials and conduct them back to the brain along the optic nerve. Vision is based on the modulation of these nerve impulses. There is not the direct relationship between visual stimulus and an action potential that is found in the senses of hearing, taste, and smell. In fact, action potentials are not even generated in the rods and cones.

Rod Vision
Rhodopsin is the light-absorbing pigment of the rods. It is incorporated in the membranes of disks that are neatly stacked (some 2000 of them) in the outer portion of the rod. (This arrangement is reminiscent of the organization of thylakoids, another light-absorbing device.)

The electron micrograph (courtesy of Keith Porter) shows the rod cells of the kangaroo rat. The outer segments of the rods contain the orderly stacks of membranes which incorporate rhodopsin. The inner portion contain many mitochondria. The two parts of the rod are connected

by a stalk (arrow) that has the same structure as a primary cilium. Although the disks are initially formed from the plasma membrane, they become separated from it. Thus signals generated in the disks must be transmitted by a chemical mediator (a "second messenger" called cyclic GMP (cGMP) to alter the potential of the plasma membrane of the rod. Rhodopsin consists of an opsin of 348 amino acids coupled to retinal. The opsin has 7 segments of alpha helix that pass back and forth through the lipid bilayer of the disk membrane.

Retinal consists of a system of alternating single and double bonds. In the dark, the hydrogen atoms attached to the #11 and #12 carbon atoms of retinal (red arrows) point in the same direction producing a kink in the molecule. This configuration is designated cis. When light is absorbed by retinal, the molecule straightens out forming the alltrans isomer. This physical change in retinal triggers the following chain of events culminating in a change in the pattern of impulses sent back along the optic nerve.
1. Formation of all- trans retinal activates its opsin. 2. Activated rhodopsin, in turn, activates many molecules of a protein complex called transducin. (Transducin is one of many types of G-protein-coupled receptors GPCRs.) 3. Transducin activates an enzyme that breaks down cyclic GMP. (GMP is the guanine-containing cousin of AMP.) 4. The drop in cGMP closes Na+ and Ca2+ channels in the plasma membrane of the rod. Because these positive ions can no longer enter (while Ca2+ can still leave), the interior of the cell becomes more negative (hyperpolarized) increasing its membrane potential from -40 to as much as -80 mV. 5. This slows the release of a neurotransmitter at the synapse of the rod. However, because this transmitter is inhibitory, the effect is a "double-negative" one, i.e. positive. 6. Interneurons are relieved of their normal inhibition. This, in turn, relieves the inhibition of the spontaneous firing of the ganglion cells to which they are connected.

So the retina is not simply a sheet of photocells, but a tiny brain center that carries out complex information processing before sending signals back along the optic nerve. In fact, the retina really is part of the brain and grows out from it during embryonic development.
Rod vision is acute but coarse.

Rods do not provide a sharp image for several reasons. adjacent rods are connected by gap junctions and so share their changes in membrane potential several nearby rods often share a single circuit to one ganglion cell a single rod can send signals to several different ganglion cells. So if only a single rod is stimulated, the brain has no way of determining exactly where on the retina it was.

However, rods are extremely sensitive to light. A single photon (the minimum unit of light) absorbed by a small cluster of adjacent rods is sufficient to send a signal to the brain. So although rods provide us with a relatively grainy, colorless image, they permit us to detect light that is over a billion times dimmer than what we see on a bright sunny day.

Cone Vision
Although cones operate only in relatively bright light, they provide us with our sharpest images and enable us to see colors. Most of the 3 million cones in each retina are confined to a small region just opposite the lens called the fovea. So our sharpest and colorful images are limited to a small area of view. Because we can quickly direct our eyes to anything in view that interests us, we tend not to be aware of just how poor our peripheral vision is. The three types of cones provide us the basis of color vision. Cones are "tuned" to different portions of the visible spectrum.

red absorbing cones; those that absorb best at the relatively long wavelengths peaking at 565 nm green absorbing cones with a peak absorption at 535 nm blue absorbing cones with a peak absorption at 440 nm.

Retinal is the prosthetic group for each pigment. Differences in the amino acid sequence of their opsins accounts for the differences in absorption.

The response of cones is not all-or-none. Light of a given wavelength (color), say 500 nm (green), stimulates all three types of cones, but the greenabsorbing cones will be stimulated most strongly. Like rods, the absorption of light does not trigger action potentials but modulates the membrane potential of the cones.

Color

Blindness
The term color blindness is something of a misnomer. Very few (~1 in 105) people cannot distinguish colors at all. Most "color-blind" people actually have abnormal color vision such as confusing the red and green of traffic lights. As high as 8% of the males in some populations have an inherited defect in their ability to discriminate reds and greens. These defects are found almost exclusively in males because the genes that encode the redabsorbing and green-absorbing opsins are on the X chromosome. [Discussion of Xlinkage]

The X chromosome normally carries a cluster of from 2 to 9 opsin genes. The minimum basis for normal redgreen vision is one gene that absorbs efficiently in the red and one that absorbs well in the green (chromosome 1 in the figure). Multiple copies of these genes are also fine (2 and 3). Males with either a "green gene" or "red gene" missing are severely color blind (4 and 5). However, if all the red genes carry mutations (this seldom seems to be the case for the green genes nobody knows why), then they may have red-green color blindness that ranges from mild to severe depending on the particular mutations involved (6). The rule seems to be that the more the mutations shift the pigment towards green, the more serious the defect. However, a large number of mutations doesn't always produce serious defects. Multiple mutations in a single gene may offset each other producing only mild defects. And as long as one normal copy of each gene is present, the presence of additional mutated genes seldom produce a serious problem (7). Why do some males have as many as 9 copies of genes encoding the red and green opsins, when two are enough? The sequences of the red and green genes are the same at 98% of their nucleotides. This high degree of similarity creates the risk of mismatches in synapsis during meiosis with unequal crossing over. [Click for an example]
Blue vision

Abnormal blue sensitivity occasionally occurs in humans but is much rarer than abnormalities in red-

green vision. The gene for the blue-cone opsin is located on chromosome 7. Thus this trait shows an autosomal pattern of inheritance being found in females as often as in males. Starch is digested to glucose in two basic steps: First amylose and amylopectin are hydrolyzed into small fragments through the action of alpha-amylase, secreted by salivary glands in some species, and from the pancreas in all. Amylase cleaves only internal alpha (1-4) glycosidic bonds, thereby reducing starch to three different oligosaccharides: maltose (disaccharide), maltotriose (trisaccharide), and a group of alpha-limit dextrins which contain branch points from amylopectin.

Second, maltose, maltotriose and limit dextrins are hydrolyzed on the lumenal surface of the small intestine by a brush border enzyme complex called sucrase-isomaltase (also often referred to as maltase). This step ultimately yields glucose monomers that are then transported into the small intestinal enterocyte by co-transport with sodium ions.
Dietary Fiber: Cellulose and Hemicellulose

Several definitions have been proposed for "fiber". An early definition, still quite appropriate, basically states that fiber is the portion of food derived from

plant cell walls that is poorly digested by mammals." To put it another way, mammals often consume fiber, but do not themselves secrete the enzymes necessary to digest it into a form that can be absorbed. Another common definition for fiber is the non-starch polysaccharide component of foodstuffs. The chief components of dietary fiber are cellulose and hemicellulose, both of plant origin. Pectin and pectic acid are other plant polysaccharides often present in diets. Cellulose is a linear polymer of between 1000 and 10,000 beta-D-glucose molecules in which adjacent glucose molecules are joined covalently through beta (1-4) glycosidic bonds. The beta (1-4) bonds cause the polymer to assume a non-helical, straight structure, which is different from the helical structure imposed on starch molecules by the alpha (1-4) bonding. The nonhelical structure of cellulose also promotes hydrogen bonding between cellulose molecules. Cellulose polymers associate with one another through a huge number of hydrogen bonds to form microfibers. Microfibers interact to form cellulose fibers. A typical fiber contains roughly 500,000 cellulose molecules. The high tensile strength of cellulose fibers reflects the massive number of hydrogen bonds involved in its structure. Hemicellulose is a heteropolymer composed of a variety of sugars, including xylose, arabinose and

mannose in a branched structure. In contrast to the highly ordered structure of cellulose, hemicellulose assumes an amorphose structure and becomes highly hydrated to form a gel. No vertebrate cell has been identified that produces an enzyme that hydrolyzes celluloses or hemicelluloses. Certainly, amylase will not cleave these two polysaccharides. Dietary fiber therefore is indigestable and passes through the small intestine essentially unchanged. Within the large intestine (or the forestomaches of ruminants), fiber is digested by enzymes - cellulases and hemecellulases - of microbial origin, a process refered to as fermentation. Fermentation does not yield monosaccharides that can be absorbed. Rather, its chief products are short chain volatile fatty acids, which are readily absorbed and utilized for energy and lipid synthesis. Thus, if the fermentation vat is of sufficient size (i.e. herbivores), dietary fiber can be a major source of energy.