24 Chapter 24: Nutrient Transport and Gas Exchange

Joshua Reid and Mason Tedeschi

Learning Objectives

By the end of this section, students should be able to:

24.1 Contrast the major functions of roots, stems, xylem, phloem, leaves, reproductive structures, and stomata in plants.

24.2 Be able to describe how capillary action, cohesion, and transpiration contribute to water uptake and transport in plants.

24.3 Be able to trace the path of a blood cell as it carries gases to and from the body.

24.4 How are multiple organ systems involved in the process of animal cellular respiration?

24.5 Be able to describe the process of gas exchange in plants and animals, and the role of oxygen, carbon dioxide, and hemoglobin in this process.

Animals: Circulation

In all animals, except a few simple types, the circulatory system is used to transport nutrients and gases through the body. Simple diffusion allows some water, nutrient, waste, and gas exchange into primitive animals that are only a few cell layers thick; however, bulk flow is the only method by which the entire body of larger more complex organisms is accessed.

Circulatory System Architecture

The circulatory system is effectively a network of cylindrical vessels: the arteries, veins, and capillaries that emanate from a pump, the heart. In all vertebrate organisms, as well as some invertebrates, this is a closed-loop system, in which the blood is not free in a cavity. In a closed circulatory system, blood is contained inside blood vessels and circulates unidirectionally from the heart around the systemic circulatory route, then returns to the heart again, as illustrated in Figure 22.1 a. As opposed to a closed system, arthropods—including insects, crustaceans, and most mollusks—have an open circulatory system, as illustrated in Figure 22.1 b. In an open circulatory system, the blood is not enclosed in the blood vessels but is pumped into a cavity called a hemocoel and is called hemolymph because the blood mixes with the interstitial fluid. As the heart beats and the animal moves, the hemolymph circulates around the organs within the body cavity and then reenters the hearts through openings called ostia. This movement allows for gas and nutrient exchange. An open circulatory system does not use as much energy as a closed system to operate or to maintain; however, there is a trade-off with the amount of blood that can be moved to metabolically active organs and tissues that require high levels of oxygen. In fact, one reason that insects with wing spans of up to two feet wide (70 cm) are not around today is probably because they were outcompeted by the arrival of birds 150 million years ago. Birds, having a closed circulatory system, are thought to have moved more agilely, allowing them to get food faster and possibly to prey on the insects.


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Figure 22.1 In (a) closed circulatory systems, the heart pumps blood through vessels that are separate from the interstitial fluid of the body. Most vertebrates and some invertebrates, like this annelid earthworm, have a closed circulatory system. In (b) open circulatory systems, a fluid called hemolymph is pumped through a blood vessel that empties into the body cavity. Hemolymph returns to the blood vessel through openings called ostia. Arthropods like this bee and most mollusks have open circulatory systems.

Reading Question #1

All of the following have blood vessels except:

A. Birds

B. Humans

C. Fish

D. Crabs

Circulatory System Variation in Animals

The circulatory system varies from simple systems in invertebrates to more complex systems in vertebrates. The simplest animals, such as the sponges (Porifera) and rotifers (Rotifera), do not need a circulatory system because diffusion allows adequate exchange of water, nutrients, and waste, as well as dissolved gases, as shown in Figure 22.2 a. Organisms that are more complex but still only have two layers of cells in their body plan, such as jellies (Cnidaria) and comb jellies (Ctenophora) also use diffusion through their epidermis and internally through the gastrovascular compartment. Both their internal and external tissues are bathed in an aqueous environment and exchange fluids by diffusion on both sides, as illustrated in Figure 22.2 b. Exchange of fluids is assisted by the pulsing of the jellyfish body.


Figure 22.2 Simple animals consisting of a single cell layer such as the (a) sponge or only a few cell layers such as the (b) jellyfish do not have a circulatory system. Instead, gases, nutrients, and wastes are exchanged by diffusion.

For more complex organisms, diffusion is not efficient for cycling gases, nutrients, and waste effectively through the body; therefore, more complex circulatory systems evolved. Most arthropods and many mollusks have open circulatory systems. In an open system, an elongated beating heart pushes the hemolymph through the body and muscle contractions help to move fluids. The larger more complex crustaceans, including lobsters, have developed arterial-like vessels to push blood through their bodies, and the most active mollusks, such as squids, have evolved a closed circulatory system and are able to move rapidly to catch prey. Closed circulatory systems are a characteristic of vertebrates; however, there are significant differences in the structure of the heart and the circulation of blood between the different vertebrate groups due to adaptation during evolution and associated differences in anatomy. Figure 22.3 illustrates the basic circulatory systems of some vertebrates: fish, amphibians, reptiles, and mammals.


Figure 22.3 (a) Fish have the simplest circulatory systems of the vertebrates: blood flows unidirectionally from the two-chambered heart through the gills and then the rest of the body. (b) Amphibians have two circulatory routes: one for oxygenation of the blood through the lungs and skin, and the other to take oxygen to the rest of the body. The blood is pumped from a three-chambered heart with two atria and a single ventricle. (c) Reptiles also have two circulatory routes; however, blood is only oxygenated through the lungs. The heart is three chambered, but the ventricles are partially separated so some mixing of oxygenated and deoxygenated blood occurs except in crocodilians and birds. (d) Mammals and birds have the most efficient heart with four chambers that completely separate the oxygenated and deoxygenated blood; it pumps only oxygenated blood through the body and deoxygenated blood to the lungs.


As illustrated in Figure 22.3 a. Fish have a single circuit for blood flow and a two-chambered heart that has only a single atrium and a single ventricle. The atrium collects blood that has returned from the body and the ventricle pumps the blood to the gills where gas exchange occurs and the blood is re-oxygenated; this is called gill circulation. The blood then continues through the rest of the body before arriving back at the atrium; this is called systemic circulation. This unidirectional flow of blood produces a gradient of oxygenated to deoxygenated blood around the fish’s systemic circuit. The result is a limit in the amount of oxygen that can reach some of the organs and tissues of the body, reducing the overall metabolic capacity of fish.

In amphibians, reptiles, birds, and mammals, blood flow is directed in two circuits: one through the lungs and back to the heart, which is called pulmonary circulation, and the other throughout the rest of the body and its organs including the brain (systemic circulation). In amphibians, gas exchange also occurs through the skin during pulmonary circulation and is referred to as pulmocutaneous circulation.

As shown in Figure 22.3  b, amphibians have a three-chambered heart that has two atria and one ventricle rather than the two-chambered heart of fish. The two atria (superior heart chambers) receive blood from the two different circuits (the lungs and the systems), and then there is some mixing of the blood in the heart’s ventricle (inferior heart chamber), which reduces the efficiency of oxygenation. The advantage to this arrangement is that high pressure in the vessels pushes blood to the lungs and body. The mixing is mitigated by a ridge within the ventricle that diverts oxygen-rich blood through the systemic circulatory system and deoxygenated blood to the pulmocutaneous circuit. For this reason, amphibians are often described as having double circulation.

Most reptiles also have a three-chambered heart similar to the amphibian heart that directs blood to the pulmonary and systemic circuits, as shown in Figure 22.3 c. The ventricle is divided more effectively by a partial septum, which results in less mixing of oxygenated and deoxygenated blood. Some reptiles (alligators and crocodiles) are the most primitive animals to exhibit a four-chambered heart. Crocodilians have a unique circulatory mechanism where the heart shunts blood from the lungs toward the stomach and other organs during long periods of submergence, for instance, while the animal waits for prey or stays underwater waiting for prey to rot. One adaptation includes two main arteries that leave the same part of the heart: one takes blood to the lungs and the other provides an alternate route to the stomach and other parts of the body. Two other adaptations include a hole in the heart between the two ventricles, called the foramen of Panizza, which allows blood to move from one side of the heart to the other, and specialized connective tissue that slows the blood flow to the lungs. Together these adaptations have made crocodiles and alligators one of the most evolutionarily successful animal groups on earth.

In mammals and birds, the heart is also divided into four chambers: two atria and two ventricles, as illustrated in Figure 22.3 d. The oxygenated blood is separated from the deoxygenated blood, which improves the efficiency of double circulation and is probably required for the warm-blooded lifestyle of mammals and birds. The four-chambered heart of birds and mammals evolved independently from a three-chambered heart. The independent evolution of the same or a similar biological trait is referred to as convergent evolution.

Osmosis is the diffusion of water across a membrane in response to osmotic pressure caused by an imbalance of molecules on either side of the membrane. Osmoregulation is the process of maintenance of salt and water balance (osmotic balance) across membranes within the body’s fluids, which are composed of water, plus electrolytes and non-electrolytes. An electrolyte is a solute that dissociates into ions when dissolved in water. A non-electrolyte, in contrast, doesn’t dissociate into ions during water dissolution. Both electrolytes and non-electrolytes contribute to the osmotic balance. The body’s fluids include blood plasma, the cytosol within cells, and interstitial fluid, the fluid that exists in the spaces between cells and tissues of the body. The membranes of the body (such as the pleural, serous, and cell membranes) are semi-permeable membranes. Semi-permeable membranes are permeable (or permissive) to certain types of solutes and water. Solutions on two sides of a semi-permeable membrane tend to equalize in solute concentration by movement of solutes and/or water across the membrane. As seen in Figure 22.4, a cell placed in water tends to swell due to gain of water from the hypotonic or “low salt” environment. A cell placed in a solution with higher salt concentration, on the other hand, tends to make the membrane shrivel up due to loss of water into the hypertonic or “high salt” environment. Isotonic cells have an equal concentration of solutes inside and outside the cell; this equalizes the osmotic pressure on either side of the cell membrane which is a semi-permeable membrane.


Figure 22.4 Cells placed in a hypertonic environment tend to shrink due to loss of water. In a hypotonic environment, cells tend to swell due to intake of water. The blood maintains an isotonic environment so that cells neither shrink nor swell. (credit: Mariana Ruiz Villareal)

The body does not exist in isolation. There is a constant input of water and electrolytes into the system. While osmoregulation is achieved across membranes within the body, excess electrolytes and wastes are transported to the kidneys and excreted, helping to maintain osmotic balance.


Reading Question #2

Osmoregulation is the process of maintaining the balance of:

A. Water and electrolytes only

B. Water, electrolytes, and non-electrolytes

C. Water and non-electrolytes only

D. Water only

Need for Osmoregulation

Biological systems constantly interact and exchange water and nutrients with the environment by way of consumption of food and water and through excretion in the form of sweat, urine, and feces. Without a mechanism to regulate osmotic pressure, or when a disease damages this mechanism, there is a tendency to accumulate toxic waste and water, which can have dire consequences.

Mammalian systems have evolved to regulate not only the overall osmotic pressure across membranes, but also specific concentrations of important electrolytes in the three major fluid compartments: blood plasma, extracellular fluid, and intracellular fluid. Since osmotic pressure is regulated by the movement of water across membranes, the volume of the fluid compartments can also change temporarily. Because blood plasma is one of the fluid components, osmotic pressures have a direct bearing on blood pressure.

Osmoregulators and Osmoconformers

Persons lost at sea without any freshwater to drink are at risk of severe dehydration because the human body cannot adapt to drinking seawater, which is hypertonic in comparison to body fluids. Organisms such as goldfish that can tolerate only a relatively narrow range of salinity are referred to as stenohaline. About 90 percent of all bony fish are restricted to either freshwater or seawater. They are incapable of osmotic regulation in the opposite environment. It is possible, however, for a few fishes like salmon to spend part of their life in freshwater and part in seawater. Organisms like the salmon and molly that can tolerate a relatively wide range of salinity are referred to as euryhaline organisms. This is possible because some fish have evolved osmoregulatory mechanisms to survive in all kinds of aquatic environments. When they live in freshwater, their bodies tend to take up water because the environment is relatively hypotonic, as illustrated in Figure 22.5 a. In such hypotonic environments, these fish do not drink much water. Instead, they pass a lot of very dilute urine, and they achieve electrolyte balance by active transport of salts through the gills. When they move to a hypertonic marine environment, these fish start drinking seawater; they excrete the excess salts through their gills and their urine, as illustrated in Figure 22.5  b. Most marine invertebrates, on the other hand, may be isotonic with seawater (osmoconformers). Their body fluid concentrations conform to changes in seawater concentration. Cartilaginous fishes’ salt composition of the blood is similar to bony fishes; however, the blood of sharks contains the organic compounds urea and trimethylamine oxide (TMAO). This does not mean that their electrolyte composition is similar to that of seawater. They achieve isotonicity with the sea by storing large concentrations of urea. These animals that secrete urea are called ureotelic animals. TMAO stabilizes proteins in the presence of high urea levels, preventing the disruption of peptide bonds that would occur in other animals exposed to similar levels of urea. Sharks are cartilaginous fish with a rectal gland to secrete salt and assist in osmoregulation.


Figure 22.5 Fish are osmoregulators, but must use different mechanisms to survive in (a) freshwater or (b) saltwater environments. (credit: modification of work by Duane Raver, NOAA)

Plants: Water Transport

Plant Organ Systems

In plants, just as in animals, similar cells working together form a tissue. When different types of tissues work together to perform a unique function, they form an organ; organs working together form organ systems. Vascular plants have two distinct organ systems: a shoot system, and a root system. The shoot system consists of two portions: the vegetative (non-reproductive) parts of the plant, such as the leaves and the stems, and the reproductive parts of the plant, which include flowers and fruits. The shoot system generally grows above ground, where it absorbs the light needed for photosynthesis. The root system, which supports the plants and absorbs water and minerals, is usually underground. Figure 22.6 shows the organ systems of a typical plant.


Figure 22.6 The shoot system of a plant consists of leaves, stems, flowers, and fruits. The root system anchors the plant while absorbing water and minerals from the soil.

Plant Tissues

Plants are multicellular eukaryotes with tissue systems made of various cell types that carry out specific functions.

Dermal tissue, for example, is a simple tissue that covers the outer surface of the plant and controls gas exchange. Vascular tissue is an example of a complex tissue, and is made of two specialized conducting tissues: xylem and phloem. Xylem tissue transports water and nutrients from the roots to different parts of the plant, and includes three different cell types: vessel elements and tracheids (both of which conduct water), and xylem parenchyma. Phloem tissue, which transports organic compounds from the site of photosynthesis to other parts of the plant, consists of four different cell types: sieve cells (which conduct photosynthates), companion cells, phloem parenchyma, and phloem fibers. Unlike xylem conducting cells, phloem conducting cells are alive at maturity. The xylem and phloem always lie adjacent to each other (Figure 22.7). In stems, the xylem and the phloem form a structure called a vascular bundle; in roots, this is termed the vascular stele or vascular cylinder.


Figure 22.7 This light micrograph shows a cross section of a squash (Curcurbita maxima) root. Each teardrop-shaped vascular bundle consists of large xylem vessels toward the inside and smaller phloem cells toward the outside. Xylem cells, which transport water and nutrients from the roots to the rest of the plant, are dead at functional maturity. Phloem cells, which transport sugars and other organic compounds from photosynthetic tissue to the rest of the plant, are living. The vascular bundles are encased in ground tissue and surrounded by dermal tissue. (credit: modification of work by “(biophotos)”/Flickr; scale-bar data from Matt Russell)

Reading Question #3

Xylem tissue:

A. Transports water and nutrients from the roots to other parts of the plant

B. Transports sugar from the site of photosynthesis to other parts of the plant

C. Transports fertilizer from the roots to other parts of the plant

D. Transports organic compounds from the site of photosynthesis to other parts of the plant

Reading Question #4

Phloem tissue:

A. Transports water and nutrients from the roots to other parts of the plant

B. Transports sugar from the site of photosynthesis to other parts of the plant

C. Transports fertilizer from the roots to other parts of the plant

D. Transports organic compounds from the site of photosynthesis to other parts of the plant

Stems and Plant Vascular Tissue

The stem of the plant connects the roots to the leaves, helping to transport absorbed water and minerals to different parts of the plant. It also helps to transport the products of photosynthesis, namely sugars, from the leaves to the rest of the plant.

The stem and other plant organs arise from the ground tissue, and are primarily made up of simple tissues formed from three types of cells: parenchyma, collenchyma, and sclerenchyma cells.

Parenchyma cells are the most common plant cells (Figure 22.8). They are found in the stem, the root, the inside of the leaf, and the pulp of the fruit. Parenchyma cells are responsible for metabolic functions, such as photosynthesis, and they help repair and heal wounds. Some parenchyma cells also store starch.


Figure 22.8 The stem of common St John’s Wort (Hypericum perforatum) is shown in cross section in this light micrograph. The central pith (greenish-blue, in the center) and peripheral cortex (narrow zone 3–5 cells thick just inside the epidermis) are composed of parenchyma cells. Vascular tissue composed of xylem (red) and phloem tissue (green, between the xylem and cortex) surrounds the pith. (credit: Rolf-Dieter Mueller)

The xylem and phloem that make up the vascular tissue of the stem are arranged in distinct strands called vascular bundles, which run up and down the length of the stem. When the stem is viewed in cross section, the vascular bundles of dicot stems are arranged in a ring. In plants with stems that live for more than one year, the individual bundles grow together and produce the characteristic growth rings. In monocot stems, the vascular bundles are randomly scattered throughout the ground tissue.

(Figure 22.9).

Figure 22.9 In (a) dicot stems, vascular bundles are arranged around the periphery of the ground tissue. The xylem tissue is located toward the interior of the vascular bundle, and phloem is located toward the exterior. Sclerenchyma fibers cap the vascular bundles. In (b) monocot stems, vascular bundles composed of xylem and phloem tissues are scattered throughout the ground tissue.

Xylem tissue has three types of cells: xylem parenchyma, tracheids, and vessel elements. The latter two types conduct water and are dead at maturity. Tracheids are xylem cells with thick secondary cell walls that are lignified. Water moves from one tracheid to another through regions on the side walls known as pits, where secondary walls are absent. Vessel elements are xylem cells with thinner walls; they are shorter than tracheids. Each vessel element is connected to the next by means of a perforation plate at the end walls of the element. Water moves through the perforation plates to travel up the plant.

Phloem tissue is composed of sieve-tube cells, companion cells, phloem parenchyma, and phloem fibers. A series of sieve-tube cells (also called sieve-tube elements) are arranged end to end to make up a long sieve tube, which transports organic substances such as sugars and amino acids. The sugars flow from one sieve-tube cell to the next through perforated sieve plates, which are found at the end junctions between two cells. Although still alive at maturity, the nucleus and other cell components of the sieve-tube cells have disintegrated. Companion cells are found alongside the sieve-tube cells, providing them with metabolic support. The companion cells contain more ribosomes and mitochondria than the sieve-tube cells, which lack some cellular organelles.


Reading Question #5

The main difference between dicot and monocot stems is:

A. Dicot stems have a dual structure

B. Dicot stems have vascular bundles around the periphery of the ground tissue, while monocots have vascular bundles distributed throughout

C. Monocot stems only have xylem tissue and not phloem tissue

D. Monocots don’t have vascular tissue


Growth in Stems

Growth in plants occurs as the stems and roots lengthen. Some plants, especially those that are woody, also increase in thickness during their lifespan. The increase in length of the shoot and the root is referred to as primary growth, and is the result of cell division in the shoot apical meristem. Secondary growth is characterized by an increase in thickness or girth of the plant, and is caused by cell division in the lateral meristem. Figure 22.10 shows the areas of primary and secondary growth in a plant. Herbaceous plants mostly undergo primary growth, with hardly any secondary growth or increase in thickness. Secondary growth or “wood” is noticeable in woody plants; it occurs in some dicots, but occurs very rarely in monocots.


Figure 22.10 In woody plants, primary growth is followed by secondary growth, which allows the plant stem to increase in thickness or girth. Secondary vascular tissue is added as the plant grows, as well as a cork layer. The bark of a tree extends from the vascular cambium to the epidermis.

Water Transport

Figure 22.11 With heights nearing 116 meters, (a) coastal redwoods (Sequoia sempervirens) are the tallest trees in the world. Plant roots can easily generate enough force to (b) buckle and break concrete sidewalks, much to the dismay of homeowners and city maintenance departments. (credit a: modification of work by Bernt Rostad; credit b: modification of work by Pedestrians Educating Drivers on Safety, Inc.)

Movement of Water and Minerals in the Xylem

Solutes, pressure, and gravity are all important for the transport of water in plants. Transpiration is the loss of water from the plant through evaporation at the leaf surface. It is the main driver of water movement in the xylem. Transpiration is caused by the evaporation of water at the leaf–atmosphere interface. Water from the roots is pulled up by this tension. At night, when stomata shut and transpiration stops, the water is held in the stem and leaf by the adhesion of water to the cell walls of the xylem vessels and tracheids, and the cohesion of water molecules to each other. This is called the cohesion–tension theory of sap ascent.

Inside the leaf at the cellular level, water on the surface of mesophyll cells saturates the cellulose microfibrils of the primary cell wall. The leaf contains many large intercellular air spaces for the exchange of oxygen for carbon dioxide, which is required for photosynthesis. The wet cell wall is exposed to this leaf internal air space, and the water on the surface of the cells evaporates into the air spaces, decreasing the thin film on the surface of the mesophyll cells. This decrease creates a greater tension on the water in the mesophyll cells (Figure 22.12), thereby increasing the pull on the water in the xylem vessels. The xylem vessels and tracheids are structurally adapted to cope with large changes in pressure. Rings in the vessels maintain their tubular shape, much like the rings on a vacuum cleaner hose keep the hose open while it is under pressure. Small perforations between vessel elements reduce the number and size of gas bubbles that can form via a process called cavitation. The formation of gas bubbles in xylem interrupts the continuous stream of water from the base to the top of the plant, causing a break termed an embolism in the flow of xylem sap. The taller the tree, the greater the tension forces needed to pull water, and the more cavitation events. In larger trees, the resulting embolisms can plug xylem vessels, making them nonfunctional.


Figure 22.12 The cohesion–tension theory of sap ascent is shown. Evaporation from the mesophyll cells produces a negative water potential gradient that causes water to move upwards from the roots through the xylem.

Transpiration—the loss of water vapor to the atmosphere through stomata—is a passive process, meaning that metabolic energy in the form of ATP is not required for water movement. The energy driving transpiration is the difference in energy between the water in the soil and the water in the atmosphere. However, transpiration is tightly controlled.

Control of Transpiration

The atmosphere to which the leaf is exposed drives transpiration, but also causes massive water loss from the plant. Up to 90 percent of the water taken up by roots may be lost through transpiration.

Leaves are covered by a waxy cuticle on the outer surface that prevents the loss of water. Regulation of transpiration, therefore, is achieved primarily through the opening and closing of stomata on the leaf surface. Stomata are surrounded by two specialized cells called guard cells, which open and close in response to environmental cues such as light intensity and quality, leaf water status, and carbon dioxide concentrations. Stomata must open to allow air containing carbon dioxide and oxygen to diffuse into the leaf for photosynthesis and respiration.


Figure 22.13 Visualized at 500x with a scanning electron microscope, several stomata are clearly visible on (a) the surface of this sumac (Rhus glabra) leaf. At 5,000x magnification, the guard cells of (b) a single stoma from lyre-leaved sand cress (Arabidopsis lyrata). In this (c) light micrograph cross-section of an A. lyrata leaf, the guard cell pair is visible along with the large, sub-stomatal air space in the leaf. (credit: modification of work by Robert R. Wise; part c scale-bar data from Matt Russell)

When stomata are open, however, water vapor is lost to the external environment, increasing the rate of transpiration. Therefore, plants must maintain a balance between efficient photosynthesis and water loss.

Plants have evolved over time to adapt to their local environment and reduce transpiration (Figure 22.14). Desert plant and plants that grow on other plants have limited access to water. Such plants usually have a much thicker waxy cuticle than those growing in more moderate, well-watered environments. Aquatic plants also have their own set of anatomical and morphological leaf adaptations.


Figure 22.14 Plants are suited to their local environment. (a) This prickly pear cactus (Opuntia sp.) and (b) this tropical Aeschynanthus perrottetii have adapted to very limited water resources. The leaves of a prickly pear are modified into spines, which lowers the surface-to-volume ratio and reduces water loss. Photosynthesis takes place in the stem, which also stores water. (b) A. perottetii leaves have a waxy cuticle that prevents water loss. (c) Goldenrod (Solidago sp.) is well suited for moderate environments. (d) This fragrant water lily (Nymphaea odorata) is adapted to thrive in aquatic environments. (credit a: modification of work by Jon Sullivan; credit b: modification of work by L. Shyamal/Wikimedia Commons; credit c: modification of work by Huw Williams; credit d: modification of work by Jason Hollinger)

Transportation of Photosynthates in the Phloem

Plants need an energy source to grow. In seeds and bulbs, food is stored in polymers (such as starch) that are converted by metabolic processes into sucrose for newly developing plants. Once green shoots and leaves are growing, plants are able to produce their own food by photosynthesizing. The products of photosynthesis are called photosynthates, which are usually in the form of simple sugars such as sucrose.

Structures that produce photosynthates for the growing plant are referred to as sources. Sugars produced in sources, such as leaves, need to be delivered to growing parts of the plant via the phloem in a process called translocation. The points of sugar delivery, such as roots, young shoots, and developing seeds, are called sinks. Seeds, tubers, and bulbs can be either a source or a sink, depending on the plant’s stage of development and the season.

The products from the source are usually translocated to the nearest sink through the phloem. For example, the highest leaves will send photosynthates upward to the growing shoot tip, whereas lower leaves will direct photosynthates downward to the roots. Intermediate leaves will send products in both directions, unlike the flow in the xylem, which is always unidirectional (soil to leaf to atmosphere). The pattern of photosynthate flow changes as the plant grows and develops. Photosynthates are directed primarily to the roots early on, to shoots and leaves during vegetative growth, and to seeds and fruits during reproductive development. They are also directed to tubers for storage.

Translocation: Transport from Source to Sink

Photosynthates, such as sucrose, are produced in the mesophyll cells of photosynthesizing leaves. From there they are translocated through the phloem to where they are used or stored. Mesophyll cells are connected by cytoplasmic channels. Photosynthates move through these channels to reach phloem sieve-tube elements (STEs) in the vascular bundles. From the mesophyll cells, the photosynthates are loaded into the phloem STEs. The sucrose is actively transported against its concentration gradient (a process requiring ATP) into the phloem cells using the electrochemical potential of the proton gradient. This is coupled to the uptake of sucrose with a carrier protein called the sucrose-H+ symporter.

Phloem STEs have reduced cytoplasmic contents, and are connected by a sieve plate with pores that allow for pressure-driven bulk flow, or translocation, of phloem sap. Companion cells are associated with STEs. They assist with metabolic activities and produce energy for the STEs (Figure 22.15).


Figure 22.15 Phloem is comprised of cells called sieve-tube elements. Phloem sap travels through perforations called sieve tube plates. Neighboring companion cells carry out metabolic functions for the sieve-tube elements and provide them with energy. Lateral sieve areas connect the sieve-tube elements to the companion cells.

Figure 22.15 Phloem is comprised of cells called sieve-tube elements. Phloem sap travels through perforations called sieve tube plates. Neighboring companion cells carry out metabolic functions for the sieve-tube elements and provide them with energy. Lateral sieve areas connect the sieve-tube elements to the companion cells.

Once in the phloem, the photosynthates are translocated to the closest sink. Phloem sap is an aqueous solution that contains up to 30 percent sugar, minerals, amino acids, and plant growth regulators. Sucrose concentration in the sink cells is lower than in the phloem STEs because the sink sucrose has been metabolized for growth, or converted to starch for storage or other polymers, such as cellulose, for structural integrity. Unloading at the sink end of the phloem tube occurs by either diffusion or active transport of sucrose molecules from an area of high concentration to one of low concentration. Water diffuses from the phloem by osmosis and is then transpired or recycled via the xylem back into the phloem sap.


Figure 22.16 Sucrose is actively transported from source cells into companion cells and then into the sieve-tube elements. This reduces the water potential, which causes water to enter the phloem from the xylem. The resulting positive pressure forces the sucrose-water mixture down toward the roots, where sucrose is unloaded. Transpiration causes water to return to the leaves through the xylem vessels.


Review of cellular respiration

Let’s think back to the metabolism unit of BIOL 1403, where we discussed cellular respiration and photosynthesis.

Cellular respiration is the process of oxidizing food molecules, like glucose, to carbon dioxide and water.

The equation of cellular respiration is: C6H12O6 + 6O2 → 6CO2 + 6H2O.

The energy released is trapped in the form of ATP for use by all the energy-consuming activities of the cell. The process occurs in two phases:

  • glycolysis, the breakdown of glucose to pyruvic acid
  • the complete oxidation of pyruvic acid to carbon dioxide and water

In eukaryotes, glycolysis occurs in the cytosol and the remaining processes take place in mitochondria.


Mitochondria are membrane-enclosed organelles distributed through the cytosol of most eukaryotic cells. Their number within the cell ranges from a few hundred to, in very active cells, thousands. Their main function is the conversion of the potential energy of food molecules into ATP.

Figure 23.1. This is a simplified schematic diagram of the mitochondrion.
Figure 23.2 This image was obtained from an electron microscope – it depicts a mitochondrion found in a bat pancreatic cell.

Mitochondria have:

  • an outer membrane that encloses the entire structure
  • an inner membrane that encloses a fluid-filled matrix
  • between the two is the intermembrane space
  • the inner membrane is elaborately folded with shelflike cristae projecting into the matrix.
  • a small number (some 5–10) circular molecules of DNA

This electron micrograph in Figure 23.2, shows a single mitochondrion from a bat pancreas cell. Note the double membrane and the way the inner membrane is folded into cristae. The dark, membrane-bounded objects above the mitochondrion are lysosomes. The number of mitochondria in a cell can increase either by their fission (e.g. following mitosis) or decrease by their fusing together. Defects in either process can produce serious, even fatal, illness.

The Outer Membrane

The outer membrane contains many complexes of integral membrane proteins that form channels through which a variety of molecules and ions move in and out of the mitochondrion.

The Inner Membrane

The inner membrane contains 5 complexes of integral membrane proteins:

  • NADH dehydrogenase (Complex I)
  • succinate dehydrogenase (Complex II)
  • cytochrome c reductase (Complex III; also known as the cytochrome b-c1 complex)
  • cytochrome c oxidase (Complex IV)
  • ATP synthase (Complex V)

The Matrix

The matrix contains a complex mixture of soluble enzymes that catalyze the respiration of pyruvic acid and other small organic molecules. Here pyruvic acid is

  • oxidized by NAD+ producing NADH + H+
  • decarboxylated producing a molecule of
    • carbon dioxide (CO2) and
    • a 2-carbon fragment of acetate bound to coenzyme A forming acetyl-CoA

The Citric Acid Cycle

This 2-carbon fragment is donated to a molecule of oxaloacetic acid. The resulting molecule of citric acid (which gives its name to the process) undergoes the series of enzymatic steps shown in the diagram. The final step regenerates a molecule of oxaloacetic acid and the cycle is ready to turn again. Note that the citric acid cycle is also referred to as Krebs cycle or the TCA (tricarboxylic acid) cycle.

Figure 23.3 A flow chart depicting the citric acid cycle, also known as Krebs cycle.

A brief summary of the cycle is as follows:

  • Each of the 3 carbon atoms present in the pyruvate that entered the mitochondrion leaves as a molecule of carbon dioxide (CO2).
  • At 4 steps, a pair of electrons (2e) is removed and transferred to NAD+ reducing it to NADH + H+.
  • At one step, a pair of electrons is removed from succinic acid and reduces the prosthetic group flavin adenine dinucleotide (FAD) to FADH2.
  • The electrons of NADH and FADH2 are transferred to the electron transport chain.

The Electron Transport Chain

The electron transport chain consists of 3 complexes of integral membrane proteins

  • the NADH dehydrogenase complex (I)
  • the cytochrome c reductase complex (III)
  • the cytochrome c oxidase complex (IV)

and two freely-diffusible molecules ubiquinone, cytochrome c, that shuttle electrons from one complex to the next.

Figure 23.4 A flow chart depicting the electron transport chain (ETC), also called the respiratory chain. This process occurs exclusively within various compartments of the mitochondrion.

The electron transport chain accomplishes:

  • The stepwise transfer of electrons from NADH (and FADH2) to oxygen molecules to form (with the aid of protons) water molecules (H2O). Cytochrome c can only transfer one electron at a time, so cytochrome c oxidase must wait until it has accumulated 4 of them before it can react with oxygen.
  • Harnessing the energy released by this transfer to the pumping of protons (H+) from the matrix to the intermembrane space.
  • Approximately 20 protons are pumped into the intermembrane space as the 4 electrons needed to reduce oxygen to water pass through the respiratory chain.
  • The gradient of protons formed across the inner membrane by this process of active transport forms a miniature battery.
  • The protons can flow back down this gradient only by reentering the matrix through ATP synthase, another complex (complex V) of 16 integral membrane proteins in the inner membrane. The process is called chemiosmosis.

Chemiosmosis in mitochondria

Figure 23.5 A schematic depicting the four protein complexes of the ETC. ATP synthase is an enzyme which utilizes the proton gradient, ultimately to produce ATP.

The energy released as electrons pass down the gradient from NADH to oxygen is harnessed by three enzyme complexes of the respiratory chain (I, III, and IV) to pump protons (H+) against their concentration gradient from the matrix of the mitochondrion into the intermembrane space.

As their concentration increases there (which is the same as saying that the pH decreases), a strong diffusion gradient is set up. The only exit for these protons is through the ATP synthase complex. As in chloroplasts, the energy released as these protons flow down their gradient is harnessed to the synthesis of ATP. The process is called chemiosmosis and is an example of facilitated diffusion. One-half of the 1997 Nobel Prize in Chemistry was awarded to Paul D. Boyer and John E. Walker for their discovery of how ATP synthase works.

Fun fact!

Why do mitochondria have their own genome?

Many of the features of the mitochondrial genetic system resemble those found in bacteria. This has strengthened the theory that mitochondria are the evolutionary descendants of a bacterium that established an endosymbiotic relationship with the ancestors of eukaryotic cells early in the history of life on earth. However, many of the genes needed for mitochondrial function have since moved to the nuclear genome. The recent sequencing of the complete genome of Rickettsia prowazekii has revealed a number of genes closely related to those found in mitochondria. Perhaps rickettsias are the closest living descendants of the endosymbionts that became the mitochondria of eukaryotes.

Now that we have reviewed the complex process of cellular respiration responsible for producing

ATP, let’s come back to the physiological aspects of cellular respiration, where the focus will be on the respiratory system.

Introducing the respiratory system

Examine the cellular respiration equation again: C6H12O6 + 6O2 → 6CO2 + 6H2O.

Recall that the production of ATP using the process of chemiosmosis in mitochondria is called oxidative phosphorylation. The overall result of these reactions is the production of ATP from the energy of the electrons removed from hydrogen atoms. These atoms were originally part of a glucose molecule. At the end of the pathway, the electrons are used to reduce an oxygen molecule to oxygen ions. The extra electrons on the oxygen attract hydrogen ions (protons) from the surrounding medium, and water is formed. Thus, oxygen is the final electron acceptor in the electron transport chain.

But how do humans obtain oxygen and what structures are involved in gas exchange? The key player is the lungs and the respiratory system, which are specifically designed for efficient gas exchange via tiny structures called the alveoli. In this section, we will explore the respiratory system in great detail to obtain a greater appreciation for this incredible organ system. In short, the lungs inspire (inspiration is also referred to as inhalation) oxygen and expire (expiration is also referred to as exhalation) carbon dioxide as a byproduct of cellular respiration. This exchange of oxygen and carbon dioxide is referred to as respiration.

Breathing is an involuntary event. How often a breath is taken and how much air is inhaled or exhaled are tightly regulated by the respiratory center in the brain. Humans, when they aren’t exerting themselves, breathe approximately 15 times per minute on average. Canines, like the dog in Figure 39.1, have a respiratory rate of about 15–30 breaths per minute. With every inhalation, air fills the lungs, and with every exhalation, air rushes back out. That air is doing more than just inflating and deflating the lungs in the chest cavity. The air contains oxygen that crosses the lung tissue, enters the bloodstream, and travels to organs and tissues. Oxygen (O2) enters the cells where it is used for metabolic reactions that produce ATP, a high-energy compound. At the same time, these reactions release carbon dioxide (CO2) as a by-product. CO2 is toxic and must be eliminated. Carbon dioxide exits the cells, enters the bloodstream, travels back to the lungs, and is expired out of the body during exhalation.

Exploring lung anatomy and function

The primary function of the respiratory system is to deliver oxygen to the cells of the body’s tissues and remove carbon dioxide, a cell waste product. The main structures of the human respiratory system are the nasal cavity, the trachea, and lungs.

All aerobic organisms require oxygen to carry out their metabolic functions. Along the evolutionary tree, different organisms have devised different means of obtaining oxygen from the surrounding atmosphere. The environment in which the animal lives greatly determines how an animal respires. The complexity of the respiratory system is correlated with the size of the organism. As animal size increases, diffusion distances increase and the ratio of surface area to volume drops. In unicellular organisms, diffusion across the cell membrane is sufficient for supplying oxygen to the cell (Figure 23.6). Diffusion is a slow, passive transport process. In order for diffusion to be a feasible means of providing oxygen to the cell, the rate of oxygen uptake must match the rate of diffusion across the membrane. In other words, if the cell were very large or thick, diffusion would not be able to provide oxygen quickly enough to the inside of the cell. Therefore, dependence on diffusion as a means of obtaining oxygen and removing carbon dioxide remains feasible only for small organisms or those with highly-flattened bodies, such as many flatworms (Platyhelminthes). Larger organisms had to evolve specialized respiratory tissues, such as gills, lungs, and respiratory passages accompanied by complex circulatory systems, to transport oxygen throughout their entire body.

Figure 23.6 The cell of the unicellular alga Ventricaria ventricosa is one of the largest known, reaching one to five centimeters in diameter. Like all single-celled organisms, V. ventricosa exchanges gases across the cell membrane.

Direct Diffusion

For small multicellular organisms, diffusion across the outer membrane is sufficient to meet their oxygen needs. Gas exchange by direct diffusion across surface membranes is efficient for organisms less than 1 mm in diameter. In simple organisms, such as cnidarians and flatworms, every cell in the body is close to the external environment. Their cells are kept moist and gases diffuse quickly via direct diffusion. Flatworms are small, literally flat worms, which ‘breathe’ through diffusion across the outer membrane (Figure 23.7). The flat shape of these organisms increases the surface area for diffusion, ensuring that each cell within the body is close to the outer membrane surface and has access to oxygen. If the flatworm had a cylindrical body, then the cells in the center would not be able to get oxygen.

Figure 23.7 In the flatworm, respiration is fairly simple. They rely on direct diffusion through the outer membrane. Their flat shape, rather than a cylindrical shape, allows for highly efficient diffusion to occur to fuel all the cells of their little bodies. (credit: Stephen Childs)

Skin and Gills

Earthworms and amphibians use their skin (integument) as a respiratory organ. A dense network of capillaries lies just below the skin and facilitates gas exchange between the external environment and the circulatory system. The respiratory surface must be kept moist in order for the gases to dissolve and diffuse across cell membranes.

Organisms that live in water need to obtain oxygen from the water. Oxygen dissolves in water but at a lower concentration than in the atmosphere. The atmosphere has roughly 21 percent oxygen. In water, the oxygen concentration is much lower than that. Fish and many other aquatic organisms have evolved gills to take up the dissolved oxygen from water (Figure 23.8). Gills are thin tissue filaments that are highly branched and folded. When water passes over the gills, the dissolved oxygen in water rapidly diffuses across the gills into the bloodstream. The circulatory system can then carry the oxygenated blood to the other parts of the body. In animals that contain coelomic fluid instead of blood, oxygen diffuses across the gill surfaces into the coelomic fluid. Gills are found in mollusks, annelids, and crustaceans.

Reading Question #1

Gills in fish are analogous structures to ____.

A. Skin in humans

B. Mouth of crocodiles

C. Lungs in humans

D. Scales on crocodiles

Figure 23.8. This common carp, like many other aquatic organisms, has gills that allow it to obtain oxygen from water. (credit: “Guitardude012″/Wikimedia Commons)

The folded surfaces of the gills provide a large surface area to ensure that the fish gets sufficient oxygen. Diffusion is a process in which material travels from regions of high concentration to low concentration until equilibrium is reached. In this case, blood with a low concentration of oxygen molecules circulates through the gills. The concentration of oxygen molecules in water is higher than the concentration of oxygen molecules in gills. As a result, oxygen molecules diffuse from water (high concentration) to blood (low concentration), as shown in Figure 23.9. Similarly, carbon dioxide molecules in the blood diffuse from the blood (high concentration) to water (low concentration).

Figure 23.9 As water flows over the gills, oxygen is transferred to blood via the veins. (credit “fish”: modification of work by Duane Raver, NOAA)

Tracheal Systems

Insect respiration is independent of its circulatory system; therefore, the blood does not play a direct role in oxygen transport. Insects have a highly specialized type of respiratory system called the tracheal system, which consists of a network of small tubes that carries oxygen to the entire body. The tracheal system is the most direct and efficient respiratory system in active animals. The tubes in the tracheal system are made of a polymeric material called chitin.

Insect bodies have openings, called spiracles, along the thorax and abdomen. These openings connect to the tubular network, allowing oxygen to pass into the body (Figure 23.10) and regulating the diffusion of CO2 and water vapor. Air enters and leaves the tracheal system through the spiracles. Some insects can ventilate the tracheal system with body movements.

Figure 23.10

Mammalian Systems

In mammals, pulmonary ventilation occurs via inhalation (breathing). During inhalation, air enters the body through the nasal cavity located just inside the nose (Figure 29.11). As air passes through the nasal cavity, the air is warmed to body temperature and humidified. The respiratory tract is coated with mucus to seal the tissues from direct contact with air. Mucus is high in water. As air crosses these surfaces of the mucous membranes, it picks up water. These processes help equilibrate the air to the body conditions, reducing any damage that cold, dry air can cause. Particulate matter that is floating in the air is removed in the nasal passages via mucus and cilia. The processes of warming, humidifying, and removing particles are important protective mechanisms that prevent damage to the trachea and lungs. Thus, inhalation serves several purposes in addition to bringing oxygen into the respiratory system.




Figure 23.11 Air enters the respiratory system through the nasal cavity and pharynx, and then passes through the trachea and into the bronchi, which bring air into the lungs. (credit: modification of work by NCI)

From the nasal cavity, air passes through the pharynx (throat) and the larynx (voice box), as it makes its way to the trachea (Figure 23.11). The main function of the trachea is to funnel the inhaled air to the lungs and the exhaled air back out of the body. The human trachea is a cylinder about 10 to 12 cm long and 2 cm in diameter that sits in front of the esophagus and extends from the larynx into the chest cavity where it divides into the two primary bronchi at the midthorax. It is made of incomplete rings of hyaline cartilage and smooth muscle (Figure 23.12). The trachea is lined with mucus-producing goblet cells and ciliated epithelia. The cilia propel foreign particles trapped in the mucus toward the pharynx. The cartilage provides strength and support to the trachea to keep the passage open. The smooth muscle can contract, decreasing the trachea’s diameter, which causes expired air to rush upwards from the lungs at a great force. The forced exhalation helps expel mucus when we cough. Smooth muscle can contract or relax, depending on stimuli from the external environment or the body’s nervous system.

Figure 23.12 The trachea and bronchi are made of incomplete rings of cartilage. (credit: modification of work by Gray’s Anatomy)

Lungs: Bronchi and Alveoli

The end of the trachea bifurcates (divides) to the right and left lungs. The lungs are not identical. The right lung is larger and contains three lobes, whereas the smaller left lung contains two lobes (Figure 23.13). The muscular diaphragm, which facilitates breathing, is inferior to (below) the lungs and marks the end of the thoracic cavity.

Figure 23.13 The trachea bifurcates into the right and left bronchi in the lungs. The right lung is made of three lobes and is larger. To accommodate the heart, the left lung is smaller and has only two lobes.

In the lungs, air is diverted into smaller and smaller passages, or bronchi. Air enters the lungs through the two primary (main) bronchi (singular: bronchus). Each bronchus divides into secondary bronchi, then into tertiary bronchi, which in turn divide, creating smaller and smaller diameter bronchioles as they split and spread through the lung. Like the trachea, the bronchi are made of cartilage and smooth muscle. At the bronchioles, the cartilage is replaced with elastic fibers. Bronchi are innervated by nerves of both the parasympathetic and sympathetic nervous systems that control muscle contraction (parasympathetic) or relaxation (sympathetic) in the bronchi and bronchioles, depending on the nervous system’s cues. In humans, bronchioles with a diameter smaller than 0.5 mm are the respiratory bronchioles. They lack cartilage and therefore rely on inhaled air to support their shape. As the passageways decrease in diameter, the relative amount of smooth muscle increases.

The terminal bronchioles subdivide into microscopic branches called respiratory bronchioles. The respiratorybronchioles subdivide into several alveolar ducts. Numerous alveoli and alveolar sacs surround the alveolar ducts. The alveolar sacs resemble bunches of grapes tethered to the end of the bronchioles (Figure 23.14). In the acinar region, the alveolar ducts are attached to the end of each bronchiole. At the end of each duct are approximately 100 alveolar sacs, each containing 20 to 30 alveoli that are 200 to 300 microns in diameter. Gas exchange occurs only in alveoli. Alveoli are made of thin-walled parenchymal cells, typically one-cell thick, that look like tiny bubbles within the sacs. Alveoli are in direct contact with capillaries (one-cell thick) of the circulatory system. Such intimate contact ensures that oxygen will diffuse from alveoli into the blood and be distributed to the cells of the body. In addition, the carbon dioxide that was produced by cells as a waste product will diffuse from the blood into alveoli to be exhaled. The anatomical arrangement of capillaries and alveoli emphasizes the structural and functional relationship of the respiratory and circulatory systems. Because there are so many alveoli (~300 million per lung) within each alveolar sac and so many sacs at the end of each alveolar duct, the lungs have a sponge-like consistency. This organization produces a very large surface area that is available for gas exchange. The surface area of alveoli in the lungs is approximately 75 m2. This large surface area, combined with the thin-walled nature of the alveolar parenchymal cells, allows gases to easily diffuse across the cells.

Figure 23.14 Terminal bronchioles are connected by respiratory bronchioles to alveolar ducts and alveolar sacs. Each alveolar sac contains 20 to 30 spherical alveoli and has the appearance of a bunch of grapes. Air flows into the atrium of the alveolar sac, then circulates into alveoli where gas exchange occurs with the capillaries. Mucous glands secrete mucous into the airways, keeping them moist and flexible. (credit: modification of work by Mariana Ruiz Villareal)

Protective Mechanisms

The air that organisms breathe contains particulate matter such as dust, dirt, viral particles, and bacteria that can damage the lungs or trigger allergic immune responses. The respiratory system contains several protective mechanisms to avoid problems or tissue damage. In the nasal cavity, hairs and mucus trap small particles, viruses, bacteria, dust, and dirt to prevent their entry.

If particulates do make it beyond the nose, or enter through the mouth, the bronchi and bronchioles of the lungs also contain several protective devices. The lungs produce mucus—a sticky substance made of mucin, a complex glycoprotein, as well as salts and water—that traps particulates. The bronchi and bronchioles contain cilia, small hair-like projections that line the walls of the bronchi and bronchioles (Figure 23.15). These cilia beat in unison and move mucus and particles out of the bronchi and bronchioles back up to the throat where it is swallowed and eliminated via the esophagus.

In humans, for example, tar and other substances in cigarette smoke destroy or paralyze the cilia, making the removal of particles more difficult. In addition, smoking causes the lungs to produce more mucus, which the damaged cilia are not able to move. This causes a persistent cough, as the lungs try to rid themselves of particulate matter, and makes smokers more susceptible to respiratory ailments.

Figure 23.15 The bronchi and bronchioles contain cilia that help move mucus and other particles out of the lungs. (credit: Louisa Howard, modification of work by Dartmouth Electron Microscope Facility)

Reading Questions #2

Of the following statements, which is true about the mammalian respiratory system?

A. The bronchioles are the site of gas exchange between the lungs and the bloodstream.

B. The bronchi branch out into bronchioles.

C. Air travels from the trachea to the pharynx and larynx.

D. The small surface area of the alveoli optimizes the efficiency of gas exchange.

Reading Question #3

Which one of the following is not a protective  mechanism of the human respiratory system?

A, Mucus in the alveoli

B. Hairs in the nasal cavity.

C. Cilia on the bronchi and bronchioles

d. Mucus in the lungs


Metabolomics is the scientific study of chemical processes involving metabolites. The metabolome represents the collection of all metabolites, which are the end products of cellular processes, in a biological cell, tissue, organ, or organism. Thus, while mRNA gene expression data and proteomic analyses do not tell the whole story of what might be happening in a cell, metabolic profiling can give an instantaneous snapshot of the physiology of that cell. One of the challenges of systems biology and functional genomics is to integrate proteomic, transcriptomic, and metabolomic information to give a more complete picture of living organisms.

History and Development

The idea that biological fluids reflect the health of an individual has existed for a long time. The term “metabolic profile” was introduced by Horning, et al. in 1971, after they demonstrated that gas chromatography- mass spectrometry (GC-MS; ) could be used to measure compounds present in human urine and tissue extracts. GC-MS is a method that combines the features of gas-liquid chromatography and mass spectrometry to identify different substances within a test sample. Concurrently, NMR spectroscopy, which was discovered in the 1940s, was also undergoing rapid advances. In 1974, Seeley et al. demonstrated the utility of using NMR to detect metabolites in unmodified biological samples. This first study on muscle tissue highlighted the value of NMR, in that it was determined that 90% of cellular ATP is complexed with magnesium. As sensitivity has improved with the evolution of higher magnetic field strengths and magic-angle spinning, NMR continues to be a leading analytical tool to investigate metabolism.


Figure –. Gas chromatography–mass spectrometry (GC-MS) is a method that combines the features of gas-liquid chromatography and mass spectrometry to identify different substances within a test sample.

In 2005, the first metabolomics web database for characterizing human metabolites, METLIN, was developed in the Siuzdak laboratory at The Scripps Research Institute. METLIN contained over 10,000 metabolites and tandem mass spectral data. On January 23, 2007, the Human Metabolome Project, led by Dr. David Wishart of the University of Alberta, Canada, completed the first draft of the human metabolome, consisting of a database of approximately 2500 metabolites, 1200 drugs and 3500 food components.

As late as mid-2010, metabolomics was still considered an “emerging field”. Further, it was noted that further progress in the field was in large part the result of addressing otherwise “irresolvable technical challenges” through technical evolution of mass spectrometry instrumentation. The word was coined in analogy with transcriptomics and proteomics. Like the transcriptome and the proteome, the metabolome is dynamic, changing from second to second. Although the metabolome can be defined readily enough, it is not currently possible to analyse the entire range of metabolites by a single analytical method.

Metabolites are the intermediates and products of metabolism. Within the context of metabolomics, a metabolite is usually defined as any molecule less than 1 kDa in size. However, there are exceptions to this, depending on the sample and detection method. Macromolecules such as lipoproteins and albumin are reliably detected in NMR-based metabolomics studies of blood plasma. In plant-based metabolomics, it is common to refer to “primary metabolites,” which are directly involved in growth, development and reproduction, and “secondary metabolites,” which are indirectly involved in growth, development and reproduction. In contrast, in human-based metabolomics it is more common to describe metabolites as being either endogenous (produced by the host organism) or exogenous. The metabolome forms a large network of metabolic reactions, where outputs from one enzymatic chemical reaction are inputs to other chemical reactions. Such systems have been described as hypercycles.

Separation methods: Gas chromatography, especially when interfaced with mass spectrometry (GC-MS), is one of the most widely used and powerful methods. It offers very high chromatographic resolution, but requires chemical derivatization for many biomolecules: only volatile chemicals can be analysed without derivatization.

Detection methods: Mass spectrometry (MS) is used to identify and to quantify metabolites after separation. Surface-based mass analysis has seen a resurgence in the past decade, with new MS technologies focused on increasing sensitivity, minimizing background, and reducing sample preparation.

Statistical methods: The data generated in metabolomics usually consist of measurements performed on subjects under various conditions. These measurements may be digitized spectra, or a list of metabolite levels. In its simplest form this generates a matrix with rows corresponding to subjects and columns corresponding to metabolite levels.

Key applications

  • Toxicity assessment/toxicology. Metabolic profiling, especially of urine or blood plasma samples, can be used to detect the physiological changes caused by toxic insult of a chemical or mixture of chemicals. This is of particular relevance to pharmaceutical companies wanting to test the toxicity of potential drug candidates.
  • Functional genomics. Metabolomics can be an excellent tool for determining the phenotype caused by a genetic manipulation, such as gene deletion or insertion. Sometimes this can be a sufficient goal in itself—for instance, to detect any phenotypic changes in a genetically-modified plant intended for human or animal consumption. More exciting is the prospect of predicting the function of unknown genes by comparison with the metabolic perturbations caused by deletion/insertion of known genes.

Key Points

  • The metabolome represents the collection of all metabolites in a biological cell, tissue, organ or organism, which are the end products of cellular processes.
  • Metabolites are the intermediates and products of metabolism.
  • The metabolome forms a large network of metabolic reactions, where outputs from one enzymatic chemical reaction are inputs to other chemical reactions.
  • NMR and Mass Spectroscopy are the most widely used techniques to identify metabolites.

Reading Question #4

Which molecule is responsible for the transport of oxygen in the blood?

A. Hemoglobin

B. Myoglobin

C. Testosterone

D. Auxin



Adapted from Clark, M.A., Douglas, M., and Choi, J. (2018). Biology 2e. OpenStax. Retrieved from https://openstax.org/books/biology-2e/pages/1-introduction

Kimball, J. W. (n.d.). Biology. LibreTexts Biology. Retrieved from https://bio.libretexts.org/Bookshelves/Introductory_and_General_Biology/Book%3A_Biology_(Kimball)/04%3A_Cell_Metabolism/4.05%3A_Cellular_Respiration

Boundless. (n.d.). Microbiology. LibreTexts Biology. Retrieved from https://bio.libretexts.org/Bookshelves/Microbiology/Microbiology_(Boundless)/07%3A_Microbial_Genetics/7.22%3A_Genomics_and_Proteomics/7.22C%3A__Metabolomics



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