Metabolism Health Article

Definition

Metabolism refers to the highly integrated network of chemical reactions by which living cells grow and sustain themselves.

Description

The metabolism's network of chemical reactions are composed of two major types of pathways: anabolism and catabolism. Anabolism uses energy stored in the form of adenosine triphosphate (ATP) to build larger molecules from smaller molecules. Catabolic reactions degrade larger molecules in order to produce ATP and raw materials for anabolic reactions.

Function

Together, the body's anabolic and catabolic networks have three major functions:

• to extract energy from nutrients
• to synthesize the building blocks that make up the large molecules of life: proteins, fats, carbohydrates, nucleic acids, and combinations of these substances
• to synthesize and degrade molecules required for special functions in the cell

These reactions are controlled by enzymes, protein catalysts that increase the speed of chemical reactions in the cell without themselves being changed. Each enzyme catalyzes a specific chemical reaction by acting on a specific substrate, or raw material. Each reaction is just one in a sequence of catalytic steps in a metabolic pathway(s). These sequences may be composed of up to 20 enzymes, each one creating a product that becomes the substrate or raw material for the subsequent enzyme. Often, an additional molecule called a coenzyme, is required for the enzyme to function. For example, some coenzymes accept an electron that is released from the substrate during the enzymatic reaction. Most of the water-soluble vitamins of the B complex serve as coenzymes; riboflavin (vitamin B₂) for example, is a precursor of the coenzyme flavine adenine dinucleotide, while pantothenate is a component of coenzyme A, an important intermediate metabolite.

The series of products created by the sequential enzymatic steps of anabolism or catabolism are called metabolic intermediates, or metabolites. Each step represents a small change in the molecule, usually the removal, transfer, or addition of a specific atom, molecule or group of atoms that serves as a functional group, such as the amino groups (-NH₂) of proteins.

Typically, these metabolic pathways are linear. That is, they begin with a specific substrate and end with a specific product. Some pathways, such as the Krebs cycle, are cyclic. Often, metabolic pathways also have branches that feed into or out of them. The specific sequences of intermediates in the pathways of cell metabolism are called intermediary metabolism.

There are thousands of chemical reactions in the body and many of these pathways are identical in most forms of life.

According to the first law of thermodynamics, in any physical or chemical change, the total amount of energy in the universe remains constant, that is, energy cannot be created or destroyed. Thus, when the energy stored in nutrient molecules is released and captured in the form of ATP, some energy is lost as heat but the total amount of energy is unchanged.

The second law of thermodynamics states that physical and chemical changes proceed in such a direction that useful energy undergoes irreversible degradation into a randomized form—entropy. The dissipation of energy during metabolism represents an increase in the randomness, or disorder, of the organism's environment. Because this disorder is irreversible, it provides the driving force and direction to all metabolic enzymatic reactions.

Even in the simplest cells, such as bacteria, there are at least a thousand such reactions. Regardless of the number, all cellular reactions can be classified as one of two types of metabolism: anabolism and catabolism. These reactions, while opposite in nature, are linked through the common bond of energy. Anabolism, or biosynthesis, is the synthetic phase of metabolism during which small building block molecules, or precursors, are built into large molecular components of cells, such as carbohydrates and proteins.

Catabolic reactions are used to capture and save energy from nutrients, as well as to degrade larger molecules into smaller, molecular raw materials for reuse by the cell. The energy is stored in the form of energy-rich ATP, which powers the reactions of anabolism. The useful energy of ATP is stored in the form of a high-energy bond between the second and third phosphate groups of ATP. The cell makes ATP by adding a phosphate group to the molecule adenosine diphosphate (ADP). Therefore, ATP is the major chemical link between the energy-yielding reactions of catabolism, and the energy-requiring reactions of anabolism.

In some cases, energy is also conserved as energyrich hydrogen atoms in the coenzyme nicotinamide adenine dinucleotide phosphate (NADPH) in the reduced form of NADPH. The NADPH can then be used as a source of high-energy hydrogen atoms during certain biosynthetic reactions of anabolism.

In addition to the obvious difference in the direction of their metabolic goals, anabolism and catabolism differ in other significant ways. For example, the various degradative pathways of catabolism are convergent. That is, many hundreds of different proteins, polysaccharides and lipids are broken down into relatively few catabolic end products. The hundreds of anabolic pathways, however, are divergent. That is, the cell uses relatively few biosynthetic precursor molecules to synthesize a vast number of different proteins, polysaccharides and lipids.

The opposing pathways of anabolism and catabolism may also use different reaction intermediates or different enzymatic reactions in some of the steps. For example, there are 11 enzymatic steps in the breakdown of glucose into pyruvic acid in the liver. But the liver uses only nine of those same steps in the synthesis of glucose, replacing the other two steps with a different set of enzyme-catalyzed reactions. This occurs because the pathway to degradation of glucose releases energy, while the anabolic process of glucose synthesis requires energy. The two different reactions of anabolism are required to overcome the energy barrier that would otherwise prevent the synthesis of glucose.

Another reason for having slightly different pathways is that the corresponding anabolic and catabolic routes must be independently regulated. Otherwise, if the two phases of metabolism shared the exact pathway (only in reverse) a slowdown in the anabolic pathway would slow catabolism, and vice versa.

In addition to regulating the direction of metabolic pathways, cells, especially those in multicellular organisms, also exert control at three different levels: allosteric enzymes, hormones, and enzyme concentration.

Allosteric enzymes in metabolic pathways change their activity in response to molecules that either stimulate or inhibit their catalytic activity. While the end product of an enzyme cascade is used up, the cascade continues to synthesize that product. The result is a steady-state condition in which the product is used up as it is produced and there is no significant accumulation of product. However, when the product accumulates above the steady-state level for any reason, in excess of the cell's needs, the end product acts as an inhibitor of the first enzyme of the sequence. This process is called allosteric inhibition, and is a type of feedback inhibition.

A classic example of allosteric inhibition is the case of the enzymatic conversion of the amino acids: L-threonine into L-isoleucine by bacteria. The first of five enzymes, threonine dehydratase is inhibited by the end product, isoleucine. This inhibition is very specific, and is accomplished only by isoleucine, which binds to a site on the enzyme molecule called the regulatory, or allosteric, site. This site is different from the active site of the enzyme, which is the site of the catalytic action of the enzyme on the substrate, or molecule being acted on by the enzyme.

Some allosteric enzymes may be stimulated by modulator molecules. These molecules are not the end product of a series of reactions, but rather may be the substrate molecule itself. These enzymes have two or more substrate binding sites, which serve a dual function as both catalytic sites and regulatory sites. Such allosteric enzymes respond to excessive concentrations of substrates that must be removed. Also, some enzymes have two or more modulators with opposite effects and possess their own specific allosteric site. When occupied, one site may speed up the catalytic reaction, while the other may slow it down. ADP and AMP (adenosine monophosphate) stimulate certain metabolic pathway enzymes, for example, while ATP inhibits the same allosteric enzymes.

The activity of allosteric enzymes in one pathway may also be modulated by intermediate or final products from other pathways. Such cross-reaction is an important way in which the rates of different enzyme systems can be coordinated with each other.

Hormonal control of metabolism is regulated by chemical messengers secreted into the blood by different endocrine glands. These messengers, called hormones, travel to other tissues or organs, where they may stimulate or inhibit specific metabolic pathways.

A classic example of hormonal control of metabolism is the hormone adrenaline, which is secreted by the medulla of the adrenal gland and carried by the blood to the liver. In the liver, adrenaline stimulates the breakdown of glycogen to glucose, increasing the blood sugar level. In the skeletal muscles, adrenaline stimulates the breakdown of glycogen to lactate ATP.

Adrenaline exerts its effect by binding to a receptor site on the cell surfaces of liver and muscle cells. From there, adrenaline initiates a series of signals that ultimately causes an inactive form of the enzyme glycogen phosphorylase to become active. This enzyme is the first in a sequence that leads to the breakdown of glycogen to glucose and other products.

Finally, the concentration of the enzymes themselves exert a profound influence on the rate of metabolic activity. For example, the ability of the liver to turn enzymes on and off—a process called enzyme induction—assures that adequate amounts of needed enzymes are available, while inhibiting the cell from wasting its energy and other resources on making enzymes that are not needed.

For example, in the presence of a high-carbohydrate, low-protein diet, the liver enzymes that degrade amino acids are present in low concentrations. In the presence of a high-protein diet, however, the liver produces increased amounts of enzymes needed for degrading these molecules.

The basis of both anabolic and catabolic pathways is the reactions of reduction and oxidation. Oxidation refers to the combination of an atom or molecule with oxygen, or the loss from it of hydrogen or of one or more electrons. Reduction, the opposite of oxidation, is the gain of one or more electrons by an atom or molecule. The nature of these reactions requires them to occur together; i.e., oxidation always occurs in conjunction with reduction. The term "redox" refers to this coupling of reduction and oxidation.

Redox reactions form the basis of metabolism and are the basis of oxidative phosphorylation, the process by which electrons from organic substances such as glucose are transferred from organic compounds such as glucose to electron carriers (usually coenzymes), and then are passed through a series of different electron carriers to molecules of oxygen molecules. The transfer of electrons in oxidative phosphorylation occurs along the electron transport chain. During this process, called aerobic respiration, energy is released, some of which is used to make ATP from ADP. The major electron carriers are the coenzymes nicotinamide adenine dinucleotide (NADH) or flavin adenine dinucleotide (FADH₂). Oxidative phosphorylation is the major source of ATP in aerobic organisms, from bacteria to humans.

Some anaerobic bacteria, however, also carry out respiration, but use other inorganic molecules, such as nitrate (NO₃ ^-) or sulfate (SO₄ ^2-) ions as the final electron acceptors. In this form of respiration, called anaerobic respiration, nitrate is reduced to nitrite ion (NO₂ ^-), nitrous oxide (N₂O) or nitrogen gas (N₂), and sulfate is reduced to form hydrogen sulfide (H₂S).

Much of the metabolic activity of cells consists largely of central metabolic pathways that transform large amounts of proteins, fats and carbohydrates. Foremost among these pathways are glycolysis, which can occur in either aerobic or anaerobic conditions, and the Krebs cycle, which is coupled to the electron transport chain, which accepts electrons removed from reduced coenzymes of glycolysis and the Krebs cycle. The final electron acceptor of the chain is usually oxygen, but some bacteria use specific, oxidized ions as the final acceptor in anaerobic conditions.

As vital as these reactions are, there are other metabolic pathways in which the flow of substrates and products is much smaller, yet the products quite important. These pathways constitute secondary metabolism, which produces specialized molecules needed by the cell or by tissues or organs in small quantities. Such molecules may be coenzymes, hormones, nucleotides, toxins, or antibiotics.

The process of extracting energy by the central metabolic pathways that break down fats, polysaccharides and proteins, and conserving it as ATP, occurs in three stages in aerobic organisms. In anaerobic organisms, only one stage is present. In each case, the first step is glycolysis.