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Thousands of chemical reactions take place every second in a living cell. By carefully studying each reaction—the reactants, the products, and the enzymes that carry out the necessary chemistry—biochemists have been able, over many years, to create a roadmap that connects which molecules feed the reactions and what happens to the products. These strings of sequential reactions, all carried out by enzymes, are called metabolic pathways. These pathways supply energy for the cell and generate the chemical building blocks cells need to carry out the business of being alive. Guiding this bustling exchange of chemical activity are enzymes, the biological catalysts that regulate the flow of materials and energy through this vast metabolic web.
In this section, we describe how metabolic pathways convert energy into biological order and discuss how enzymes facilitate the coupling of the processes that consume energy with those that release it.
Each dot on this map is a product of a metabolic reaction carried out by an enzyme. This metabolic map does not include all of the reactions that take place in a given cell, but it shows the main reactions in nearly all cells.
Breaking Down, Building Up
When you think about metabolism, you probably think about the process that burns calories in the food you eat. But metabolism involves more than the breakdown of carbohydrates, fats, and proteins to generate energy. It also includes reactions that use this energy to build molecules that are either stored for later use or become part of the structure of the cell.
Reactions that break down food molecules into the simple subunits that serve as the building blocks for complex molecules are called catabolic reactions. Cellular respiration—the process that, in the presence of oxygen (O₂), breaks down food molecules to produce energy for the cell—is a catabolic process. The carbon dioxide we exhale when we breathe is a waste product of catabolism. Sugars, for example, are broken down to yield carbon dioxide (CO₂) and water (H₂O), in addition to energy:
sugars + O2 → CO₂ + H₂O + energy
In contrast, reactions that consume energy to produce new molecules are called anabolic reactions. Photosynthesis, the most important anabolic process on Earth, uses energy derived from sunlight to convert carbon dioxide and water into sugars, producing oxygen as a by-product:
CO₂ + H₂O + light → sugars + O₂
This oxygen, which we inhale when we breathe, is consumed in cellular respiration. Although these equations are simple, the chemistry they’re based on is much more complex. Both cellular respiration and photosynthesis are multistep processes, and nearly all of those steps are carried out by enzymes that guide the reactions in the right direction and Allow them to occur at the temperature and concentrations present in living cells
Enzymes
Enzymes are biological catalysts: they speed up certain reactions by lowering the energy needed to get the reactions started. This energy barrier is called the activation energy for the reaction.
In industrial chemistry, activation energy often comes from an external source of heat. Raising the temperature increases the motion of molecules—the rate at which they jiggle and bump into their neighbors—and, so, increases the probability that molecules will collide with enough kinetic energy to form or break a chemical bond.
But cells can’t encourage chemical reactions by turning up the heat. Many cell components are temperature-sensitive, and they operate best at the range of temperatures typically found in living organisms. Proteins, for example, begin to unfold when heated. So, cells use enzymes to bring reactants together and to position them so that their reactive parts are close together, which encourages existing bonds to break and new ones to form. These molecular manipulations take place in the enzyme’s active site, the area on the surface of the enzyme where the chemistry happens.
How Enzymes Work
Explore the stages of an enzymatic reaction below.
Introduction1. Introduction
Enzymes are proteins that carry out chemical reactions. They have two special features. First, they are highly specific. Each enzyme acts only on select molecules called its substrates. Second, enzymes are catalysts. They greatly accelerate the rate of the reactions they carry out, and they are unchanged by the reactions they carry out. Enzymes don’t get used up by chemical reactions; they carry out the same reaction over and over as long as their substrate is available.
2. Binding
Enzymes have a recessed pocket on their surface called the active site. The shape of this pocket precisely matches the shape of the substrate. Molecules that don’t bind snugly in the active site don’t react. The shape of the binding pocket is the key to enzyme specificity.
This enzyme is chymotrypsin, which breaks down protein molecules in the stomach during digestion. Note how precisely the large side-chain of a specific amino acid fits in the depression within the binding site. That precise fit positions specific atoms of the substrate for reaction with atoms from the enzyme.
BindingReaction3. Reaction
Enzymes work by lowering the activation energy of a reaction. Biological molecules are generally very stable. They don’t spontaneously break down because the activation energy for that reaction is too high.
Enzymes lower the activation energy by positioning the substrate in just the right shape at just the right distance from a reaction partner for the reaction to occur in the active site.
4. Product Release
When the reaction is completed, the products diffuse out of the enzyme. You might wonder why the products don’t stick in the active site, since the substrate fit so well. It is because the products are now different molecules, with bonds and electrons in different locations. The active site binds the substrate with just enough energy to promote the reaction, but the product diffuses freely away. When the reaction is completed, the enzyme is exactly as it was before the reaction, ready to react again.
Product ReleaseMany enzyme-catalyzed reactions are reversible, and the direction in which they proceed—converting reactants to products or breaking down products into reactants—depends on the relative concentrations of the molecules involved. Many of the enzymes involved in the breakdown of glucose are also involved in glucose synthesis: when glucose reserves run low, during periods of fasting or intense physical exercise, these enzymes catalyze the reactions that produce glucose rather than break it down. Importantly, a few of the reactions in the reverse pathway are different—these reactions use ATP to drive endergonic reactions, and are the reason the pathway can run in reverse. Enzymes can power energy-requiring, endergonic reactions by linking them to energy-producing, exergonic reactions—such as the breakdown of ATP. This coupling produces enough energy to drive forward the anabolic reactions that build all of the large molecules cells need.
Medicinal Metabolites - This bit of detail from the top middle of the metabolic map at the beginning of this section shows the synthesis of the antibiotics streptomycin, neomycin, and puromycin in a bacterium. These secondary metabolic pathways are found only in select organisms. In the living universe, there are thousands of undiscovered pathways unique to certain organisms, which may yield products as important as antibiotics when they are discovered.
Key Metabolic Pathways
The enzyme-catalyzed reactions that make up a cell’s metabolism are connected in chains—metabolic pathways—so that the product of one reaction becomes a reactant, or substrate, for the next. Some of these pathways have branches, which means that the product of a reaction can continue along more than one pathway. For example, a sugar molecule can be broken down for energy or diverted to be incorporated in a cellulose polymer. These linear and branched pathways, linked by the molecules they have in common, form a complex web.
Some metabolic pathways are found in nearly all cells: for example, reaction sequences for the breakdown and synthesis of amino acids, nucleotides, carbohydrates, and lipids. These are called the central metabolic pathways. There are also a large number of pathways that lead to products that are unique to certain species, including pigments and fragrance molecules, toxins and venoms, antibiotics, and pheromones. These are called secondary metabolic pathways.
Many of the synthetic, anabolic pathways arise from common building blocks. For example, a partially assembled amino acid precursor can go down one of several different pathways to become one of several different amino acids. In the other direction, many of the breakdown pathways of metabolism ultimately converge on a small number of great metabolic highways, including two energy-yielding pathways we look at closely in the next chapter: glycolysis and the Krebs cycle. These two pathways are central routes in the catabolism of nearly all living cells—a testament to their evolutionary antiquity and to the biochemical unity that runs through all life on Earth.
Metabolic Regulation
For a cell’s metabolic economy to operate efficiently, the flow of energy and matter through its many connected reactions must be carefully controlled. Both the structure and the activity of enzymes make this regulation possible. Enzymes steer substrates through the right metabolic pathways by being very selective: each enzyme recognizes and interacts with a specific substrate (or substrates) to facilitate a particular reaction. For example, by binding and bringing together ADP and a phosphate group, ATP synthase produces ATP. This selectivity is dictated by each enzyme’s unique structure—the way its polypeptide chain folds to produce an active site optimally suited to recognize the substrates and promote their reaction.
In addition to being selective, enzymes are also flexible: they can adjust their activity to the cell’s changing needs. So if a cell finds itself with a momentary surplus of ATP, for example, enzymes that promote the catabolic breakdown of food molecules can be temporarily inhibited. A surplus of ATP can also activate the anabolic pathways that promote the production and storage of energy-rich glucose molecules.
Metabolic regulation allows cells to direct the flow of chemical traffic to suit their immediate needs, and keeps them from making substances they already have in excess. For some metabolic enzymes, the buildup of a product can slow down a reaction, because product clinging to an active site blocks the entry of substrates. This type of regulation is called product inhibition. Enzymes may also be inhibited by downstream products of a pathway. This type of regulation is called feedback inhibition, and is particularly common for enzymes that consume ATP to get over an energy hump. The buildup of a product produced farther down the pathway signals that the activity of the earlier part of the pathway is not immediately required, and chemical components and energy can therefore be directed elsewhere, possibly to storage for later use.
Metabolic Regulation - The activity of some enzymes is inhibited directly by the product of the reaction they promote. Other enzymes may be inhibited by products from further along in a pathway. The presence of elevated amounts of these products would indicate that enough of these molecules have been produced to meet the cell’s needs.
Hormonal Control
To this point, we’ve focused on metabolism as a system that provides goods and services to an individual cell. But metabolism also operates on a much larger scale, breaking down food to supply energy and biosynthetic building blocks to all of an organism’s cells and tissues. At this scale, the metabolic process needs additional levels of organization and control, including hormones to regulate the flow of materials to and from different organs, the balance between anabolic and catabolic pathways, even the amount of food we eat.
In humans and other complex multicellular organisms, different types of cells have different metabolic needs. Nerve cells, for example, rapidly metabolize glucose to provide the energy they need to pump out sodium ions; a steep electrochemical sodium gradient is necessary for nerve cells to function. Liver cells, on the other hand, can hoard glucose in the form of glycogen; this energy-rich molecule can be broken down and released to the body when energy is needed but food is scarce.
What dictates whether a cell will burn a molecule like glucose for energy or store it for later use? In addition to the substances that regulate the activity of individual enzymes, a cell’s metabolic decisions are influenced by signals that come from other cells in the body. These signals are carried by hormones, chemicals carried by the bloodstream in animals (or the sap in plants) that affect the activity of cells that recognize them.
One hormone that’s critical for the metabolism of carbohydrates and fats is insulin. Insulin promotes the absorption of glucose from the blood by liver cells and muscle cells. Individuals who lack insulin—or whose cells no longer respond to the hormone—develop diabetes. People affected by this disease have trouble controlling their blood sugar, which can damage the body’s organs and even lead to a heart attack or stroke.
Another hormone that is key in balancing food intake and energy use is leptin (from the Greek leptos, which means “thin”). This hormone, which is secreted by fat cells, controls appetite and body weight. In the 1990s, scientists studying obese mice found that a defective gene kept these animals from producing leptin. When the mice were injected with the hormone, they lost weight. Although leptin deficiency is likely the root cause of just a small percentage of obesity cases in humans, the hormone may be one of the main reasons why most diets ultimately fail. When we lose weight, our leptin levels fall, signaling the brain that we need more nutrients—a message that translates into a powerful urge to eat.
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