How do proteins catalyze metabolic reactions in cells




















Metabolic diseases are most commonly the result of malfunctioning proteins or enzymes that are critical to one or more metabolic pathways.

Protein or enzyme malfunction can be the consequence of a genetic alteration or mutation. However, normally functioning proteins and enzymes can also have deleterious effects if their availability is not appropriately matched with metabolic need.

For example, excessive production of the hormone cortisol gives rise to Cushing syndrome. Clinically, Cushing syndrome is characterized by rapid weight gain, especially in the trunk and face region, depression, and anxiety. It is worth mentioning that tumors of the pituitary that produce adrenocorticotropic hormone ACTH , which subsequently stimulates the adrenal cortex to release excessive cortisol, produce similar effects. This indirect mechanism of cortisol overproduction is referred to as Cushing disease.

Patients with Cushing syndrome can exhibit high blood glucose levels and are at an increased risk of becoming obese. They also show slow growth, accumulation of fat between the shoulders, weak muscles, bone pain because cortisol causes proteins to be broken down to make glucose via gluconeogenesis , and fatigue. Other symptoms include excessive sweating hyperhidrosis , capillary dilation, and thinning of the skin, which can lead to easy bruising. The treatments for Cushing syndrome are all focused on reducing excessive cortisol levels.

Depending on the cause of the excess, treatment may be as simple as discontinuing the use of cortisol ointments. In cases of tumors, surgery is often used to remove the offending tumor.

Where surgery is inappropriate, radiation therapy can be used to reduce the size of a tumor or ablate portions of the adrenal cortex. Finally, medications are available that can help to regulate the amounts of cortisol. Insufficient cortisol production is equally problematic. It can result from malfunction of the adrenal glands—they do not produce enough cortisol—or it can be a consequence of decreased ACTH availability from the pituitary.

Victims also may suffer from loss of appetite, chronic diarrhea, vomiting, mouth lesions, and patchy skin color. Diagnosis typically involves blood tests and imaging tests of the adrenal and pituitary glands. Treatment involves cortisol replacement therapy, which usually must be continued for life.

The chemical reactions underlying metabolism involve the transfer of electrons from one compound to another by processes catalyzed by enzymes. The electrons in these reactions commonly come from hydrogen atoms, which consist of an electron and a proton. The loss of an electron, or oxidation , releases a small amount of energy; both the electron and the energy are then passed to another molecule in the process of reduction , or the gaining of an electron. These two reactions always happen together in an oxidation-reduction reaction also called a redox reaction —when an electron is passed between molecules, the donor is oxidized and the recipient is reduced.

Oxidation-reduction reactions often happen in a series, so that a molecule that is reduced is subsequently oxidized, passing on not only the electron it just received but also the energy it received. As the series of reactions progresses, energy accumulates that is used to combine P i and ADP to form ATP, the high-energy molecule that the body uses for fuel. It is important to know that the chemical reactions of metabolic pathways do not take place on their own. Each reaction step is facilitated, or catalyzed, by a protein called an enzyme.

Enzymes are important for catalyzing all types of biological reactions —those that require energy as well as those that release energy. Thermodynamics refers to the study of energy and energy transfer involving physical matter. The matter relevant to a particular case of energy transfer is called a system, and everything outside of that matter is called the surroundings. For instance, when heating a pot of water on the stove, the system includes the stove, the pot, and the water.

Energy is transferred within the system between the stove, pot, and water. There are two types of systems: open and closed. In an open system, energy can be exchanged with its surroundings. The stovetop system is open because heat can be lost to the air. A closed system cannot exchange energy with its surroundings.

Biological organisms are open systems. Energy is exchanged between them and their surroundings as they use energy from the sun to perform photosynthesis or consume energy-storing molecules and release energy to the environment by doing work and releasing heat.

Like all things in the physical world, energy is subject to physical laws. The laws of thermodynamics govern the transfer of energy in and among all systems in the universe. In general, energy is defined as the ability to do work, or to create some kind of change.

Energy exists in different forms. For example, electrical energy, light energy, and heat energy are all different types of energy.

To appreciate the way energy flows into and out of biological systems, it is important to understand two of the physical laws that govern energy. The first law of thermodynamics states that the total amount of energy in the universe is constant and conserved. In other words, there has always been, and always will be, exactly the same amount of energy in the universe. Energy exists in many different forms.

According to the first law of thermodynamics, energy may be transferred from place to place or transformed into different forms, but it cannot be created or destroyed.

The transfers and transformations of energy take place around us all the time. Light bulbs transform electrical energy into light and heat energy.

Gas stoves transform chemical energy from natural gas into heat energy. Plants perform one of the most biologically useful energy transformations on earth: that of converting the energy of sunlight to chemical energy stored within organic molecules Figure 4.

Some examples of energy transformations are shown in Figure 4. The challenge for all living organisms is to obtain energy from their surroundings in forms that they can transfer or transform into usable energy to do work. Living cells have evolved to meet this challenge. Chemical energy stored within organic molecules such as sugars and fats is transferred and transformed through a series of cellular chemical reactions into energy within molecules of ATP.

Energy in ATP molecules is easily accessible to do work. Examples of the types of work that cells need to do include building complex molecules, transporting materials, powering the motion of cilia or flagella, and contracting muscle fibers to create movement. However, the second law of thermodynamics explains why these tasks are harder than they appear.

All energy transfers and transformations are never completely efficient. In every energy transfer, some amount of energy is lost in a form that is unusable. In most cases, this form is heat energy. Thermodynamically, heat energy is defined as the energy transferred from one system to another that is not work. For example, when a light bulb is turned on, some of the energy being converted from electrical energy into light energy is lost as heat energy.

Likewise, some energy is lost as heat energy during cellular metabolic reactions. An important concept in physical systems is that of order and disorder. The more energy that is lost by a system to its surroundings, the less ordered and more random the system is. Scientists refer to the measure of randomness or disorder within a system as entropy.

High entropy means high disorder and low energy. Molecules and chemical reactions have varying entropy as well. For example, entropy increases as molecules at a high concentration in one place diffuse and spread out. The second law of thermodynamics says that energy will always be lost as heat in energy transfers or transformations. Living things are highly ordered, requiring constant energy input to be maintained in a state of low entropy.

When an object is in motion, there is energy associated with that object. Think of a wrecking ball. Even a slow-moving wrecking ball can do a great deal of damage to other objects. Energy associated with objects in motion is called kinetic energy Figure 4. A speeding bullet, a walking person, and the rapid movement of molecules in the air which produces heat all have kinetic energy. Now what if that same motionless wrecking ball is lifted two stories above ground with a crane?

If the suspended wrecking ball is unmoving, is there energy associated with it? The answer is yes. The energy that was required to lift the wrecking ball did not disappear, but is now stored in the wrecking ball by virtue of its position and the force of gravity acting on it. This type of energy is called potential energy Figure 4. If the ball were to fall, the potential energy would be transformed into kinetic energy until all of the potential energy was exhausted when the ball rested on the ground.

Wrecking balls also swing like a pendulum; through the swing, there is a constant change of potential energy highest at the top of the swing to kinetic energy highest at the bottom of the swing. Other examples of potential energy include the energy of water held behind a dam or a person about to skydive out of an airplane. Potential energy is not only associated with the location of matter, but also with the structure of matter.

For example, enzymes called kinases add phosphate groups to proteins, but enzymes called phosphatases are required to remove these phosphate groups Figure 1. Cells rely on thousands of different enzymes to catalyze metabolic reactions.

Enzymes are proteins, and they make a biochemical reaction more likely to proceed by lowering the activation energy of the reaction, thereby making these reactions proceed thousands or even millions of times faster than they would without a catalyst. Enzymes are highly specific to their substrates. They bind these substrates at complementary areas on their surfaces, providing a snug fit that many scientists compare to a lock and key.

Enzymes work by binding one or more substrates, bringing them together so that a reaction can take place, and releasing them once the reaction is complete. In particular, when substrate binding occurs, enzymes undergo a conformational shift that orients or strains the substrates so that they are more reactive Figure 3.

The name of an enzyme usually refers to the type of biochemical reaction it catalyzes. For example, proteases break down proteins, and dehydrogenases oxidize a substrate by removing hydrogen atoms. As a general rule, the "-ase" suffix identifies a protein as an enzyme, whereas the first part of an enzyme's name refers to the reaction that it catalyzes.

Figure 3: Enzymes and activation energy Enzymes lower the activation energy necessary to transform a reactant into a product. On the left is a reaction that is not catalyzed by an enzyme red , and on the right is one that is green. In the enzyme-catalyzed reaction, the enzyme binds to the reactant and facilitates its transformation into a product. Consequently, the enzyme-catalyzed reaction pathway has a smaller energy barrier activation energy to overcome before the reaction can proceed.

The proteins in the plasma membrane typically help the cell interact with its environment. For example, plasma membrane proteins carry out functions as diverse as ferrying nutrients across the plasma membrane, receiving chemical signals from outside the cell, translating chemical signals into intracellular action, and sometimes anchoring the cell in a particular location Figure 4. Figure 4: Examples of the action of transmembrane proteins Transporters carry a molecule such as glucose from one side of the plasma membrane to the other.

Receptors can bind an extracellular molecule triangle , and this activates an intracellular process. Enzymes in the membrane can do the same thing they do in the cytoplasm of a cell: transform a molecule into another form. Anchor proteins can physically link intracellular structures with extracellular structures. Figure Detail. The overall surfaces of membrane proteins are mosaics, with patches of hydrophobic amino acids where the proteins contact lipids in the membrane bilayer and patches of hydrophilic amino acids on the surfaces that extend into the water-based cytoplasm.

Many proteins can move within the plasma membrane through a process called membrane diffusion. This concept of membrane-bound proteins that can travel within the membrane is called the fluid-mosaic model of the cell membrane. In this process, energy is either stored in energy molecules for later use, or released as heat. Anabolic pathways then build new molecules out of the products of catabolism, and these pathways typically use energy.

The new molecules built via anabolic pathways macromolecules are useful for building cell structures and maintaining the cell. Figure 5: Feedback inhibition When there is enough product at the end of a reaction pathway red macromolecule , it can inhibit its own synthesis by interacting with enzymes in the synthesis pathway red arrow.

Figure Detail Not only do cells need to balance catabolic and anabolic pathways, but they must also monitor the needs and surpluses of all their different metabolic pathways. In order to bolster a particular pathway, cells can increase the amount of a necessary rate-limiting enzyme or use activators to convert that enzyme into an active conformation. Conversely, to slow down or halt a pathway, cells can decrease the amount of an enzyme or use inhibitors to make the enzyme inactive.

Such up- and down-regulation of metabolic pathways is often a response to changes in concentrations of key metabolites in the cell. For example, a cell may take stock of its levels of intermediate metabolites and tune the glycolytic pathway and the synthesis of glucose accordingly. In some instances, the products of a metabolic pathway actually serve as inhibitors of their own synthesis, in a process known as feedback inhibition Figure 5.

For example, the first intermediate in glycolysis, glucosephosphate, inhibits the very enzyme that produces it, hexokinase. This page appears in the following eBook.

Aa Aa Aa. Cell Metabolism. What Do Enzymes Do? Figure 1: Glycolysis. Energy is used to convert glucose to a 6 carbon form. Figure 2: Activation and inactivation of of enzyme reaction. Enzymes are proteins that can change shape and therefore become active or inactive. What Are Metabolic Pathways? Figure 3: Reaction pathway. Enzymes can be involved at every step in a reaction pathway. Figure 4: Catabolic and anabolic pathways in cell metabolism.



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