We have discussed some of the molecules of living organisms (carbohydrates, lipids, proteins, etc.) in the context of the functions they perform in cells and tissues. We have also looked at the structure of cells, and the types of organelles found in typical cells. We know that some of our molecules are used to provide fuel, or energy for living organisms. We know too, that this form of energy cells use is chemical energy, the energy of the electrons of atoms.

Before discussing the metabolic reactions that occur in cells, we need to discuss a few things about energy flow in cells and how cells control their metabolic reactions. The purpose of this chapter is to look at the physical laws which govern energy flow, how energy flow relates to chemical reactions and how living organisms can control the chemical reactions that occur in their cells and tissues. Much of this is the stuff of chemistry and physics, but it applies to how our cells stay alive, so we are interested, too.

Some definitions first:

Energy
Energy is often defined as the capacity to do work. The two fundamental types of energy are kinetic (energy at work, or the movement of energy) and potential (stored energy waiting to do work, such as the energy in the bonds of chemicals).

Both kinetic and potential energy can be found in many forms: electrical, light, chemical, heat, and mechanical. Under the right conditions, energy can be transformed from one type to another and from one form to another. This is a good thing, since different kinds of work require different kinds of energy, and as it applies to us, is often thought of as energy flow. Without this, we would have no life on earth. To make sense of this we have to understand both the quantity of energy available and the usefulness of that energy to do work.

Like everything else, energy transformations follow rules -- or laws, in this case the Laws of Thermodynamics (Thermodynamics is the field that studies energy transformations). There are two laws: one that addresses the quantity of available energy and the second which addresses the usefulness or availability of energy to do work.

The Two Laws of Thermodynamics

The First Law of Thermodynamics states the amount of energy in any process is constant, meaning that energy can neither be created nor destroyed by ordinary processes. (But energy can be converted from one form to another and between potential and kinetic). The first law of thermodynamics is sometimes called the "law of conservation of energy".

When we apply this law to living organisms (or any system) we say that the total amount of energy of a system and its surroundings remains constant, because energy transformations occur constantly. With each transformation within any system (such as the cells of your body) some energy escapes to the surroundings as heat energy.

The Second Law of Thermodynamics says something like "the amount of useful energy decreases when energy transformations occur", which means there is a tendency for all systems to reach the lowest possible energy. This is the famous entropy law. Entropy is the measure of the amount of disorder (loss of higher level energy) in a system. Useful is the critical term here. The amount of energy doesn't change, but the ability of that energy to do the work we need accomplished diminishes.

To give an example, Apple trees trap light waves of solar radiation in the process of photosynthesis. They use the photosynthetic products to provide energy to maintain their cells and tissues and to produce apple fruits. Apple trees are maintaining their organized structure (and function) by obtaining "fresh" energy through photosynthesis.

Plants, in this case the apples, then lose their energy to the organisms which feed on them - or - speaking plainly: An apple becomes seriously disordered as it passes through your digestive system as you process it for nutrients to maintain the organization of your cells.

This is a critical part of the second law of thermodynamics - order. Regions of concentrated energy, such as that found in the intact apple, tend to be more orderly than regions of more random energy, found in the individual molecules of the degraded apple in your intestine.

Laws of Thermodynamics, energy flow and chemical reactions
At first, when we think of the Laws of Thermodynamics, we might think that life canصt exist if we must always put energy into a system to sustain it and if all of the chemical reactions that occur in cells are increasing the amount of less useful energy.

But life on earth relies on the sun. The sun constantly loses energy (the energy of sunlight) which is trapped by green plants on earth in the process of photosynthesis. Living organisms use the products of this to sustain their cells and tissues. We survive at the expense of the sunصs increasing entropy. So we can see that while it might seem that we must violate some law of thermodynamics to have life on earth, we really donصt.

Now that we've gotten the laws down, let's turn to energy flow and chemical reactions:

A chemical reaction takes one set of substances, called the reactants, (or sometimes, the substrate) and converts them to a different set of substances, called the products.

Some chemical reactions release energy -- the amount of energy in the products is less than that of the reactants. Such reactions are said to be exergonic.

One important exergonic reaction is the breaking of the bonds of the nucleotide, ATP (our "energy" molecule). ATP has three high-energy phosphate bonds. When ATP undergoes hydrolysis, the third phosphate bond is broken, releasing energy, which can then be used to do cell work. The chemical reactions of cellular respiration (from which we produce the ATP needed) are exergonic, as we shall see in a few days.

Some chemical reactions require or consume energy -- the amount of energy in the products is more than that of the reactants. Such reactions are said to be endergonic. The dehydration synthesis that forms the peptide bond between amino acids is an example of an endergonic chemical reaction.

Given enough time, an exergonic reaction can (and will) occur spontaneously. Endergonic reactions require energy from some other source in order to take place. In living organisms the source of this needed energy is usually ATP.

In addition, most chemical reactions are reversible; the direction they take depends on the concentration of the reactants versus the concentration of the products. Chemical equilibrium exists for many cell reactions, such as the binding of oxygen to hemoglobin for transport to cells and tissues, and release of the oxygen in cells.

How does energy flow apply to living organisms?
Keeping cells alive takes work and requires energy. This energy comes from exergonic reactions within the cells that provide the free energy to perform the endergonic reactions needed to keep cells and tissues functioning. We refer to these paired reactions as coupled reactions. ATP
For some reason, in order for energy to be useful to do cell work, it must be in the form of ATP. Cells do not directly use other forms of energy, so that the energy of chemical fuel molecules must be transformed into ATP before cell work can be done. ATP is then used to provide the energy to complete an endergonic chemical reaction.

The second and third phosphate bonds of ATP are unstable. When this phosphate bond is broken by hydrolysis, energy is released (an exergonic reaction). This released energy is just perfect for the amount of energy needed for many cell reactions. This is why we call ATP an energy carrier. It "carries" the energy needed to do the cell work.

The product of the hydrolysis of ATP is a molecule of ADP and a free phosphate molecule (Pi ). The endergonic process called cell respiration makes more ATP using energy obtained by "burning" or oxidizing fuel molecules, like glucose, to bond a "new" Phosphate (Pi ) to ADP. This is a constant process in cells. About 88 pounds of ATP is made and broken in 24 hours just for basic cell maintenance. And a cell has only about a one-minute supply of ATP at any given time. The unstable ATP cannot be "stockpiled". Keep in mind, however, that not all of that 88 pounds is useful energy. Much of the energy released when ATP is broken is in the form of less useful heat energy.

When you are transferring phosphates (Pi ) from one thing to another it's called phosphorylation, a good term to know.

There are a number of additional energy carrier molecules, which we will learn when we look more closely at cell metabolic processes such as photosynthesis and cell respiration. A few of the more important ones are NAD⁺, NADP⁺, FAD and the Cytochromes.

Controlling Chemical Reactions in our Cells and Tissues
The laws of Thermodynamics that indicate the "natural" direction of any specific chemical reaction is not enough for our cells to function. Many of our metabolic reactions take place along pathways in a series of chemical reactions that must be tightly regulated for our cells to function. Fortunately, our cells have a number of means to regulate metabolism. We have mentioned two ways - coupled reactions and energy-carrier molecules. A third way cells regulate chemical reactions is by using enzymes, protein catalysts.

To summarize:

1. Cells regulate chemical reactions using enzymes, protein catalysts
2. Cells, as stated, couple enedergonic chemical reactions with exergonic chemical reactions
3. Cells, as just discussed, have energy-carrier molecules that capture energy released in exergonic reactions and transport it to endergonic reactions.

Chemical Reactions, Enzymes and Enzyme Function
Activation Energy
For any chemical reaction to get started, the reactants must come together at the right bonding place at the right time. No matter how "spontaneous" a chemical reaction is, some energy is needed to get the reaction started. This energy is called the activation energy. The activation energy is anything that increases the rate at which the reactants collide (or come together).

Remember that all atoms and molecules are in motion, so at some time, it is possible that the reactants will come together randomly. Unfortunately, the rate of a chemical reaction at normal earth temperatures may be so slow that it is imperceptible.

Hence we use catalysts, substances which can speed the rate of chemical reactions, by lowering the activation energy. It is important to know that the catalyst is not part of the chemical reaction. It is neither a reactant nor a product. A catalyst facilitates the reaction. In living organisms, we use a special class of catalysts, called enzymes.

Note: Activation energy is separate from the energy input needed to sustain endergonic reactions. Any endergonic reaction needs energy added to it to keep it going, along with getting it started.

Characteristics of Catalysts

A catalyst is not consumed in a chemical reaction

How do Enzymes Function as Catalysts?
Enzymes are almost always globular proteins with a place on the surface where the enzyme can bind to the reactant(s). This "notch" is the active site, comprised of just a few amino acids. The remainder of the enzyme helps to maintain the integrity of the active site. The active site has a precise size, shape, and electrical charge that exactly complements the reactant(s) or substrate(s). Enzymes are highly specific. Each chemical reaction that occurs in cells has its own enzyme. Enzyme shape determines its function.

When a substrate binds to the enzyme, it "fits" into the active site, temporarily distorting the reacting molecules, which is called the induced fit. This distorted stage of the substrate is called the transition state and its bonds are more easily broken (lowered activation energy), promoting the reaction. Once the reaction occurs, the active site is altered, releasing the product. The enzyme is unaffected by the reaction.

In some cases, a substance can fit into the active site but does not have the chemical bonds that the enzyme acts on, so the substance just sits on the enzyme, blocking any further enzyme activity. Such substances are enzyme inhibitors. Some poisons work in such a manor.

Enzymes and Their Environment - Enzyme Regulation
Enzyme activity is controlled by conditions of its environment. Each enzyme works at precise pH, temperature and chemical conditions, such as the amount of sodium ions in the cell. Some enzymes can only work when they have associate molecules, called coenzymes or cofactors present. Many of our vitamins function as coenzymes, and some of our minerals, notably zinc, copper and iron, function as cofactors. Other metals may interfere with enzyme function. Mercury, for example, inhibits the function of many enzymes, partly by blocking the attachment of the needed cofactor.

Enzyme regulation is a natural part of how cells function. Homeostasis in cells and organisms involves elaborate feedback mechanisms. They are essential for control of metabolism and the orderly operation of cells. Many of these metabolic controls work by activating or de-activating enzymes at appropriate times. This is the subject of enzyme regulation.

Enzyme Regulation

• The amount of enzyme present can serve to regulate the rate of some chemical reactions. And the cell's DNA controls whether an enzyme is present.
  
• Some enzymes are manufactured in an inactive form, and converted to an active form only in the presence of the proper reactant (substrate).
  
• Many chemical reactions involve a series of reactions, or steps, each of which is mediated by its own enzyme. All enzymes must be present for the reaction to reach completion. Organizing sequential enzymes on membranes or in enzyme complexes enhances their activity. Some organelles of cells do just this.
  

Enzyme Inhibition
Many enzymes are regulated by feedback mechanisms that tell the enzyme that its job is finished. Often the product of the reaction serves as this control. When enough product is formed, some of it blocks the enzyme's activity, stopping the reaction. As the product is used up, its block of the enzyme is removed, and the enzyme can be active again. This process is called feedback inhibition.

Allosteric Regulation
Some enzymes have molecules that bind to the enzyme at a specific receptor site changing its shape. Such molecules can either inhibit the enzyme when they attach or activate the enzyme when they attach. Such molecules are said to be allosteric regulators and the receptor site is an allosteric site.

Competitive Inhibition
Some enzyme inhibitors compete with the substrate for the enzyme's active site and wind up blocking the active site since they do not undergo a chemical reaction and get released from the enzyme. Substances that compete for the enzyme's active site are called competitive inhibitors. Your textbook gives the example of the competition of methanol and ethanol for the active site on the enzyme alcohol dehydrogenase.

You might note that substances that bind to the enzyme at some other place changing its shape so it can no longer function effectively are called non-competitive inhibitors. A number of poisons block enzyme activity in this way. Many pesticides block essential nervous system enzymes. Mercury inhibits the function of many enzymes, partly by blocking the attachment of the needed cofactor.

Some Vocabulary Review

Endergonic

• An energy consuming chemical reaction
  

Exergonic

• An energy releasing chemical reaction
  

Reactants

• The substance undergoing a chemical reaction.
  
• Also called: Substrate or Precursor
  

ATP

• Adenosine triphosphate, the energy currency of cells
  

Metabolism

• The chemical reactions which occur in living organisms
  

Metabolite

• Compound involved in a metabolic pathway
  

Secondary Metabolite

• Produced as a by-product or indirect product of a metabolic pathway
  

Intermediate Metabolite

• Compound in the middle of a pathway, or a compound that can branch into alternative metabolic pathways
  

Enzyme

• Protein that serves as a catalyst for a metabolic reaction
  

Cofactors

• Inorganic metal ions that work with enzymes
  

Coenzymes

• Small organic molecules (often vitamins)that work with enzymes
  

Products

• The substance(s) left or produced at the end of a metabolic reaction
  
• A by-product is a product not needed for cell use at the end
  

Oxidation

• The loss of electrons (or in cell processes, a Hydrogen ion with its electron)
  

Reduction

• The gain of electrons (or in cell processes, a Hydrogen ion with its electron)