Enzymes: Organic Catalysts
There are 4 major categories of macromolecules: carbohydrates, lipids, proteins, and nucleic acids. Most enzymes belong to the class of proteins. However, there are a few catalytic RNA molecules. Enzymes allow many chemical reactions to occur within the homeostasis constraints of a living system. Enzymes function as organic catalysts.
•Catalysts are chemicals that:
–Increase the rate of a reaction
–Are not changed by the reaction (so they can be used again)
–Do not change the nature of the reaction--the reaction could have occurred without the enzyme, just much slower
Enzymes are used all over your body! They are especially important for body processes. They make it easier for chemical reactions in the body to occur. Shown below is a table of major digestive enzymes, illustrating where they are made and released in the body.
Without enzymes, very little work could occur in our cells, meaning very little energy production;therefore, our metabolic processes would come to a screeching halt!
Why are Enzymes important?...Click on the animation tutorial below:
The first enzymes discovered were given arbitrary names. An international committee later decided to end all enzymes with the suffix –ase. Take the name of the substrate the enzyme works on and add the suffix -ase. For Example: Lactose (milk sugar) --> Lactase (enzyme)
In order to digest lactose, we need an enzyme called lactase, which is specifically designed to breakdown milk sugar in the digestive system.For some people, the amount of lactase produced in the body is not enough (Lactose intolerant) to digest lactose properly and this can cause the milk sugar to stay undigested in the gut. Any undigested lactose will then pass into the large intestine (colon) where it will be fermented by bacteria which live in the gut. These bacteria then produce gases and fatty acids which cause bloating, flatulence, stomach cramps and diarrhea.
Since names are given to enzymes based on function, an enzyme that does the same job in two different organs usually has the same name. However, the molecules may be slightly different (in areas outside the active site) and are called isoenzymes (or isozymes). For example, lactate dehydrogenase (LDH) has different subunits of isoenzymes. The different isoenzymes are tissue specific, including one found in the heart muscle and a second found in skeletal muscle and the liver.
Isoenzymes play an important role in the diagnosis of certain medical conditions. For example, hours after a heart attack, damaged heart muscle cells release enzymes into the blood. One way to determine whether an individual's chest pain was indeed due to a heart attack is to look for elevated levels of heart isoenzymes in the blood.
A few diagnostically important enzymes and the diseases of which they implicate are listed below in the table.
Enzyme names are also given by making the first part of the name apply to the function of the enzyme. For example, Phosphatases remove phosphate groups and Kinases add phosphate groups. Enzymes that participate in oxidation-reduction reactions by moving hydrogen between molecules are called Dehydrogenase enzymes.
Enzymes and Activation Energy
Many enzymes function by lowering the activation energy of reactions. By bringing the reactants closer together, chemical bonds may be weakened and reactions will proceed faster than without the catalyst.
Enzyme Form and Function
The functioning of the enzyme is determined by the shape of the protein. Most enzymes have a characteristic 3D shape or conformation.The arrangement of molecules on the enzyme produces an area known as the active site (pockets) within which the specific substrate(s) will "fit". Enzymes have a very high specificity for both the reaction it catalyzes and the substrate(s) it uses. It recognizes, confines and orients the substrate in a particular direction. The active site is the part of the enzyme where the chemical reaction actually occurs.
Lock & key Model:Lock & key Model: The shape of an enzyme allows it to do a specific job much like a lock and key. The reactants or substrates, fit into the active site like a key to a lock.
New bonds are formed between substrates as they are brought close together by the enzyme. Bonding of enzyme to substrates forms a temporary enzyme-substrate complex. This breaks to yield the products of the reaction.
Cofactors and Coenzymes
Since enzymes have a major job that is vital to life, they get help from other molecules called cofactors and coenzymes. Cofactors are helper molecules or ions that necessary for the normal activity of enzymes. Cofactor binding changes conformation of active site and aids in temporary bonding between enzyme & substrates.
An inorganic group of cofactors may include metal ions (minerals in our diets) such as Ca, Mg, Mn, Cu, Zn, & selenium. Organic cofactors for enzymes are called coenzymes. Coenzymes act as receptors and carriers for atoms or functional groups that are removed from substrates during the reaction. Many vitamins are precursors of coenzymes, such as B vitamins, vitamin C, folic acid, and biotin. Coenzymes that play important roles as H+ carriers are NAD & FAD.
Reaction Rate and Enzyme Activity
Enzyme activity is measured by the rate at which substrate is converted to product and influenced by factors listed below:
–Concentration of cofactors and coenzymes
–Concentration of enzyme and substrate
–Possible stimulatory or inhibitory effects of products on enzyme function
An increase in temperature will increase the rate of reactions until the temperature reaches a few degrees above body temperature. At this point, the enzyme is denatured.
Enzymes exhibit peak activity within a narrow pH range = pH optimum. This is due to possible changes in enzyme conformation. Optimum pH reflects the pH of the fluid the enzyme is found in. Optimum pH range for most human enzymes is from 6-8.
As the substrate concentration increases, so will the rate of the reaction until the enzyme becomes saturated = every enzyme in the solution is busy.
An analogy to saturation appeared in the early days of television on the I Love Lucy Show. Lucille Ball was working at the conveyor belt of a candy factory, loading chocolates into the little paper wraps. At first, the belt moved at a slow pace, and she and Ethel had no difficulty picking up the candy and wrapping it. The supervisor noticed what a great job they were doing and increased the speed of the belt. Lucy and her comrade had to increase their packing speed to keep up. Finally, the belt brought candy to them so fast that they could not wrap it all in because they were working at their maximum rate. That was their saturation point! (Lucy's solution was to stuff candy into her mouth and her hat to avoid getting fired). Click on the video below to view the hilarious clip!
Enzymes will continue to aid in the conversion of its substrate to product as long as there is enough substrate available and environmental conditions discussed above are ideal. However, uncontrolled enzymes would result in a disruption of homeostasis and therefore, low substrate concentrations and product would exceed demand. Thus, cell regulation takes place when enzymes are temporarily "deactivated" or turned off to prevent overproduction.
Control of enzymes occurs through inhibitors (also known as antagonists) which are chemical modulators that bind to an enzyme and turn it off, thus preventing it from further catalyzing the reaction. The inhibitors are like the guy who slips into the front of the blockbuster movie ticket line to chat with his girlfriend, the cashier. He has no interest in buying a ticket, but prevents the people in line behind him from getting their tickets for the movie !
The release of the inhibitor from the enzyme later on allows the enzyme to function and continue catalyzing the reaction. This switching occurs in different ways, depending upon whether the inhibitor is (a) competitive or (b) noncompetitive.
Enzymes and Metabolic Pathways
Most reactions are linked together in a chain (or web) called a metabolic pathway. These begin with an initial substrate and end with a final product, with many enzymatic steps along the way. Along the pathway, the product of 1 enzyme becomes the substrate of the next enzyme.
Metabolic pathways can be regulated by negative feedback (a form of cell regulation or homeostasis) that involves a product that serves as an allosteric inhibitor binding to an enzyme's allosteric site early in the pathway. In the process called allosteric inhibition, the product binds to the enzyme at a location away from the active site and changes the 3D conformation of the enzyme. This process keeps the final product from accumulating.
Click on the following link below to review animations for metabolic (biochemical) pathways and allosteric (feedback) inhibition:
Inborn Errors of Metabolism are due to inherited defects in genes for enzymes in metabolic pathways. Since each different polypeptide in the body is coded by a different gene, each enzyme protein that participates in a metabolic pathway is coded by a different gene. Therefore, inborn errors occur when there is a mutation in a single gene that codes for an enzyme in a metabolic pathway. Metabolic disease can result from either increases in intermediates formed prior to the defective enzyme or decreases in products normally formed after the defective enzyme. Examples of inborn errors of amino acid metabolism include Phenylketonuria and Albinism.
The branched metabolic pathway that begins with phenylalanine as the initial substrate is subject to numerous inborn errors of metabolism (shown in the figure below). When the enzyme (ENZ1) that converts this amino acid to the amino acid tyrosine is defective, the final product of the divergent pathway accumulates and can be detected in the blood and urine. This disease- phenylketonuria (PKU) can result in severe mental retardation and a shortened life span. If the disease is detected early during the newborn stage, brain damage can be prevented by placing the child on a diet low in the amino acid phenylalanine. If there was a defect with the enzyme (ENZ 6) that catalyzes the formation of melanin from DOPA, the condition of albinism would occur.
Let's Review Enzymes with a game of basketball:
Apply What you Have Learned...