Enzymes

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Enzymes

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Within a cell hundreds of different types of chemical reactions occur as part of metabolism. Just about all these reactions would not happen at all at room temperature or else happen very slowly. These reactions are speeded up by the presence of catalysts called enzymes: organic molecules in cells that speed up chemical reactions without getting destroyed in the reaction. Just about all types of chemical reactions in the cell require enzymes. Enzymes are typically proteins, but certain types of RNA can also serve as catalysts. These RNA molecules are called ribozymes.

Catalyst

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A catalyst is a chemical that speeds up a chemical reaction without getting destroyed by the reaction.

Enzyme: An enzyme is an organic catalyst, usually a protein.

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Example of an enzyme

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If you've ever used hydrogen peroxide on a cut you know that the hydrogen peroxide produces a white 'foam'. One way to see this foam is to take a piece or raw liver in a test tube and add some hydrogen peroxide to the liver. Almost immediately the preparation will foam up. This is a great demonstration and one of the few practical uses for liver.

What's going on with the foam? In most of the cells of your body and especially liver cells is an enzyme called catylase or peroxidase which catalyses the following reaction:

 peroxide to water and oxygen

This reaction happens very slowly at room temperature, especially in the presence of light but happens much more rapidly in the presence of the enzyme. One question you probably have is why do cells have these enzymes to break down hydrogen peroxide. In cells,  these enzymes break down hydrogen peroxide compounds produced by some of the cell's metabolic reactions especially the transfer of hydrogens from organic compounds such as formaldehyde and ethyl alcohol to oxygen. This takes place in organelles called peroxisomes. In some parasites this set of reactions serves to eliminate excess oxygen.

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How enzymes operate

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The operation of enzymes depends on the fit between the enzyme and the starting molecule or molecules in the reaction that the enzyme catalyses. This is shown in a simple fashion here.

substrate + enzyme --------> enzyme substrate complex -----------> enzyme + products.

Substrate: The starting molecules for a chemical reaction are called the substrates.

Enzyme substrate complex: The enzyme substrate complex is transitional step when the substrates of a chemical reaction are bound to the enzyme.

Active site: The area on the enzyme where the substrate or substrates attach to is called the active site. Enzymes are usually very large proteins and the active site is just a small region of the enzyme molecule.

 

induced fit modelIt used to be thought that the substrate and the active site had to have an exact fit for the enzyme to operate. This idea is what used to be called the 'lock and key' model of enzyme activity. We now know the situation is much more complex.

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Induced fit model:

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Our current general model of how enzymes operate is called the 'induced fit' model. The idea is that  the enzyme's active site does not have the exact shape of  substrate, but the substrate brings about or induces a change in the shape of the active site. A good analogy is what happens when you try to catch a softball. You don't hold your hand rigidly in the shape that best fits the ball, but alter the shape of your hand to accommodate the ball. The idea is illustrate in this animation. Here the dark green region represents the active site of an enzyme. The two purplish ovals represent substrates that are going to join together at the active site to form a product(red). Notice how the active site changes shape to conform(more or less) to the substrates.

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Enzymes and activation energy

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All chemical reactions require some amount of energy to get them started. This energy is called activation energy. The way enzymes operate is by effectively lowering the amount of activation energy required for a chemical reaction to start.  Sometimes this happens because enzymes might weaken a covalent bond within a substrate molecule. In other cases this lowering of activation energy seems to happen because the enzyme holds the substrate molecules in a particular position that increases the likely that the molecules are going to react.

Energy hill diagrams are a good way to visualize the effect of enzymes on activation energy. The diagram shows time on the horizontal axis and the amount of energy in the chemicals involved in a chemical reaction on the vertical axis. The point if this diagram again is that without the enzyme, much more activation energy is required to get a chemical reaction to take place.

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Factors affecting enzyme activity

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Physical factors

Enzymes typically operate best in a relatively narrow range of environmental conditions.

Many of the enzymes in our bodies work best at body temperature. At significantly lower temperatures the substrate molecules do not have enough kinetic energy for the reaction to take place even in the presence of the enzyme. At body temperatures significantly higher than normal, the enzyme will not work well because the kinetic energy from the molecules in the solution containing the enzyme is so high, that the enzyme's shape is pulled apart to he point that the enzyme is not able to properly function.

Indeed the enzyme's structure may be so disrupted or denatured hat the enzyme molecule cannot return to its original shape. Indeed the danger of high fevers stems in large part from the potential damage to enzymes and other proteins from the high temperature. pH, salinity and concentrations of other ions also affect enzyme shape.

The diagram shows hypothetical relationships between temperature and enzyme activity for a human and for a thermophilic(heat loving) bacteria. Notice the optimum activity level for each enzyme matches the environment that the enzyme has to work in. Human enzymes generally work best at our temperature(37C) while the thermophilic bacteria's enzyme works best at a higher temperature. Indeed some of these thermophilic organisms live quite nicely at the boiling point of water.

 

 

 

 

 

Cofactors and Coenzymes

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Many enzymes need companion molecules in order to function. For example, many enzymes such as alcohol dehydrogenase require organic molecules or various metals to function properly.  These are called cofactors. If the companion is an organic molecule then the companion is often called a coenzyme. For instance, zinc is a common cofactor for many enzymes including the alcohol dehydrogenase. Many vitamins are coenzymes. For example Vitamin B2(Riboflavin) is an important coenzyme in cellular respiration. Another vitamin, Pantothenic acid is what's called 'Coenzyme A' in cellular respiration.  Indeed the group of vitamins called the 'B complex' are all important coenzymes. NOTE: the term cofactor refers to either inorganic ions or atoms that work with enzymes or to organic molecules such vitamins that work with enzymes. The word coenzyme refers just to the organic molecules.

Inhibitors

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Various substances interfere with the operation of enzymes. These substances are called inhibitors. Organophosphates and certain other pesticides operate by inhibiting key enzymes in the nervous system.  Both carbon monoxide and oxygen bind  the same active site in the hemoglobin molecule and carbon monoxide binds so strongly to this site that oxygen can't bind properly to the hemoglobin. This type of situation where one substrate out competes another is called competitive inhibition.

Feedback Inhibition

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Sometimes the product of a chemical reaction involving an enzyme attaches to a secondary site on the enzyme and inhibits the enzyme's ability to continue the reaction. This type of reversible inhibition is called feedback inhibition and it provides cells with a way to regulate the production of various compounds in the cell. The diagram shows a simple illustration of feedback inhibition for a metabolic pathway involving three chemicals and two enzymes.

pgd created 12/01/00 revised 04/26//02

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