8.2: Enzyme Structure and Function
- Page ID
- 160793
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\(\newcommand{\avec}{\mathbf a}\) \(\newcommand{\bvec}{\mathbf b}\) \(\newcommand{\cvec}{\mathbf c}\) \(\newcommand{\dvec}{\mathbf d}\) \(\newcommand{\dtil}{\widetilde{\mathbf d}}\) \(\newcommand{\evec}{\mathbf e}\) \(\newcommand{\fvec}{\mathbf f}\) \(\newcommand{\nvec}{\mathbf n}\) \(\newcommand{\pvec}{\mathbf p}\) \(\newcommand{\qvec}{\mathbf q}\) \(\newcommand{\svec}{\mathbf s}\) \(\newcommand{\tvec}{\mathbf t}\) \(\newcommand{\uvec}{\mathbf u}\) \(\newcommand{\vvec}{\mathbf v}\) \(\newcommand{\wvec}{\mathbf w}\) \(\newcommand{\xvec}{\mathbf x}\) \(\newcommand{\yvec}{\mathbf y}\) \(\newcommand{\zvec}{\mathbf z}\) \(\newcommand{\rvec}{\mathbf r}\) \(\newcommand{\mvec}{\mathbf m}\) \(\newcommand{\zerovec}{\mathbf 0}\) \(\newcommand{\onevec}{\mathbf 1}\) \(\newcommand{\real}{\mathbb R}\) \(\newcommand{\twovec}[2]{\left[\begin{array}{r}#1 \\ #2 \end{array}\right]}\) \(\newcommand{\ctwovec}[2]{\left[\begin{array}{c}#1 \\ #2 \end{array}\right]}\) \(\newcommand{\threevec}[3]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \end{array}\right]}\) \(\newcommand{\cthreevec}[3]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \end{array}\right]}\) \(\newcommand{\fourvec}[4]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \\ #4 \end{array}\right]}\) \(\newcommand{\cfourvec}[4]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \\ #4 \end{array}\right]}\) \(\newcommand{\fivevec}[5]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \\ #4 \\ #5 \\ \end{array}\right]}\) \(\newcommand{\cfivevec}[5]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \\ #4 \\ #5 \\ \end{array}\right]}\) \(\newcommand{\mattwo}[4]{\left[\begin{array}{rr}#1 \amp #2 \\ #3 \amp #4 \\ \end{array}\right]}\) \(\newcommand{\laspan}[1]{\text{Span}\{#1\}}\) \(\newcommand{\bcal}{\cal B}\) \(\newcommand{\ccal}{\cal C}\) \(\newcommand{\scal}{\cal S}\) \(\newcommand{\wcal}{\cal W}\) \(\newcommand{\ecal}{\cal E}\) \(\newcommand{\coords}[2]{\left\{#1\right\}_{#2}}\) \(\newcommand{\gray}[1]{\color{gray}{#1}}\) \(\newcommand{\lgray}[1]{\color{lightgray}{#1}}\) \(\newcommand{\rank}{\operatorname{rank}}\) \(\newcommand{\row}{\text{Row}}\) \(\newcommand{\col}{\text{Col}}\) \(\renewcommand{\row}{\text{Row}}\) \(\newcommand{\nul}{\text{Nul}}\) \(\newcommand{\var}{\text{Var}}\) \(\newcommand{\corr}{\text{corr}}\) \(\newcommand{\len}[1]{\left|#1\right|}\) \(\newcommand{\bbar}{\overline{\bvec}}\) \(\newcommand{\bhat}{\widehat{\bvec}}\) \(\newcommand{\bperp}{\bvec^\perp}\) \(\newcommand{\xhat}{\widehat{\xvec}}\) \(\newcommand{\vhat}{\widehat{\vvec}}\) \(\newcommand{\uhat}{\widehat{\uvec}}\) \(\newcommand{\what}{\widehat{\wvec}}\) \(\newcommand{\Sighat}{\widehat{\Sigma}}\) \(\newcommand{\lt}{<}\) \(\newcommand{\gt}{>}\) \(\newcommand{\amp}{&}\) \(\definecolor{fillinmathshade}{gray}{0.9}\)- Define and describe metabolism
- Compare and contrast autotrophs and heterotrophs
- Describe the importance of oxidation-reduction reactions in metabolism
- Describe why ATP, FAD, NAD+, and NADP+ are important in a cell
- Identify the structure and structural components of an enzyme
- Describe the differences between competitive and noncompetitive enzyme inhibitors
Enzyme Structure and Function
A substance that helps speed up a chemical reaction is a catalyst. Catalysts are not used or changed during chemical reactions and, therefore, are reusable. Whereas inorganic molecules may serve as catalysts for a wide range of chemical reactions, proteins called enzymes serve as catalysts for biochemical reactions inside cells. Enzymes thus play an important role in controlling cellular metabolism.
An enzyme functions by lowering the activation energy of a chemical reaction inside the cell. Activation energy is the energy needed to form or break chemical bonds and convert reactants to products (Figure \(\PageIndex{4}\)). Enzymes lower the activation energy by binding to the reactant molecules and holding them in such a way as to speed up the reaction.
The chemical reactants to which an enzyme binds are called substrates, and the location within the enzyme where the substrate binds is called the enzyme’s active site. The characteristics of the amino acids near the active site create a very specific chemical environment within the active site that induces suitability to binding, albeit briefly, to a specific substrate (or substrates). Due to this jigsaw puzzle-like match between an enzyme and its substrates, enzymes are known for their specificity. In fact, as an enzyme binds to its substrate(s), the enzyme structure changes slightly to find the best fit between the transition state (a structural intermediate between the substrate and product) and the active site, just as a rubber glove molds to a hand inserted into it. This active-site modification in the presence of substrate, along with the simultaneous formation of the transition state, is called induced fit (Figure \(\PageIndex{5}\)). Overall, there is a specifically matched enzyme for each substrate and, thus, for each chemical reaction; however, there is some flexibility as well. Some enzymes have the ability to act on several different structurally related substrates.
The Amoeba Sisters explain enzymes and how they interact with their substrates. Vocabulary covered includes active site, induced fit, coenzyme, and cofactor. Also the importance of ideal pH and temperatures for enzymes are discussed.
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Enzymes are subject to influences by local environmental conditions such as pH, substrate concentration, and temperature. Although increasing the environmental temperature generally increases reaction rates, enzyme catalyzed or otherwise, increasing or decreasing the temperature outside of an optimal range can affect chemical bonds within the active site, making them less well suited to bind substrates. High temperatures will eventually cause enzymes, like other biological molecules, to denature, losing their three-dimensional structure and function. Enzymes are also suited to function best within a certain pH range, and, as with temperature, extreme environmental pH values (acidic or basic) can cause enzymes to denature. Active-site amino-acid side chains have their own acidic or basic properties that are optimal for catalysis and, therefore, are sensitive to changes in pH.
Another factor that influences enzyme activity is substrate concentration: Enzyme activity is increased at higher concentrations of substrate until it reaches a saturation point at which the enzyme can bind no additional substrate. Overall, enzymes are optimized to work best under the environmental conditions in which the organisms that produce them live. For example, while microbes that inhabit hot springs have enzymes that work best at high temperatures, human pathogens have enzymes that work best at 37°C. Similarly, while enzymes produced by most organisms work best at a neutral pH, microbes growing in acidic environments make enzymes optimized to low pH conditions, allowing for their growth at those conditions.
Many enzymes do not work optimally, or even at all, unless bound to other specific nonprotein helper molecules, either temporarily through ionic or hydrogen bonds or permanently through stronger covalent bonds. Binding to these molecules promotes optimal conformation and function for their respective enzymes. Two types of helper molecules are cofactors and coenzymes. Cofactors are inorganic ions such as iron (Fe2+) and magnesium (Mg2+) that help stabilize enzyme conformation and function. One example of an enzyme that requires a metal ion as a cofactor is the enzyme that builds DNA molecules, DNA polymerase, which requires a bound zinc ion (Zn2+) to function.
Coenzymes are organic helper molecules that are required for enzyme action. Like enzymes, they are not consumed and, hence, are reusable. The most common sources of coenzymes are dietary vitamins. Some vitamins are precursors to coenzymes and others act directly as coenzymes.
Some cofactors and coenzymes, like coenzyme A (CoA), often bind to the enzyme’s active site, aiding in the chemistry of the transition of a substrate to a product (Figure \(\PageIndex{6}\)). In such cases, an enzyme lacking a necessary cofactor or coenzyme is called an apoenzyme and is inactive. Conversely, an enzyme with the necessary associated cofactor or coenzyme is called a holoenzyme and is active. NADH and ATP are also both examples of commonly used coenzymes that provide high-energy electrons or phosphate groups, respectively, which bind to enzymes, thereby activating them.
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Enzyme Inhibitors
Enzymes can be regulated in ways that either promote or reduce their activity. There are many different kinds of molecules that inhibit or promote enzyme function, and various mechanisms exist for doing so (Figure \(\PageIndex{7}\)). A competitive inhibitor is a molecule similar enough to a substrate that it can compete with the substrate for binding to the active site by simply blocking the substrate from binding. For a competitive inhibitor to be effective, the inhibitor concentration needs to be approximately equal to the substrate concentration. Sulfa drugs provide a good example of competitive competition. They are used to treat bacterial infections because they bind to the active site of an enzyme within the bacterial folic acid synthesis pathway. When present in a sufficient dose, a sulfa drug prevents folic acid synthesis, and bacteria are unable to grow because they cannot synthesize DNA, RNA, and proteins. Humans are unaffected because we obtain folic acid from our diets.
On the other hand, a noncompetitive (allosteric) inhibitor binds to the enzyme at an allosteric site, a location other than the active site, and still manages to block substrate binding to the active site by inducing a conformational change that reduces the affinity of the enzyme for its substrate (Figure \(\PageIndex{8}\)). Because only one inhibitor molecule is needed per enzyme for effective inhibition, the concentration of inhibitors needed for noncompetitive inhibition is typically much lower than the substrate concentration.
In addition to allosteric inhibitors, there are allosteric activators that bind to locations on an enzyme away from the active site, inducing a conformational change that increases the affinity of the enzyme’s active site(s) for its substrate(s).
Allosteric control is an important mechanism of regulation of metabolic pathways involved in both catabolism and anabolism. In a most efficient and elegant way, cells have evolved also to use the products of their own metabolic reactions for feedback inhibition of enzyme activity. Feedback inhibition involves the use of a pathway product to regulate its own further production. The cell responds to the abundance of specific products by slowing production during anabolic or catabolic reactions (Figure \(\PageIndex{8}\)).
Already watched the Amoeba Sisters first video on enzymes and ready to explore a little more? In this video, the Amoeba Sisters cover a few examples of enzymes in the human body before emphasizing that enzymes are found in all the domains of life - and even in viruses! The importance of cofactors and coenzymes are discussed before moving into competitive and noncompetitive inhibitors. Feedback inhibition is also briefly described.
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Key Concepts and Summary
- Enzymes are biological catalysts that increase the rate of chemical reactions inside cells by lowering the activation energy required for the reaction to proceed.
- In nature, exergonic reactions do not require energy beyond activation energy to proceed, and they release energy. They may proceed without enzymes, but at a slow rate. Conversely, endergonic reactions require energy beyond activation energy to occur. In cells, endergonic reactions are coupled to exergonic reactions, making the combination energetically favorable.
- Substrates bind to the enzyme’s active site. This process typically alters the structures of both the active site and the substrate, favoring transition-state formation; this is known as induced fit.
- Cofactors are inorganic ions that stabilize enzyme conformation and function. Coenzymes are organic molecules required for proper enzyme function and are often derived from vitamins. An enzyme lacking a cofactor or coenzyme is an apoenzyme; an enzyme with a bound cofactor or coenzyme is a holoenzyme.
- Competitive inhibitors regulate enzymes by binding to an enzyme’s active site, preventing substrate binding. Noncompetitive (allosteric) inhibitors bind to allosteric sites, inducing a conformational change in the enzyme that prevents it from functioning. Feedback inhibition occurs when the product of a metabolic pathway noncompetitively binds to an enzyme early on in the pathway, ultimately preventing the synthesis of the product.