Study Guide Midterm (Chapters 6-11).pdf

PHA 339: Biochemistry for Healthcare Professionals Midterm Study Guide (Part 2) (Chapters 6-11) Fall 2024 Chapter 6: Basic Concepts of Enzyme Action Understand that enzymes are c...

PHA 339: Biochemistry for Healthcare Professionals Midterm Study Guide (Part 2) (Chapters 6-11) Fall 2024 Chapter 6: Basic Concepts of Enzyme Action Understand that enzymes are catalysts. Know how enzymes accelerate the rate of reactions by facilitating the formation of the transition state. Know that enzymes provide specificity for chemical reactions. Understand the role of cofactors as well as the term apoenzyme and holoenzyme. Understand the significance of Gibbs Free Energy and how this may be used to predict the whether chemical reactions are spontaneous. Know the difference between ΔG, ΔG0, and ΔG±. Know the meaning of ΔG = negative number, ΔG = positive number, and ΔG = zero. Know that the more accurate picture for the formation of the enzyme-substrate complex is through an induced fit model rather than the classic lock-and-key mechanism. Recognize the importance of transition state analogues and that these compounds are mimicking the interaction of the enzyme-substrate transition state. Chapter 7: Kinetics and Regulation Know the concept of first-order and second-order kinetics. First order: only one molecule influencing rate of reaction Second order: 2 molecules influencing rate of reaction, more of either molecule will increase rate of reaction Know the general scheme of an enzyme reacting with a substrate and how this leads to the enzyme-substrate complex and the conversion to products. Know the Michaelis-Menten model: how it is based on one substrate, the importance of the formation of the enzyme-substrate complex, the steady state approximation, and KM. Describe the general shape of the Michaelis-Menten curve and that it approaches as Vmax asymptotically. Know that KM is equal to the substrate concentration when the reaction velocity is half of its maximum value. Also, the smaller the value of KM, the greater the affinity of the substrate for the enzyme based on its definition with k1 in the denominator. Understand that the ratio kcat/KM is a measure of catalytic efficiency.  Know that for more complicated enzyme catalyzed reactions with two substrates, the kinetics follows a sequential model (ordered or random) or a double-displacement model (ping-pong kinetics). Sequential (induced fit) All substrates must bind to enzyme before any product is made Double displacement One product is released before second substrate is bound to enzyme One at a time Like a team passing one ball around Know that allosteric enzymes are catalysts and information sensors. Understand the concept and biological reasons for a feedback inhibition mechanism. Know how you can look at a graph and determine whether the enzyme is a Michalis- Menton enzyme (hyperbolic type curve) or an allosteric enzyme (sigmoidal curve). Michaelis-menten=hyperbolic Allosteric=sigmoidal Understand the concept of a T state and an R state, the equilibrium between the two, and the biochemical ramifications. 2 conformations of hemoglobin T=tense, deoxygenated R=relaxed, oxygenated Equilibrium between the 2 happen when partial pressure of oxygen is at a specific level Chapter 8: Mechanisms and Inhibitors Understand how environmental factors (e.g., temperature, pH, and inhibitory molecules) can affect enzyme activity. Know the terms competitive inhibitor, uncompetitive inhibitor, and noncompetitive inhibitor. Competitive=structurally similar and binds to active site so substrate can’t bind Uncompetitive=binds ONLY to ESC Noncompetitive=binds either to enzyme or ESC, does not prevent substrate from binding Understand the general concept of affinity labels. structurally similar to the enzyme’s substrate but inhibit the enzyme by covalently modifying an amino acid in the active site You need to understand the concept of covalent catalysis of chymotrypsin. Rapid state: acylation→formation of acylenzyme intermediate Slow state: slow release of acyl component Enzyme makes a temporary bond with the starting material so it can be changed into a product. After product is created, it lets go and is recycled. You need to know about the catalytic triad and its role in enzyme hydrolysis. Serine Histidine Aspartate Helps enzyme break down molecules Know the general concept of the oxyanion hole and the stabilizing effects on the oxygen anion of the tetrahedral intermediate. stabilizes the negative charge on the tetrahedral intermediate during peptide bond cleavage  Chapter 9: Hemoglobin, an Allosteric Protein Understand the oxygen binding curves for hemoglobin and myoglobin. Know that hemoglobin is a tetrameric structure whereas myoglobin is not. Describe cooperativity and its affects on oxygen binding curves. Positive cooperativity: when oxygen binds to hemoglobin, the remaining hemoglobin chains have a greater affinity for oxygen. Know the structural details of the heme group in hemoglobin and myoglobin and its function (e.g., ferrous oxidation state of ion, proximal/distal histidine residues, and binding of oxygen). A heme group is a ring-shaped molecule that contains iron and is a vital component of hemoglobin and other proteins. The iron in heme group is essential because it can bind to oxygen Hemoglobin=tetramer Myoglobin=monomer Hemoglobin also exhibits cooperative binding, meaning the binding of oxygen to one heme group influences the others, making it easier for more oxygen to bind. Myoglobin does not exhibit cooperative binding and is better suited for storing oxygen in muscle tissue. Hemoglobin=sigmoidal curve Myoglobin=hyperbolic curve Without knowing all the details, understand that binding oxygen to heme in hemoglobin results in a conformational change that increases the affinity of the cofactors for oxygen. Know the Bohr effect and its biological ramifications. a phenomenon that describes how hemoglobin's affinity for oxygen decreases when blood pH decreases or carbon dioxide levels increase How is oxygen is transported in red blood cells? oxygen is transported in red blood cells by binding to heme How is carbon dioxide is transported in red blood cells? bicarbonate Know that carbon dioxide can react with hemoglobin to form carbamates. carbon dioxide+hemoglobin=carbamate What does 2,3-BPG bind to? the central cavity of deoxyhemoglobin  Know the role of hydrogen ions play in release of oxygen and carbon dioxide. Bohr effect What happens in sickle cell anemia? There is a mutation in one amino acid.  Chapter 10: Carbohydrates Understand the meaning of ketoses and aldoses. Ketoses=monosaccharide whose carbon skeleton has ketone group Aldoses= monosaccharide whose carbon skeleton has aldehyde group 2 different types of monosaccharides Know that carbohydrates have the D stereochemistry unlike amino acids. Stereochemistry=mirror images L isomer=left hand D isomer=right hand Know the terms monosaccharides. All monosaccharides consist of a carbon chain backbone, and each carbon on that chain is bound to an oxygen, with either a single or double bond. Understand hemiacetal and hemiketal formations and how this is possible in carbohydrates through intramolecular bonding. Hemiacetal=carbon with aldehyde group at end of sugar chain hugs oxygen Hemiketal= carbon with ketone group in middle of sugar chain hugs oxygen EXAMPLE: glucose forms hemiacetal when it makes a ring because it is a sugar with an aldehyde group, fructose forms hemiketal when it makes a ring because it is a sugar with a ketone group A sugar can never have BOTH an aldehyde and ketone group. Know the term mutarotation. Imagine a sugar molecule is like a toy car with wheels that can flip in different directions. When a sugar is floating in water, it can switch between two shapes. These shapes are called alpha (α) and beta (β). The sugar molecule keeps flipping back and forth between these two shapes over time. This flipping between alpha and beta forms is called mutarotation. Be able to identify anomeric carbons and the anomeric effect. The anomeric carbon is the carbon in a sugar molecule that was originally part of the aldehyde (in aldoses) or the ketone (in ketoses) group before the sugar ring closes. When the sugar forms a ring, this carbon is the one that decides whether the sugar will be in the alpha (α) or beta (β) form. the anomeric carbon is the one connected to two oxygens after the sugar forms a ring. Anomeric effect: anomeric carbon is picky about who it likes to be next to, so it will stay close or push away group of atoms. This preference of who gets to hang out with the anomeric carbon changes how the sugar behaves (more or less stable) Know the nomenclature discussed in class of furanose and pyranose as well as alpha/beta stereochemical positions in cyclic carbohydrates (e.g., α or β fructopyranose and fructofuranose). Differ in size of cyclic rings Hemiacetal=pyranose Hemiketal=furanose Understand and be able to identify reducing sugars. Reducing sugars are special types of sugars that can help in a chemical reaction called reduction. They can give away electrons or hydrogen, making other  substances change. Look for Functional Groups: Reducing sugars have free aldehyde or ketone groups when in their open-chain form. Use Fischer projections to determine R/S configurations. R and S configurations are different ways to spatially arrange atoms around a chiral center. Be able to convert Fischer projections to Haworth structures or the reverse. Know the structure of glucose and the up-down relationship in Haworth structures with the hydroxyl groups of the open chain structure. Beta=up Alpha=down Know the meaning of oligosaccharides. Small chains of sugar units (like few building blocks linked together) Understand that carbohydrates can form O-glycosidic bonds. An O-glycosidic bond is a type of chemical bond that forms between the oxygen atom of a hydroxyl group (–OH) on one sugar and the anomeric carbon (the carbon that was involved in forming the ring structure of the sugar) of another sugar or molecule. Know the meaning of α-1,4-glycosidic bonds, β-1,4-glycosidic bonds, etc. Both types of O-glycosidic bonds α-1,4-glycosidic bonds helical shape hydroxyl group attached to anomeric carbon is pointing down β-1,4-glycosidic bonds straight the hydroxyl group attached to the anomeric carbon is pointing up Carbohydrates+proteins=glycoproteins Chapter 11: Lipids Know that lipids are highly water-insoluble molecules with correspondingly high solubility in organic solvents. Be able to identify molecular structures of free fatty acids, triacylglycerols, and phospholipids. A free fatty acid molecule consists of a long hydrocarbon chain with a carboxylic acid group (-COOH) at one end. Be able to identify polyunsaturated and polysaturated lipids. Polyunsaturated=double bond Saturated=no double bonds  Know the short-hand representation of a phospholipid as a sphere with two hydrocarbon chains. How are fatty acids stored? triacylglycerols Know that phospholipids form cell membranes. Be able to identify the 6-6-6-5 carbon structural framework linear chain of three benzene rings with a single carbon "tail" at the end steroids