Lecture 7: Metabolism and Enzymes PDF

Lecture 7 Metabolism and Enzymes Reminders: Quiz 2 (covers Lectures 5-7) Release Date: Oct 2 at 7:00 pm Due Date: Oct 3 by 7:00 pm...

Lecture 7 Metabolism and Enzymes Reminders: Quiz 2 (covers Lectures 5-7) Release Date: Oct 2 at 7:00 pm Due Date: Oct 3 by 7:00 pm Textbook reference sections/pages: Objectives: Morris text – Chapter 6 (pp. 114 – 116 and 123- Introduction to Metabolism 129) Enzymes Section 6.1 Overview of Metabolism Section 6.5 Enzymes You can read sections 6.2, 6.3 ad 6.4 as review if you wish – not required BIOL1010 and 1  Cells Need Energy! Cells must harness energy from the environment and convert it to a form that allows them to do work – Synthesizing DNA, RNA, and proteins – Moving vesicles in a cell – Pumping substances across membranes Cells use ATP for energy – ATP contains energy in its chemical bonds BIOL1010 and 2  Metabolism Overview Important to consider a cell’s sources of carbon because: – Carbon is fundamental in organic molecules in cells – Carbon-based compounds are a stable energy storage form Organisms have two ways of harvesting energy from their environment and two sources of carbon… BIOL1010 and 3  Metabolism Overview Metabolic Classification: BIOL1010 and 4  Metabolism Overview Many cellular chemical reactions are linked so that the products of one reaction are the reactants of the next reaction, forming pathways. Metabolism is the building and breaking down of carbon sources to harness or release energy. Anabolism = Catabolism = building of breakdown of molecules; input molecules; ATP of ATP required produced BIOL1010 and 5  Enzymes and the Rate of Chemical Reactions From your readings, you now know how to tell whether a reaction is spontaneous and in what direction the reaction occurs. Rate of chemical reactions is also important Chemical reactions in cells are catalyzed by proteins called enzymes. As a new compound is forming, there briefly exists a transition state – old bonds are breaking and new ones are forming during this transition state – This transition state is unstable and, therefore, has a large amount of free energy. BIOL1010 and 6  Enzymes and the Rate of Chemical Reactions Activation Energy is energy (EA) released here If activation energy is high, is the reaction faster or slower? Difference in free energy between reactants and products (ΔG) does not change BIOL1010 and 7  Enzymes and the Rate of Chemical Reactions It is important to note that spontaneous reactions can be slow – Catalysts accelerate reactions In an enzyme-catalyzed reaction: = Substrate (S) ⇌ Product (P) reactant S + Enzyme (E) ⇌ ES ⇌ EP ⇌ E + P Complex The substrate dissociates; E forms a complex Substrate is converted and P released with the enzyme into product while still part of the complex with the enzyme (EP). BIOL1010 and 8  Enzymes and the Rate of Chemical Reactions Formation of ES is critical to speeding up reactions 3-D structure of enzymes important because it aligns specific amino acids to form the active site Substrate + active site interactions are: weak noncovalent interactions or transient covalent bonds Stabilize the transition state and decrease the activation energy required for the reaction. BIOL1010 and 9  Enzymes and the Rate of Chemical Reactions Active Site Formation: – An enzyme’s active site is extremely small compared to the enzyme itself. – The active-site amino acids may be spaced far apart in the primary sequence of the enzyme, but when the protein is folded, they come together to form the active site. BIOL1010 and 10  Enzymes and the Rate of Chemical Reactions Enzyme Specificity – Enzymes are highly specific for both the substrate and the reaction that is catalyzed. Enzymes catalyze only one reaction or a very limited number of reactions – E.g. succinate dehydrogenase acts only on succinate – E.g. β-galactosidase only cleaves the glycosidic bonds linking galactose to glucose in lactose BIOL1010 and 11  Enzymes and the Rate of Chemical Reactions Enzyme Kinetics – Enzymes speed up rate of chemical reactions – Simplest model of enzyme action involves a single substrate, enzyme and product (Michaelis-Menten Kinetics) Reaction rate increases as substrate concentration increases to a point - Vmax The smaller the Km, the less substrate is needed for enzyme to become saturated and Km = Michaelis- the lower the substrate concentration needed Menten constant to achieve Vmax BIOL1010 and 12  Enzymes and the Rate of Chemical Reactions Enzyme Activity Influencers – Enzyme activity can be influenced by: Temperature pH Enzymes have optimal temperature Enzymes have optimal pH Low temperature  low activity Cytoplasmic enzymes – pH 7 Increased activity as temperature Digestive system enzymes - increases pH between 1 and 3 Denaturation at very high Enzymes in lysosomes – pH 5 temperatures pH can affect how enzyme folds Different enzymes work best at different pH can affect the charges of amino temperatures acids making up the active site E.g. Human enzymes  37 C Influences how well substrate binds to active site E.g. Thermophilic bacteria  very high temps BIOL1010 and 13  Enzymes and the Rate of Chemical Reactions Enzyme Activity Influencers (2) – Enzyme activity can also be influenced by inhibitors and activators Inhibitors decrease the activity of enzymes Two types: – Reversible - form weak bonds with enzymes – Irreversible – form covalent bonds with enzymes Activators increase the activity of enzymes. BIOL1010 and 14  Enzymes and the Rate of Chemical Reactions Enzyme Inhibitors – Competitive Inhibitors In this case, what would happen if you increased the concentration of the substrate? BIOL1010 and 15  Enzymes and the Rate of Chemical Reactions Enzyme Inhibitors – Non-competitive Inhibitors Enzymes regulated in this way are called allosteric enzymes (process = allosteric inhibition) BIOL1010 and 16  Enzymes and the Rate of Chemical Reactions Enzyme Inhibitors – Enzyme inhibitors are fairly common Synthesized naturally by plants and animals as defense Pesticides and herbicides – Target enzymes to inactivate them – Examples – organophosphates like malathion, “Roundup” Many medicines are enzyme inhibitors – Antibiotics, antidepressants, diuretics BIOL1010 and 17  Enzymes and the Rate of Chemical Reactions Allosteric Enzymes and Metabolic Pathway Regulation – Allosteric enzymes can be influenced by both inhibitors and activators – Isoleucine shuts down its own production by binding to first enzyme in pathway  enzyme shape changes  function inhibited – Negative feedback – Threonine dehydratase = allosteric enzyme BIOL1010 and 18