enzymes hl Flashcards
Generation of heat energy by the reactions of metabolism
- Include the idea that heat generation is inevitable because metabolic reactions are not 100% efficient in energy transfer. Mammals, birds and some other animals depend on this heat production for maintenance of constant body temperature.
- Metabolic reactions often result in the release of heat energy. This is because the products of a reaction usually have less energy than the reactions. The additional energy is converted to heat.
- Birds and mammals use this energy to maintain a body temperature greater than their environment.
- Birds and mammals also show adaptations to heat generation to raise their basal metabolic rate above the external temperature.
- Brown fat cells in adipose tissue contains more mitochondria than white fat cells or any other body tissue. More energy can be generated through uncoupled respiration (without the production of ATP)
- Involuntary muscle contractions which result in shivering also generate more heat and raise the body temperature.
Intracellular and extracellular enzyme-catalysed reactions
Intracellular: Often inside organelles (e.g. mitochondria, nucleus) cytoplasm or bound to membranes where reactions are catalyzed by enzymes produced by free ribosomes in the cell. (glycolysis and the Krebs cycle)
Extracellular: Exoenzymes synthesized by the rER which are released from glands or specialized cells into the interior of an organ catalyzing the breakdown of larger macromolecules into monomers. (chemical digestion)
Cyclical and linear pathways in metabolism
- Use glycolysis, the Krebs cycle and the Calvin cycle as examples.
Metabolic pathways are chains or cycles of enzyme-catalysed reactions; the product of one reaction is the reactant in the next
Features
1. Most chemical changes happen not in one large jump, but in a sequence of small steps (called a metabolic pathway.)
2. Most metabolic pathways involve a linear chain of reactions.
3. Some metabolic pathways form a cycle. (The end product of one reaction that starts the rest of the pathway)
Allosteric sites and non-competitive inhibition
- Students should appreciate that only specific substances can bind to an allosteric site. Binding causes interactions within an enzyme that lead to conformational changes, which alter the active site enough to prevent catalysis. Binding is reversible.
- Enzyme inhibitors are chemical substances that reduce or prevent an enzymatic rxn from happening by blocking the enzyme
- Substrate and inhibitor are not chemically similar.
- The inhibitor binds to a different site from the active site (allosteric site)
- By binding with the enzyme, the inhibitor changes the conformation in the active site of the enzyme. Binding is reversible.
- The substrate may still be able to bind to the active site, but reaction may not take place or only at a slow rate.
- Heavy metal poisoning is an example of irreversible, non-competititive inhibition.
- Sarin, a nerve gas used in biological warfare works as a non-competitive irreversible inhibitor
Competitive inhibition as a consequence of an inhibitor binding reversibly to an active site
- Use statins as an example of competitive inhibitors. Include the difference between competitive and noncompetitive inhibition in the interactions between substrate and inhibitor and therefore in the effect of substrate concentration.
- Substrate and inhibitor are chemically very similar, so the inhibitor can bind with the same active site as the substrate.
- When an inhibitor binds with the enzyme, the site is occupied and no longer free for the substrate.
- As a result, the substrate cannot bind and the reaction (which is reversible) cannot take place.
- Statins are medicines that work by competitive enzyme inhibition to treat cardiovascular disease caused by cholesterol. Cholesterol is the build-up of fat and plaques in blood vessels, essentially contributing to heart disease.
- Statins bind to an enzyme which is used to synthesize cholesterol in liver cells, therefore preventing more production of it in the human body.
- Normally, angiotensin is a substance produced by an enzyme (ACE) which binds to receptors in the wall of arteries, inducing a constriction of blood vessels and an increase in blood pressure. People suffering from high blood pressure can be treated with inhibitors.
- ACE inhibitors inhibit the action of the enzyme helping to lower blood pressure increase blood to heart (opens coronary arteries/dilated)
Regulation of metabolic pathways by feedback inhibition
- Use the pathway that produces isoleucine as an example of an end product acting as an inhibitor.
- If in high enough quantities, isoleucine binds to the allosteric binding site on the enzyme threonine deaminase, preventing further binding of threonine to the active site.
- the rnx is reversible
Mechanism-based inhibition as a consequence of chemical changes to the active site caused by the irreversible binding of an inhibitor
- Use penicillin as an example. Include the change to transpeptidases that confers resistance to penicillin.
- Many antibiotics act by binding irreversibly to the active site by forming a covalent bond and inducing a permanent change. Penicillin binds to the bacterial enzyme transpeptidase. Bacteria use this enzyme to catalyze the formation of peptidoglycan cross-links in its cell wall.
- Without a functional enzyme the cell wall of the bacteria will receive holes in the cell wall and eventually force the bacteria to shed most if not all of its wall.
