How does Cyanide work? Controlling Enzyme Function

METABOLIC PATHWAYS So far we have looked at a single enzyme promoting a single reaction A B In reality, groups of enzymes catalyze multiple chemical reactions in a metabolic pathway A B C D The product of one reaction becomes the immediate substrate for the next enzyme and is rapidly consumed E1 E2E3

These pathways of enzyme-catalyzed steps ensure specific outcomes for the needs of the cell Making the chemical building blocks (ex. amino acids) of the cell Harnessing energy from food and sunlight The enzymes involved in many of the multi-step pathways that are so common in metabolism are located close together in the mitochondria The compartmentalization of enzymes also contributes to controlling enzyme function

ENZYME REGULATION Enzyme function is controlled by molecules that Mask Blockthe active site Alter When the molecule increases the productivity of the enzyme, it is an activator When the molecule slows down or prevents an enzyme from doing its work, it is called enzyme inhibition The molecule that interrupts the enzyme is the inhibitor There are two main kinds of inhibition: Competitive and Non-competitive

COMPETITIVE INHIBITION Competitive inhibitors bind reversibly to the active site and block the desired substrate from binding to the enzyme E + S  ES  E + P E + I  EI The metabolic reaction is halted until the inhibitor is removed In extreme cases, the inhibitor binding is permanent Eg. Cyanide is an inhibitor that binds IRREVERSIBLY to the enzyme

COMPETITIVE INHIBITION

NON-COMPETITIVE INHIBITION In non-competitive inhibition, the inhibitor binds to a regulatory site (away from the active site) on the enzyme, causing a change in shape which prevents the substrate from binding to the active site  alters the active site rather than blocks it

ALLOSTERIC REGULATION Activator and inhibitor molecules that bind to the allosteric site site on an enzyme that can be bound by other molecules to manage the enzyme’s activity – enzyme changes shape when filled oActivators open up and stabilize the active site to receive substrates oInhibitors close it up The change in shape causes the activity (effectiveness) of the enzyme to be either increased or inhibited

A molecule that increases enzyme activity in this way is called an allosteric activator When it inhibits enzyme activity it is called an allosteric inhibitor

A CLOSER LOOK AT CYANIDE Cyanide refers to a compound that contains a cyano group C ≡ N Most are highly toxic (it is the cyanide anion CN - that is responsible for the toxicity) The cyanide anion binds irreversibly to the enzyme Cytochrome C Oxidase Shuttles electrons in the Electron Transport Chain Pathway is disrupted Cells are no longer able to aerobically produce ATP Any tissue that produces ATP aerobically will be affected Central nervous system, heart In the end, the cells aren’t receiving enough oxygen, and die from cyanide poisoning This is irreversible competitive inhibition! Initial effects of poisoning - headache, faintness, vertigo, excitement, breathing difficulty, increased heart rate, and hypertension Later effects include coma, convulsions, paralysis, respiratory depression, pulmonary edema, arrhythmias, bradycardia, and hypotension, death Cyanide is rapidly absorbed from the stomach, lungs, mucosal surfaces, and unbroken skin