- WELCOME TO PROTEIN AND ENZYMES PART 9.
AT THIS PART, WE'VE DEFINITELY SHIFTED INTO THE ENZYME PORTION
AND HERE WE'RE GOING TO LOOK AT WHAT INHIBITS ENZYMES.
LET US GET STARTED.
SO, WHAT ARE ENZYME INHIBITORS?
SO, LET US REMEMBER THAT ENZYMES ARE PROTEINS
THAT CATALYZE BIOCHEMICAL REACTIONS.
AND SO AN INHIBITOR THEN IS ANY COMPOUND OR ENVIRONMENTAL
CONDITION THAT PREVENTS THE ENZYME FROM PERFORMING
ITS FUNCTION WHICH IS CATALYSIS.
SO, THERE ARE TWO DIFFERENT TYPES OF INHIBITORS,
THERE ARE NONSPECIFIC, AND SPECIFIC.
SO, FOR RIGHT NOW WE'LL JUST FOCUS ON NONSPECIFIC.
SO, THIS MEANS THAT THEY'RE VERY LIKE THEY'RE VERY GLOBAL,
THESE ARE THINGS THAT AFFECT ALL ENZYMES.
AND SO, I'M SURE SEVERAL OF THESE CAN COME TO MIND
BECAUSE WE'RE TALKING ABOUT CATALYSIS OF REACTIONS
AND THINGS THAT WE KNOW THAT INFLUENCE REACTIONS
ARE TEMPERATURE AND PH.
SO, LET US LOOK A LITTLE MORE CLOSELY
AT THE EXACT CONSEQUENCES OF HOW TEMPERATURE AND PH
AFFECT ENZYMES.
SO, LET'S LOOK AT TEMPERATURE FIRST.
SO, IF WE THINK BACK TO COLLISION THEORY
AND WHAT'S GOING ON FOR REACTIONS TO OCCUR,
WE LEARN THAT INITIALLY, AS WE INCREASE THE TEMPERATURE,
WE'RE INCREASING KINETIC ENERGY, RIGHT?
SO, HERE'S TEMPERATURE ALONG THE X-AXIS
AND REACTION RATE ALONG THE Y-AXIS.
SO, AS WE INCREASE THE TEMPERATURE
AS WE WOULD EXPECT, WE INCREASE THE REACTION RATE
BECAUSE WE'RE BRINGING IN MORE KINETIC ENERGY.
SO, THERE'S MORE ENERGY AVAILABLE FOR INTERACTIONS
AND COLLISIONS BETWEEN REACTANTS,
AND IT ALLOWS THEM TO GET TO THE TRANSITION STATE.
SO, THAT'S NOT TOO SURPRISING. AN INCREASE IN TEMPERATURE
WILL INCREASE THE RATE OF A CATALYZED REACTION.
BUT UP TO A POINT, MORE IS NOT ALWAYS BETTER.
AT A PARTICULAR TEMPERATURE THOUGH, WE GET TO THE MAXIMUM
AND THEN ANY FURTHER INCREASE IN TEMPERATURE FORCES A DECREASE
IN THE REACTION RATE.
AND WHY IS THAT?
NOW WE HAVE TO THINK ABOUT THE STRUCTURE OF OUR ENZYME.
AND WHAT HAPPENS IS WE BEGIN TO DENATURE THE ENZYMES.
SO, IN THIS PORTION OF THE CURVE,
THE INCREASE IN TEMPERATURE,
THEN NOW THE ENZYME IS DENATURING, AT ELEVATED,
WE'LL JUST SAY, BECAUSE EVERY ENZYME HAS ITS OWN RANGE.
AND SO, THEN OVER HERE, THIS IS JUST CLASSIC COLLISION THEORY,
AS WE INCREASE THE TEMPERATURE WE INCREASE THE COLLISION
ENERGY.
AND SO WE GET TO THE-- OR WE CAN GET TO THE MINIMUM ENERGY
SO, WE HAVE MORE AND MORE OF OUR REACTANTS
AT ACTIVATION ENERGY.
OKAY. NOW, WE'LL LOOK AT THE OTHER NONSPECIFIC INHIBITOR
WHICH IS PH,
AND THINKING ABOUT ALL OF THE R GROUPS ON ENZYMES
AND HOW THEY INTERACT TO CREATE TERTIARY STRUCTURE
AND THAT SORT OF THING.
AND THAT'S VERY ELECTROSTATIC DEPENDENT.
WE CAN SEE THAT CATALYTIC ACTIVITY OF ENZYMES
DEFINITELY DEPENDS ON PH.
AND THERE'S TYPICALLY A WELL-DEFINED OPTIMUM POINT
FOR CATALYTIC ACTIVITY.
WELL, WITHIN THE BODY WE CAN THINK ABOUT PHYSIOLOGICAL PH
AT 7.4,
THERE ARE REGIONS OF OUR BODY THAT DO HAVE DIFFERENT PHs
PARTICULARLY FOR THE DIGESTIVE SYSTEM.
SO, IF WE LOOK AT PEPSIN, NOTICE WHERE ITS OPTIMUM PH IS,
REALLY CLOSE TO PH2.
SO, IMAGINE WHERE YOU THINK WE WOULD FIND PEPSIN,
WHERE IN OUR BODY DO WE HAVE SUCH A LOW PH?
SO, PEPSIN A DIGESTIVE ENZYME IN OUR STOMACH.
AND SO, WE RECOGNIZE, WITH THE STOMACH ACID,
OUR STOMACH, IS AT ABOUT PH2 OR SO.
SO, WE SEE THAT FOR THE ENZYME PEPSIN,
ITS OPTIMUM PH IS WHERE WE THINK ABOUT STOMACH ACID.
THEN CONVERSELY, LET'S LOOK AT TRYPSIN.
WHEN WE LOOK AT THE ENZYME TRYPSIN,
WE CAN SEE THAT ITS MAXIMUM IS VERY CLOSE TO A PH OF EIGHT.
SO, THEN IF WE THINK ABOUT IN OUR BODY
WHERE WE WOULD FIND THIS MORE BASIC CONDITION, RIGHT,
TRYPSIN WE FIND IN THE SMALL INTESTINE.
AND IT HELPS TO DIGEST VARIOUS SUBSTANCES.
SO, NOTICE THAT THE OPTIMUM PH IS SIMILAR TO THE PH
OF THE SMALL INTESTINE.
THAT'S PRETTY MUCH IT FOR NONSPECIFIC INHIBITION.
SO, NOW, WE'LL LOOK AT SPECIFIC INHIBITION MORE CLOSELY.
SO, WE'LL GO TO THE NEXT PAGE.
AND THERE ARE A VARIETY OF SPECIFIC INHIBITORS OUT THERE.
SO, WE'RE NOT GOING TO GO THROUGH ALL OF THEM
BUT WE'LL GO THROUGH SOME OF THE MAJOR ONES.
SO, THE FIRST I DO WHEN WE'RE THINKING ABOUT
SPECIFIC INHIBITION IS THERE IS
COMPETITIVE VERSUS NON-COMPETITIVE.
SO, HERE WE'RE BACK TO OUR ENZYME-SUBSTRATE, COMPLEX.
SO, THIS WOULD BE THE CATALYZED REACTION HAPPENING.
AND SO, IT'S VERY LITERAL.
SO, THE COMPETITIVE INHIBITOR IS INTERACTING
AT THE BINDING SITE WHERE WE WOULD NORMALLY SEE
THE SUBSTRATE.
SO, THAT'S A DIRECT COMPETITION FOR THE ACTIVE SITE
OF THE SUBSTRATE.
SO, COMPETITIVE IS A DIRECT COMPETITION.
HOWEVER, THERE IS AN ALTERNATE FORM OF COMPETITION
AND THAT'S THE NON-COMPETITIVE. AND THAT'S SHOWN RIGHT HERE.
SO, THIS BOX IS GOING WITH COMPETITIVE INHIBITION.
AND THEN FOR NON-COMPETITIVE, THERE IS A BINDING SITE
THAT THE SUBSTRATE DOESN'T CARE ABOUT, RIGHT?
THE SUBSTRATE DOESN'T CARE ABOUT THIS BINDING SITE AT ALL.
THIS IS WHERE THE NON-COMPETITIVE INHIBITOR
COMES IN.
SO, WITH NON-COMPETITIVE INHIBITION,
THE ACTIVITY OF THE ENZYME IS CONTROLLED BY THE BINDING
OF AN ACTIVATOR OR AN INHIBITOR AT A LOCATION
OTHER THAN THE ACTIVE SITE.
AND SO, WHEN THE NON-COMPETITIVE INHIBITOR IS PRESENT.
THE SUBSTRATE NO LONGER FITS.
THE SUBSTRATE NO LONGER FITS INTO, I GUESS, ITS ACTIVE SITE.
SO, WE CAN START TO RECOGNIZE, REMEMBERING THAT ENZYMES
ARE HUGE BIOLOGICAL MOLECULES. MANY OF THEM HAVE MOLAR MASSES
30, 50, 100,000 GRAMS PER MOLE.
SO, THIS IS A GOOD THING TO BRING INTO OUR AWARENESS
IS THAT AN ENZYME CAN HAVE MORE THAN ONE ACTIVE SITE.
THEN WE CAN LOOK A LITTLE MORE CLOSELY,
AND THESE ARE ALL INTERCONNECTED,
WE CAN LOOK AT FEEDBACK INHIBITION.
SO, AN IDEA OF FEEDBACK INHIBITION IS THAT
WE REGULATED ENZYMES ACTIVITY USING A PRODUCT OF A REACTION
LATER IN THE PATHWAY.
SO, TYPICALLY MOST BIOCHEMICAL PATHWAYS
WILL HAVE SEVERAL REACTIVE STEPS.
AND SO IF OUR BODY HAS 'A' IN HAND
AND WANTS TO PRODUCE Z, IT'LL GO THROUGH A SERIES,
SUBSTRATE 'A' WILL GO TO SERIES OF CHEMICAL TRANSFORMATIONS
TO GET TO OUR END PRODUCT.
BUT WHAT HAPPENS THEN IS ONE OF THE M PRODUCTS
BECOMES AN INHIBITOR FOR AN ENZYME EARLY IN THE PATHWAY.
AND THIS IS A COMMON STRATEGY BECAUSE THIS IS VERY EFFICIENT
FOR THE BODY.
TYPICALLY, WHEN WE HAVE FEEDBACK INHIBITION
ONE OF THE LATER PRODUCTS WILL INHIBIT EARLY IN THE PATHWAY
TO SAVE THE BODY RESOURCES OF MAKING THESE UNNECESSARY
INTERMEDIATES.
SO, WHEN--AND YOU CAN SEE THAT THIS IS VERY SELF-REGULATING.
SO, IF OUR BODY NEEDS Z, THE SWITCH GETS TURNED ON
THROUGH CHEMICAL COMMUNICATION AND 'A' STARTS PRODUCING Z.
ONCE THAT OUR BODY HAS ENOUGH Z, THEN IT SAYS,
"OKAY THERE'S ENOUGH OF ME," IT COMES BACK AND SAYS,
"YOU CAN STOP NOW, THERE'S ENOUGH."
SO, IT'S VERY EFFICIENT.
LET'S LOOK AT A SPECIFIC EXAMPLE.
AND MAYBE I SHOULD BE A LITTLE MORE EXPLICIT HERE,
SO, Z, RIGHT?
SO, SUFFICIENT Z WILL THEN CAUSE INHIBITION,
THEN Z TRIGGERS INHIBITION OF ADDITIONAL PRODUCTION.
SO, HERE'S AN EXAMPLE.
THE AMINO ACID THREONINE CAN BE CONVERTED INTO ISOLEUCINE.
AND THE FIRST ENZYME IN THIS PATHWAY IS THREONINE DEAMINASE
SO WE CAN IMAGINE SOMETHING IS HAPPENING WITH THE AMINE GROUP.
HOWEVER, ISOLEUCINE BONDS RIGHT TO A DIFFERENT SITE
ON THE ENZYME AND CHANGES THE CONFORMATION,
SO THAT THREONINE NO LONGER BINDS PROPERLY.
SO, HOW COULD WE DESCRIBE ISOLEUCINE?
SO, ISOLEUCINE IS A NON- COMPETITIVE INHIBITOR,
OF THREONINE DEAMINASE.
SO, IT COMES BACK AND THEN WE STOP THE PATHWAY.
SO NON-COMPETITIVE INHIBITION IS A FREQUENT MECHANISM
FOR FEEDBACK INHIBITION, SINCE WE HAVE CHANGES
IN THE STRUCTURE FROM THE FINAL PRODUCT
AND THE SUBSTRATE.
AND THEN THERE'S ONE MORE TERMINOLOGY
THAT WE SHOULD TALK ABOUT WITH NON-COMPETITIVE INHIBITION
AND THAT IS ALLOSTERIC CONTROL.
IN SOME WAYS, ALLOSTERIC CONTROL SEEMS VERY SIMILAR
TO NON-COMPETITIVE INHIBITION. I THINK THE MAIN THING HERE
IS THAT WE RECOGNIZE THAT IT COULD ALSO BE ACTIVATION.
SO, THIS PRETTY MUCH IS LIKE SYNONYMS,
AS MUCH AS I CAN TELL.
SO, LET'S LOOK HERE.
SO, THE DIFFERENCE IS WE'LL TALK ABOUT IT BEING
A POSITIVE REGULATOR, VERSUS A NEGATIVE REGULATOR.
SO, A POSITIVE REGULATOR IS GOING TO INCREASE CATALYSIS
AND VERY LOGICALLY A NEGATIVE REGULATOR
WILL DECREASE CATALYSIS.
SO, WE CAN SEE THAT IT'S BASICALLY
THE NON-COMPETITIVE INHIBITION.
SO, HERE IS OUR ACTIVE SITE FOR OUR SUBSTRATE
AND WE SEE THAT WITHOUT THE ALLOSTERIC REGULATOR,
THE ACTIVE SITE IS UNAVAILABLE.
AS SOON AS THE ALLOSTERIC REGULATOR COMES IN,
THEN WE SEE THAT WE'VE OPENED THE ACTIVE SITE
AND NOW THE SUBSTRATE CAN ENTER.
SO, NOW THE REACTION BEGINS.
SO, REACTIVITY BEGINS. OKAY.
CONVERSELY WITH THE NEGATIVE ALLOSTERIC REGULATOR CONTROL,
HERE WE COULD SEE THAT THE ENZYME IS QUITE HAPPY
TO INTERACT WITH THE SUBSTRATE, ALL IS WELL.
SO, RIGHT NOW WE WOULD HAVE REACTIVITY OCCURRING.
THE ENZYME CAN DO ITS THING, CATALYZING THE REACTION
FOR THE SUBSTRATE.
HOWEVER, ONCE THE NEGATIVE ALLOSTERIC REGULATOR COMES IN
AND INTERACTS WITH THE ENZYME, NOW THE SUBSTRATE CAN'T GET IN,
SO, REACTIVITY STOPS.
SO, THAT PRETTY MUCH WRAPS UP HOW WE INHIBIT AND REGULATE
ENZYMES.
SO, PLEASE TAKE SOME TIME NOW TO USE THESE CONCEPTS
TO SOLVE A FEW HOMEWORK PROBLEMS.