12/26/2011

BIOCATALYSIS
14.1: Properties of enzymes and mechanisms of actions

14.2: Cofactors

14.3: Inhibition

BIOCATALYSIS
Power point@lecture Slides Are Prepared By Biology Lecturer, KMPk

14.4: Enzyme Classification according to common name and IUB

PREVIOUS LESSON
Factors That Affect The Enzymatic Reaction.

PREVIOUS LESSON

PREVIOUS LESSON
Cofactor?
Types : Activator (Metal ions) Coenzyme Prosthetic group Functions: - Assist in forming the enzyme-substrate complex - withdraw electrons from the substrate.

OBJECTIVES
At the end of this subtopic, students should able to : Explain the roles and types of inhibitors.

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What are inhibitors?

A

Inhibitor
Usually specific. Work at low concentrations. They block the enzyme but they do not usually destroy it. Many drugs and poisons are inhibitors of enzymes in the nervous system. E.g Nerve gases Cyanide Pesticides
2008 Paul Billiet ODWS

substance that binds to an enzyme and decreases its activity.

(Raven and Johnson. Biology 9th edition. McGrawHill)

Any

molecule which acts directly on an enzyme to lower its catalytic activity.

(David Hames and Nigel Hooper. Biochemistry 3rd edition.)

TYPES OF INHIBITORS
Enzyme inhibition may be of two main types: Reversible Inhibition Competitive Inhibitor Noncompetitive Inhibitor Irreversible Inhibition

COMPETITIVE INHIBITOR
Has close structural similarities to the normal substrate. Inhibitor & substrate compete for active site. Bind reversibly to the active site (loosely bind).

COMPETITIVE INHIBITOR
Effect is temporarily to the enzyme. Enzyme can be reused again (do not destroy and do not denatured). Causes No Permanent Damage to the enzyme .

EXAMPLE OF COMPETITIVE INHIBITOR

Succinate
Succinate dehydrogenase CH2COOH CH2 CH2COOH COOH Malonate
(Inhibitor)
2008 Paul Billiet ODWS

Fumarate + 2H++ 2e-

COOH

CHCOOH

CHCOOH

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NONCOMPETITIVE INHIBITOR
How do we overcome inhibition of enzymes? competitive
Shape of inhibitor is NOT SIMILAR to the shape of substrate. Inhibitor will DO NOT directly compete with the substrate to bind to the enzyme at the active site.

Reversible by increasing concentration of substrate. It out competes inhibitor for active site on enzyme.

NONCOMPETITIVE INHIBITOR
Allosteric means other site Active site
Substrate cannot fit into the active site

NONCOMPETITIVE INHIBITOR
Inhibitor binds to site other than active site. Allosteric site (Regulatory site)

Allosteric site
Inhibitor fits into allosteric site

Allosteric inhibitor regulation of enzyme function. keeps enzyme inactive.

2008 Paul Billiet ODWS

The allosteric site the enzyme on-off switch

Active site Substrate fits into the active site E Allosteric site empty

NONCOMPETITIVE INHIBITOR
When the inhibitor is present it fits into its site. Causes enzyme (active site) to change shape. (Conformational change).
E

Conformational change
Substrate cannot fit into the active site

Inhibitor molecule is present Inhibitor fits into allosteric site

The substrate cannot bind with the substrate.

The inhibitor molecule is absent

2008 Paul Billiet ODWS

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NONCOMPETITIVE INHIBITOR
When the inhibitor concentration diminishes the enzymes conformation changes back to its active form.

NONCOMPETITIVE INHIBITOR

(Solomon. Biology 8th edition. Page 167.Thompson Learning Academic Resources)

EXAMPLE NONCOMPETITIVE INHIBITOR

Negative feedback : End point or end product inhibition Example: synthesis of amino acid, isoleucine from amino acid, threonine.

NONCOMPETITIVE INHIBITOR
Isoleucine becomes the

allosteric inhibitor of the first step in the pathway. As product accumulates it collides with enzyme more often than substrate does.

NONCOMPETITIVE INHIBITOR
The reaction slows down. When the inhibitor(product:isoleucine) concentration diminishes . Enzymes conformation changes back to its active form. This is NOT COMPETITIVE inhibition but it is REVERSIBLE.

NONCOMPETITIVE INHIBITORS

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QUESTIONS
Dont be inhibited! Ask Questions!
QUESTION 1 Organic cofactors that necessary for the catalytic power of enzymes are called A. reactant B. coenzymes C. holoenzymes D. Prosthetic group
2007-2008

QUESTIONS
QUESTION 2 Which of the following statements are true (T) or false (F)? a) Cofactors can be inorganic and oganic substances ( ) b) An enzyme without a cofactor called a holoenzymes ( )

QUESTIONS
QUESTION 3 What is an enzyme inhibitor? A. It is a molecule that enhances the energy of activation. B. It is a molecule that enhances the activity of enzyme. C. It is a molecule that interferes with the energy of activation. D. It is a molecule that interferes with the activity of an enzyme.

NEXT LECTURE
14.3 Inhibition
Irreversible inhibition

14.4 Enzyme Classification