enzyme inhibition by dr. ashok kumar jeppu

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DR.ASHOK KUMAR JEPPU BIOCHEMISTRY MANAGEMENT AND SCIENCE UNIVERSITY MALAYSIA 8/27/2010 Dr. Ashok KUmar J; ; Department of Biochemistry. MSU, Malaysia 1

TRANSCRIPT

DR.ASHOK KUMAR JEPPU

BIOCHEMISTRY

MANAGEMENT AND SCIENCE UNIVERSITY

MALAYSIA

8/27/2010Dr. Ashok KUmar J; ; Department of Biochemistry. MSU,

Malaysia1

8/27/2010 2Dr. Ashok KUmar J; ; Department of Biochemistry. MSU,

Malaysia

8/27/2010 3Dr. Ashok KUmar J; ; Department of Biochemistry. MSU,

Malaysia

Vmax

Km Km’ [S], mM

v

I

Vmax unchanged and Km increased

8/27/2010 4Dr. Ashok KUmar J; ; Department of Biochemistry. MSU,

Malaysia

1/[S]-1/Km

1/vo

1/ Vmax

Intersect at Y axis

8/27/2010 5Dr. Ashok KUmar J; ; Department of Biochemistry. MSU,

Malaysia

8/27/2010 6Dr. Ashok KUmar J; ; Department of Biochemistry. MSU,

Malaysia

8/27/2010 7Dr. Ashok KUmar J; ; Department of Biochemistry. MSU,

Malaysia

8/27/2010 8Dr. Ashok KUmar J; ; Department of Biochemistry. MSU,

Malaysia

8/27/2010 9Dr. Ashok KUmar J; ; Department of Biochemistry. MSU,

Malaysia

Non-competitive Inhibition

8/27/2010 10Dr. Ashok KUmar J; ; Department of Biochemistry. MSU,

Malaysia

[I] binds to free [E] or [ES] complex;

Increasing [S] can not overcome [I]

inhibition

E + S → ES → E + P

+ +I I

↓ ↓

EI + S →EI S

↑ ↑

8/27/2010 11Dr. Ashok KUmar J; ; Department of Biochemistry. MSU,

Malaysia

8/27/2010 12Dr. Ashok KUmar J; ; Department of Biochemistry. MSU,

Malaysia

8/27/2010 13Dr. Ashok KUmar J; ; Department of Biochemistry. MSU,

Malaysia

8/27/2010 14Dr. Ashok KUmar J; ; Department of Biochemistry. MSU,

Malaysia

8/27/2010 15Dr. Ashok KUmar J; ; Department of Biochemistry. MSU,

Malaysia

8/27/2010Dr. Ashok KUmar J; ; Department of Biochemistry. MSU,

Malaysia16

8/27/2010 17Dr. Ashok KUmar J; ; Department of Biochemistry. MSU,

Malaysia

Km

[S], mM

Vmax

I

Km’

Vmax’

8/27/2010 18Dr. Ashok KUmar J; ; Department of Biochemistry. MSU,

Malaysia

8/27/2010 19Dr. Ashok KUmar J; ; Department of Biochemistry. MSU,

Malaysia

8/27/2010 20Dr. Ashok KUmar J; ; Department of Biochemistry. MSU,

Malaysia

Difluro Methyl Ornithine(DFMO)-

DFMO inhibits ODC in trypanosomaMultiplication of trypanosoma is inhibited

Effective for the treatment of trypanosomiasis(Sleeping Sickness)

DFMO forms covalent complex with co-enzyme

(PLP) and amino acid residues of the enzyme

8/27/2010 21Dr. Ashok KUmar J; ; Department of Biochemistry. MSU,

Malaysia

Allopurinol

Alloxanthine

Aspirin acetylates a serine residue in the active center of cyclo-oxygenase

Prostaglandin synthesis is inhibited8/27/2010 22

Dr. Ashok KUmar J; ; Department of Biochemistry. MSU, Malaysia

5 - flurouracil

8/27/2010Dr. Ashok KUmar J; ; Department of Biochemistry. MSU,

Malaysia23

Allostearic “occupying another space”Allosteric site was first proposed by

Jacques Monod

Substances which bind to allostearic site can modify their activity – Allosteric effector

Allosteric effectorsSubstances that bind to allosteric site and

modifies the activity of the protein

8/27/2010 24Dr. Ashok KUmar J; ; Department of Biochemistry. MSU,

Malaysia

Binding of an allosteric effector induces conformational change in the enzyme

8/27/2010 25Dr. Ashok KUmar J; ; Department of Biochemistry. MSU,

Malaysia

Affects the activity of the enzyme

Activity of the enzyme increases

Activity of the enzyme decreases

Allosteric activator Allosteric inhibitor

An intermediate or a product of a metabolic pathway allosterically inhibits anenzyme

catalyzing earlier stepFeed back Allosteric Inhibition

E1 E2 E3 E4 E5 E6A B C D E F G

Aspartate TranscarbamoylaseInitial step of pathway which synthesize CTP

CTP acts as allosteric inhibitor

8/27/2010 26Dr. Ashok KUmar J; ; Department of Biochemistry. MSU,

Malaysia

Thank You

8/27/2010 27Dr. Ashok KUmar J; ; Department of Biochemistry. MSU,

Malaysia