MULTIPLE ENZYME COMPLEXES

Dr. Tijani A. S.

Learning objectives

This topic exposes the students to:

Multienzyme complexes and where they are found

Give examples of multienzyme complexes

Composition of some multienzyme complexes

Their mechanisms of actions

Multienzyme Complex

In a number of metabolic pathways, several enzymes which catalyze different stages of

the process have been found to be associated non-covalently, giving a multienzyme

complex.

The proximity of the different types of enzymes increases the efficiency of the

pathway; The overall reaction rate is increased with respect to catalysis by

unassociated units, and Side reactions are minimized.

In some cases molecular mechanisms have been identified for the transfer of

metabolites from one enzyme to the next within the complex.

Multienzyme complex is the structural and functional entity that is formed by the

association of several different enzymes which catalyze a sequence of closely

related reactions.

A multi enzyme complex is a protein possessing more than one catalytic domain

contributed by distinct parts of a polypeptide chain or by distinct subunits.

The regulation of this enzyme complex illustrates how a combination of covalent

modification and allosteric regulation results in specific regulated flux through a

metabolic step.

Multienzyme Complex Examples include:

(1) Pyruvate dehydrogenase complex (PDHC)

(2) Pyruvate carboxylase

(3) Fatty acid synthase

Pyruvate Dehydrogenase Complex (PDHC)

This multienzyme complex contains:

3 enzyme subunits and 5 coenzymes and other proteins.

The pyruvate dehydrogenase complex catalyzes the oxidative decarboxylation of

pyruvate to acetyl CoA. It is an organized assembly of 3 different catalytic subunits

of this complex enzyme. The reaction catalyzed is summarized thus,

Pyruvate + CoASH + NAD+ → CO₂ + Acetyl CoA + NADH + H+

It has coenzymes namely, CoA, lipoamide, NAD, thiamine PPO₄ and FAD.

ENZYME ABBREVIATION

NO OF

CHAINS

COENZYME

REACTION

CATALYSED

Pyruvate Dehydrogenase

Component

E1

24 Thiamine pyrophosphate (TPP) Decarboxylation of pyruvate

(provides a carbanion for

nucleophilic attack on the

substrate)

Dihydrolipoyl Transacetylase E2 24 Lipoamide, Coenzyme A

(CoASH)

Oxidation of carbon 2 units

(transfers substrate to

coenzyme A, retains

hydrogen)

Dihydrolipoyl Dehydrogenase

E3 12 Flavin adenine dinucleotide

(FAD), Nicotinamide adenine

dinucleotide (NAD+)

Regeneration of the oxidized

form of Lipoamide

(transfers H2 from lipoamide

to NAD+)

Composition of Pyruvate Dehydrogenase Complex (PDHC)

Table showing structural composition of PDHC from E. coli

Mechanism of Action of Pyruvate Dehydrogenase Complex

There are four steps in the conversion of pyruvate to acetyl CoA, which are catalyzed

by three different catalytic subunits of the enzymes:

1. Decarboxylation of pyruvate after its combination with TPP

(thiamine pyrophosphate) in a reaction catalyzed by E1 (pyruvate dehydrogenase)

2. Two steps of the conversion are catalyzed by E2 (dihydrolipoyl transacetylase)

enzyme:

oxidation of the 2-carbon (acetyl) unit, which is transferred to the lipoamide

prosthetic group of the enzyme, giving an acetyllipoamide group

transfer of the acetyl group from the lipoamide to CoA, giving acetyl CoA

3. Finally, E3 (dihydrolipoyl dehydrogenase) regenerates the oxidized form of

lipoamide. This involves the FAD prosthetic group. That is dihydrolipoyl

dehydrogenase transfers the H2 that was retained in the preceding steps to NAD+

Mechanism of Action of Pyruvate Dehydrogenase Complex

Fatty Acid Synthase

Mechanism of Action of Fatty Acid Synthase Complex

References

Biochemical pathways. An atlas of biochemistry and molecular biology. 2nd

Edition. John Wiley J. & Sons, Inc. 2012 by Michal G. and Schomburg D.

Principles of Biochemistry. 5th Edition. Pearson, 2012 by Moran L.A., Horton

H.R., Scrimgeour K.G., Perry M.D.

Principles of biochemistry. 6th Edition. W.H. Freeman and Company, 2012 by

Nelson D.L., Cox M.M. Lehninger.

. Harper’s illustrated biochemistry. 30th Edition. McGraw-Hill Education, 2015 by

Rodwell V.W., Bender D.A., Botham K.M., Kennelly P.J., Weil P.A

Biochemistry. 4th Edition. John Wiley J. & Sons, Inc. 2011 by Voet D. and Voet J.D.

Molecular and cellular enzymology. Springer, 2009 by Yon-Kahn J., Hervé G.

Notes on multienzyme complex by Ashwathi P

Pyruvate dehydrogenase complex by Christine Hrycyna

THANK YOU