SCH 511 Biosynthesis of Fatty Acids

[Pages:68]SCH 511

Biosynthesis of Fatty Acids

Source b-oxidation of FA Glycolysis of glucose

O

S CoA Acetyl CoA

O nH

O

O

CoA Malonyl CoA

S

Carboxylation of

O

acetyl CoA

H3C CH2 CH2 n-1 S CoA

Saturated thioesters

Saturated fatty acids

Dr. Solomon Derese

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SCH 511

The processes of fatty acid biosynthesis are known to be catalyzed by a multienzyme complex known as Fatty Acid Synthase (FAS).

Fatty acid synthase is arranged around a central Acyl Carrier Protein (ACP), which contains a protein bound pantetheine chain [Condensing Enzyme (HSEcondensing)] similar to the long chain of Coenzyme A, with six distinct catalytic centers.

Dr. Solomon Derese

39

O O

HS N N H H HO

O-

Ser

OPO

O FAS

ACP

SCH 511

O HS

N H

Dr. Solomon Derese

NH2

O N

O-

O-

OPOPO

N

N O

N N

O

O

H

HO

OH

Coenzyme A

O -O P O

-O

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Dr. Solomon Derese

SCH 511 41

pantetheine chain

SCH 511

Fatty Acid Synthase (FAS) SH SH

AT CE

MT

ACP

TE

KR

AT= Acetyl transferase MT= Malonyl transferase CE= Condensing enzyme

Dr. Solomon Derese

ER

DH

ACP= Acyl Carrier Protein KR= Keto Reductase ER= Enoyl Reductase

DH= DeHydratase TE= ThioEsterase

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SCH 511

Before acetyl CoA and malonyl CoA can be used in biosynthetic reactions, they have to be attached to the fatty acid synthase .

In this reaction the ? SCoA group of acetyl CoA and malonyl CoA are substituted by the thiol groups (SH) of HSEcondensing and ACP, respectively, of FAS.

The thiol groups are behaving as nucleophiles and the SCoA group as a leaving group in a nucleophilic acyl substitution reaction.

Dr. Solomon Derese

43

SCH 511

Once they are anchored to the fatty acid synthase, a carbon-carbon bond formation reaction occurs.

Acetyl-CoA and malonyl-CoA themselves are not involved in the condensation step: they are converted into enzyme-bound thioesters, Acetyl-SEcondensing and Malonyl S-ACP, respectively.

Dr. Solomon Derese

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SCH 511

The intermediates in fatty acid synthesis are

covalently linked to the Acyl Carrier Protein (ACP).

Dr. Solomon Derese

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