First discovered by Feodor Lynen. Also known as Lynen’s spiral.

It is not a reversal of oxidation. Cellular site: Cytoplasm Organ involved: Liver , kidney, adipose

tissue, brain and mammary gland. Immediate precursor: Acetyl CoA. Co-enzyme required: NADPH. The major fatty acid synthesized is

palmitic acid.

Glucose Pyruvate Fatty acid oxidation Ketone bodies Acetyl CoA Amino acids

HMP Shunt Malic enzyme Malate Pyruvate

NADP+ NADPH + H+

1. Transport of acetyl CoA2. Formation of Malonyl CoA3. Reactions catalyzed by fatty acid

synthetase complex.

Fatty acid/Pyruvate/amino acid

Citrate Synthase

Citrate transport

er

Transporter

Transporter

Malic enzymeMalic

enzyme

Acetyl CoA

Acetyl CoA

Citrate Lyase

MITICHONDRIA CYTOSOL

Oxaloacetate Citrate Citrate

Oxaloacetate

Malate

PyruvatePyruvate

Malate

NADHNAD

NADP

NADPHNADPH

NADPHNADH

NAD

ATP ADP+Pi

Fatty acid Synthesis

Acetyl CoA carboxylase is rate limiting enzyme.

Biotin is cofactor of the enzyme which is non-covalently bond to enzyme.

Acetyl CoA CarboxylaseAcetyl CoA + CO2 Malonyl CoA ATP Biotin ADP + Pi

The enzyme complex catalyzes the further steps of fatty acid synthesis.

It is a dimer consisting of 2 identical subunit. Each subunit consists of 7 different enzymes

and Acyl carrier protein(ACP). The SH group of 4’phosphopantetheine of

the ACP of one monomer is in close proximity to the SH group of cysteine residue of the ketoacyl synthase of other monomer.

De-

Condensing

Unit

Reducing unit

Releasing unit

Enoyl reductase

Dehydratase

Dehydratase

Enoyl reductase

KS

AT ERDH

KRACP TE

MT

TEACP

KRDH MT

AT

KS

ER

Subunit Division

FUNCTIONAL

CysSH

SH4’phospho pantethein

e

SHCys

4’phospho pantethein

eSH

A

ß-Hydroxyacyl-C0A

ß-Hydroxyacyl-ACP

Mitochondria Cytosol

Step2A: Transfer of the acetyl group to cysteinyl SH group of Ketoacyl synthase.

Step2B: Transfer of the Malonyl group to SH group of ACP.

Step3: Condensation of acetyl and malonyl group to from acetoacetyl-ACP.

Step4: Reduction Step5: Dehydration Step6: Reduction and formation of Butyryl-S-ACP

Cycling of reactions: Butyryl group is transferred to the SH

group of condensing enzyme in other monomer. A molecule of Manonyl will bind to SH group of ACP in other monomer.

The sequence of reactions(3 to 6) are repeated 6 times for the synthesis of Palmitic acid(16C).

Tioesterase releases palmitate from multienzyme complex.

Denovo synthesis of fatty acid in lactating mammary gland forms medium chain fatty acids{ Capric acid(10C) and Lauric acid(12C)}.

Palmitate is precursor for other long chain fatty acids.

Short term regulation 1. Allosteric regulation 2.Covalent modificationLong term regulation1.Hormonal regulation 2.Dietary regulation Induction/Repression

Citrate

Acetyl CoA

Malonyl CoA

Palmitic acid

Acetyl CoA Carboxylase

+

-

Acetyl CoA Carboxylas

e(Active)

Acetyl CoA Carboxylase

(Inactive)

Insulin

+Protein Phoshatase

P

Glucagon/ Epinephrine

+ ATPADP

Pi

Protein kinase

Covalent modification

High Carbohydrate

DietLow Fat Diet

Insulin(induction)

Synthesis of all enzymes of fatty acid biosynthesis

(repression)High Fat Diet

GlucagonLow Carbohydrate

Diet

+

-