Fatty Acids

Properties of Fatty Acids

Caroxylic acids with long hydrophobic chain.

Even number of carbon atoms.
Saturated or unsaturated.
Alpha linolenic acid and linolenic acid are two essential fatty
acids.

Triacylglycerides

Stored in anhydrous state in adipose tissue.

A good source of energy, oxidized by many tissues.

Fatty Acid Synthesis

Occurs in well-fed state.

Under dietary and hormonal control.
Cytoplasmic pathway involving 2 major enzymes.
Occur in all tissues except RBC.
Excess stored in adipose tissue as triacylglycerides.
Acetyl-CoA is converted to citrate so it can be transported into
the cytoplasm.
Citrate converted to oxaloacetate and Acetyl-Coa.
Pyruvate is shuttled back into mitochondria.

Cytoplasmic Acetyl-CoA

Fatty acid synthesis.

Cholesterol Synthesis
Hormones, vitamin D, CoQ.

Steps:

Malonyl CoA made from Acetyl CoA with acetyl-CoA carboxylase.

Biotin

Covalently bonded to acetyl-CoA carboxylase.

Biotin is carboxylated at ring nitrogen which requires oxygen.
Carboxy group is transferred to Acetyl CoA to make Malonyl-CoA.
All carboxylation reactions use biotin as cofactor.

Acetyl CoA Carboxylase

Rate limiting step.

Require biotin and ATP hydrolysis.

Regulated by insulin and glucagon.

Regulated by AMPK and PP2A.
Dephosphorylated form is active.
Malonyl-CoA inhibits fatty acid oxidation.
AMPK inactivate carboxylase.
PP2A activate carboxylase.

Steps:

Acetyl-CoA + Malonyl CoA Butyryl + CO2

Malonyl CoA + fatty acid.
Carbonyl group reduced by 2 NADPH.
Thioesterase release C16 (palmitic)

Fatty Acid Synthase

Requires 7 cycles.
1 acetyl-CoA +7 Malonyl CoA
Final product is palmitic acid.
Enzyme bound cofactor 4PP made from pantethenic acid.
4PP is bound to Acyl Carrier Protein site.

Fatty Acid Elongation

Similar to FAS.
2 carbons added per cycle.
Cytoplasm pathway- Malonyl-CoA substrate.
Mitochondria pathway- Acetyl-CoA substrate.
Reducing equivalents come from NADH or NADPH

Desaturase

Cis double bonds are created by stearoyl CoA desaturase in the

ER.

Triglyceride Synthesis

Occur in well fed state.

3 carbon backbone from glycerol-3-P or DHAP.
Fatty acids from fatty acyl-CoA.
Common pathway for phosphoglyceride synthesis.
3C backbone phosphatidic acid 1,2-Diacylglycerol
triacylglycerol.