BIOCHEMISTRY FATTY ACID SYNTHESIS

FATTY ACID SYNTHESIS

Doç. Dr. Salim NEŞELİOĞLU
PREPARED BY: Oğuz Ç.

De nova synthesis of fatty acids (TG, TAG) and triglycerides

Fatty acid (FA) synthesis is the creation of fatty acids from acetyl-CoA and NADPH through the action
of enzymes called fatty acid synthases.
This process takes place in the cytosol of the cell.
Most of the acetyl-CoA which is converted into fatty acids is derived from carbohydrates via the
glycolytic pathway.

Stages of FA Synthesis
1. Transfer of acetyl-CoA from mitochondria to cytosol.
- In fatty acid synthesis, the carbon skeleton of acetyl CoA is transported from the mitochondria to the
cytosol in the form of citrate. #lecturer said that keep it in mind
2. Synthesis of malonyl-CoA from acetyl-CoA #this point is important
3. Elongation cycle of FA synthesis.

Acetyl-CoA carboxylase is a biotin-dependent enzyme that catalyzes the irreversible carboxylation of

acetyl-CoA to produce malonyl-CoA
 BIOCHEMISTRY FATTY ACID SYNTHESIS

Cofactors in Fatty Acid

Biosynthesis
NADPH,

ATP,

Mn+2 (manganese),

Biotin,

HCO3- (Bicarbonate)

The reason for fatty liver due to protein deficiency

• Synthesized fatty acids in the liver are attached to each of the three carbons of the glycerol molecule.
They are called triacylglycerols or triglycerides.
• Very low-density lipoprotein (VLDL) is the major vehicle in the blood that carries triacylglycerol
synthesized in the liver to peripheral tissues for utilization.
• But in protein deficiency, lipoproteins cannot be synthesized and cannot enter the bloodstream.
• Thus, triglycerides accumulate in the liver and fatty liver (hepatic steatosis) occurs.
• Almost all fatty acids found in mammalian tissues are straight-chained, but fatty acids, found in nature
contain branched chains (eg phytanic acid, a vegetable fatty acid).
• Phytanic acid is a branched-chain fatty acid found in plants, generally.
• The presence of the 3-methyl group of phytanic acid prevents degradation by beta-oxidation.
• In a normal condition, first the methyl group of phytanic acid blocking beta oxidation in the
peroxisome is removed by alpha oxidation and then the rest is removed by beta oxidation.
• Refsum disease is the disease of phytanic acid accumulation in plasma and tissues due to its alpha
oxidation defect.
• In Refsum disease, neurological symptoms such as neuropathy, cerebral ataxia, night blindness are
observed.

Short Notes
• Free fatty acids are carried in the blood by albumin. However, most of the fatty acids (> 90%) are
transported by lipoproteins.
• As fatty acids enter the cell, they bind to the membrane-associated fatty acid-binding protein and
are transported from the cell membrane to the cytosol together with sodium (cotransport).
 BIOCHEMISTRY FATTY ACID SYNTHESIS

#Fatty acids synthesis takes places by combining AcetylCoA molecules. First, an AcetylCoA molecule
binds to phosphopantetheine arms of the fatty acid synthesis complex. Then AcetylCoa is transfarred
from phosphopantetheine arm to the sulfhydryl arm. The newly synthesized MalonilCoA is attached
to the free phosphopantetheine arm. The MalonilCoA molecule in the phosphopantetheine arm loses a
CO2 and the molecule with 2 Carbons formed. AcetylCoA and the sulfhydryl arm are attached to this
molecule. There isn't C with 4 C in the phosphopantetheine arm. The double bond on this compound
are reduced by using 2 NADPH. Finally,the compound with 4 Carbons formed is transferred to the
the sulfhydryl arm. The newly synthesized MalonilCoA is attached to the free phosphopantetheine
arm.And the new cycle is initiated to at 2 Carbons again. This cycle continues until palmitic acid with
16 Carbons is formed.

Sources of NADPH for FA Synthesis

1. Pentose phosphate pathway

2. Malic enzyme

3. Non-mitochondrial isocitrate dehydrogenase

NADPH is used at four locations

1. It is used in synthesis of fatty acids
2. It is used in antioxidant defense system in erythrocytes (Converts oxidized glutathione to reduced
glutathione)
3. It is used for detoxification of fat-soluble drugs
4. It is used as the coenzyme of NADPH oxidase enzyme in leukocytes (in the immune defense system).

✓ Fatty acid synthesis is a multi-step process performed by the fatty acid synthase enzyme complex,
which has phosphopantetheine and sulfhydryl arms.
✓ Fatty acid synthesis is carried out by means of cysteine amino acid containing sulfhydryl group.
✓ The first fatty acid synthesized in the body is always palmitate, a saturated fatty acid with 16 carbons.
In addition, various fatty acids can be formed from palmitate by elongation and desaturation reactions.
 BIOCHEMISTRY FATTY ACID SYNTHESIS

For the synthesis of a fatty acid with 16 carbons, the following

are used:
• 1 Acetyl-CoA

• 7 Malonyl-CoA

• 7 ATP

• 14 NADPH

When synthesizing a fatty acid with 16 carbons;

• Fatty acid synthesis starts with the carboxylation of acetyl CoA to malonyl CoA.

• The first two carbons of palmitate originate from acetyl CoA. The remaining carbons are occurred by
the repetitive condensation of two-carbon units derived from malonyl CoA.

Formation of various fatty acids from palmitate by elongation

and desaturation reactions
• The process of elongation and desaturation are carry out in the endoplasmic reticulum and
mitochondria.

• The mechanism in the mitochondria is a little different than cytosolic fatty acid synthesis and involves
the addition of two-carbon units directly from acetyl-CoA without the malonyl-CoA intermediate.

• However, the mechanism in the endoplasmic reticulum is the same as for cytosolic fatty acid synthesis
(addition of malonyl CoA).

• If there is a double bond after the 9-10th carbon in a fatty acid in the body, it means that this fat has
been taken with diet. Because there are no enzymes that will form a double bond after the 9-10th
carbon in humans.

• These fatty acids are called essential fatty acids.

• For example; linoleic acid (two double bound; 9th and 12th carbons), linolenic acid (three double
bound; 9th, 12th and 15th carbons)

Regulation of fatty acid synthesis

• While insulin activates fatty acid synthesis, anti-insulinogenic hormones suppress it.
• Anti-insulinogenic hormones are glucagon, adrenaline, growth hormone and
glucocorticoids.
• In general, insulin activates all synthesis reactions (such as fatty acid synthesis, glycogen synthesis,
cholesterol synthesis), while inhibiting all catabolic reactions (such as fatty acid oxidation).
 BIOCHEMISTRY FATTY ACID SYNTHESIS

Synthesis of triglycerides

• Glycerol-3-phosphate is the main source of triglycerides synthesis

• Glycerol-3-phosphate is obtained mainly in 2 ways

1. From glycerol

2. From dihydroxyacetone phosphate formed in glycolysis

• The structure formed when fatty acid is attached to the first 2 carbons of glycerol-3-phosphate is called
phosphatidic acid or phosphatidate.

• Triacylglycerol and glycerophospholipids are synthesized from phosphatidate.

salim_neselioglu@hotmail.com