This document summarizes the de novo synthesis of fatty acids. It discusses that fatty acid synthesis primarily occurs in the liver and lactating mammary glands using acetyl CoA, ATP, NADPH, Mn2+, and biotin. The first step is the production of cytosolic acetyl CoA from mitochondrial acetyl CoA. Acetyl CoA is then carboxylated to form malonyl CoA by acetyl CoA carboxylase. Fatty acid synthase is a multifunctional enzyme that catalyzes the remaining reactions. The major sources of NADPH required are the pentose phosphate pathway and conversion of malate to pyruvate in the cytosol. Palmitate, a 16 carbon

1. Department of Biochemistry, NGMC, Chisapani, Nepal
Tuesday, June 14,
2016
Rajesh Chaudhary
1
MBBS I
2nd.
Semester

2. Structure of fatty acids
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2016
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3. Some facts
De Novo Synthesis of Fatty acids
Large portion of fatty acid supplied in our body is through diet.
In adults, fatty acid synthesis occurs in primarily in liver and
lactating mammary glands and to lesser extent in adipose
tissue. (liver kidney, brain, lungs, mammary glands, adipose tissue)
Production utilizes Acetyl CoA, ATP, NADPH, Mn2+, and biotin.
First step in synthesis is transfer of acetate units from
mitochondrial acetyl CoA to the cytosol.
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2016
Rajesh Chaudhary
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4. Steps
1. Production of cytosolic Acetyl CoA.
2. Carboxylation of Acetyl CoA to form Malonyl CoA.
2.1. Short-term regulation of acetyl CoA carboxylase
2.2. Long-term regulation of acetyl CoA carboxylase
3. Role and significance of fatty acid synthase.
4. Major sources of the NADPH required for fatty acid
synthesis.
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2016
Rajesh Chaudhary
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De Novo Synthesis of Fatty acids

5. Steps
5. Further elongation of fatty acid chain.
6. Desaturation of fatty acid chain.
7. Storage of fatty acids as components of
triacylglycerols
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2016
Rajesh Chaudhary
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De Novo Synthesis of Fatty acids

6. 1. Production of cytosolic Acetyl CoA.
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2016
Rajesh Chaudhary
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Pyruvate Fatty acids
Ketone
bodies
Amino acids
Mitochondrial
Acetyl CoA Cytosolic
Acetyl
CoA

7. 1. Production
of cytosolic
Acetyl CoA.
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2016
Rajesh Chaudhary
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High amount of ATP
is required for fatty
acid synthesis.

8. 2. Carboxylation of acetyl
CoA to form malonyl CoA
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2016
Rajesh Chaudhary
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Short-term Vs Long-
term regulation of
acetyl CoA
carboxylase
Biotin is required
by carboxylase as
cofactor.

9. 3. Role and significance of fatty acid
synthase
Fatty acid synthase is a multifunctional, dimeric enzyme
which catalyzes the remaining reactions of fatty acid
synthesis.
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10. Palmitic acid and palmitate
Palmitate is a term for the salts and esters of palmitic acid.
It is the most common fatty acid found in animal, plants and
microorganisms.
Excess carbohydrates and proteins are converted to
palmitic acid.
It is the first fatty acid synthesized during fatty acid
synthesis.
Application: used to produce soaps and cosmetics.
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2016
Rajesh Chaudhary
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11. 4. Major sources of NADPH required for fatty
acid synthesis
Hexose monophosphate pathway (Pentose phosphate
pathway) is the major supplier of NADPH for fatty acid
synthesis – 2 NADPH is produced from each glucose
molecule that enters the pathway.
The cytosolic conversion of malate to pyruvate also
produces NADPH.
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2016
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12. Interrelationship
between glucose
metabolism and
palmitate
synthesis
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13. 4. Major sources of NADPH required for
fatty acid synthesis
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14. 5. Further elongation of fatty acid
chain
Palmitate: 16-carbon, full saturated long-chain length fatty
acid, is the primary product of fatty acid synthase activity.
Elongated further by addation of two carbon units in ER &
mitochondria.
Brain has additional capacity to elongate it to further more
– up to 24 carbons that is required for synthesis of brain
lipids.
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2016
Rajesh Chaudhary
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15. Synthesis of
triacylglycerol
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16. Storage of fatty acids as components of
triacylglycerols
Mono, di and triacylglycerols consists of one, two or three
molecules of fatty acid esterified to a molecule of glycerol.
TAG are slightly soluble in water and cannot form stable
micelles by themselves, they coalesce within adipocytes to
form oily droplets.
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2016
Rajesh Chaudhary
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17. Rajesh Chaudhary
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