fatty acid synthesis

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

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Page 1: Fatty acid synthesis

Department of Biochemistry, NGMC, Chisapani, Nepal

Tuesday, June 14,

2016Rajesh Chaudhary

1

MBBS I

2nd.

Semester

Page 2: Fatty acid synthesis

Structure of fatty acids

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2016Rajesh Chaudhary

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Page 3: Fatty acid synthesis

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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2016Rajesh Chaudhary

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Page 4: Fatty acid synthesis

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.

Tuesday, June 14,

2016Rajesh Chaudhary

4De Novo Synthesis of Fatty acids

Page 5: Fatty acid synthesis

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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2016Rajesh Chaudhary

5De Novo Synthesis of Fatty acids

Page 6: Fatty acid synthesis

1. Production of cytosolic Acetyl CoA.

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2016Rajesh Chaudhary

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Pyruvate Fatty acidsKetone

bodiesAmino acids

Mitochondrial

Acetyl CoA Cytosolic

Acetyl

CoA

Page 7: Fatty acid synthesis

1. Production

of cytosolic

Acetyl CoA.

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2016Rajesh Chaudhary

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High amount of ATP

is required for fatty

acid synthesis.

Page 8: Fatty acid synthesis

2. Carboxylation of acetyl

CoA to form malonyl CoA

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2016Rajesh Chaudhary

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Short-term Vs Long-

term regulation of

acetyl CoA

carboxylase

Biotin is required

by carboxylase as

cofactor.

Page 9: Fatty acid synthesis

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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2016Rajesh Chaudhary

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Page 10: Fatty acid synthesis

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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2016Rajesh Chaudhary

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Page 11: Fatty acid synthesis

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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2016Rajesh Chaudhary

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Page 12: Fatty acid synthesis

Interrelationship

between glucose

metabolism and

palmitate

synthesis

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Page 13: Fatty acid synthesis

4. Major sources of NADPH required for

fatty acid synthesis

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Page 14: Fatty acid synthesis

5. Further elongation of fatty acid

chainPalmitate: 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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Page 15: Fatty acid synthesis

Synthesis of

triacylglycerol

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Page 16: Fatty acid synthesis

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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Page 17: Fatty acid synthesis

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