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Lipid synthesis

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Lipids

A group of organic compounds that are insoluble in water

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1. Long term energy storage

2. Protection against heat loss (insulation)

3. Protection against physical shock

4. Protection against water loss

5. Chemical messengers (hormones)

6. Major component of membranes (phospholipids)

Function of lipids

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Fatty acid synthesis

Fatty acid synthesis – Liver , adipose tissue & kidney

De novo synthesis

Chain elongation

Acetyl CoA

Palmitic acid (C16)

Cytosol

Mitochondria, Microsomes

C16- palmitic acid

C20- Arachidonic acid

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Stages

  1. Production of acetyl CoA
  2. Conversion of acetyl CoA to malonyl CoA
  3. Malonyl coA to Palmitic acid.

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1. Production of Acetyl CoA

Acetyl CoA

Acetyl CoA is the starting material for fatty acid synthesis

Glucose

Pyruvate

Fatty acids

Glycolysis

β-oxidation

Amino acids

Degradation

Acetyl CoA

Acetyl CoA

Mitochondria

Sources

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Transport of acetyl coA into cytosol

Mitochondria

Cytosol

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Transport of acetyl coA into cytosol

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2. Formation of Malonyl CoA

  • Acetyl CoA is carboxylated to malonyl CoA by the enzyme acetyl CoA carboxylase.
  • This is an ATP-dependent reaction & requires biotin for CO2 fixation.
  • Acetyl CoA carboxylase is a regulatory enzyme

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3. Synthesis of Palmitic acid

Fatty acid synthase

Malonyl coA

Palmitic acid

Multi step

process

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Fatty acid synthase

(Multi enzyme complex)

It has 7 enzymes & one Acyl carrier protein

Condensing unit

  • Initial substrate binding site
  • β-keto acyl synthase
  • acetyl transferase (AT)
  • malonyl transacylase (MT)

Reduction unit

  • dehydratase (DH),
  • enoyl reductase (ER),
  • β-keto acyl reductase (KR)
  • acyl carrier protein (ACP)

Releasing unit

  • release of synthesized

fatty acid

  • thio-esterase(TE)

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  • Acetyl CoA is transferred to ACP of FAS, by the enzyme acetyl tranacylase
  • The enzyme malonyl transacylase transfer malonate from malonyl CoA to ACP to form acetyl-malonyl enzyme.
  • Now fatty acid synthase has two group attached to it.
  • An acetyl group to cysteine –SH and malonyl group at ACP-SH.

Activation of Fatty acid synthase

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Elongation step

Condensation

Reduction

Dehydration

Reduction

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Condensation

Reduction

Dehydration

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Reduction

Further

Chain elongation

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Release of Palmitic acid

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Condensation

Reduction

Dehydration

Reduction

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Complete palmitic acid oxidation

7 NADH + 7 FADH2 + 8 acetyl-CoA in 7 cycles

One acetyl-CoA yields

3 NADH + 1 FADH2 + 1 GTP (=ATP) in TCA cycle

Eight acetyl-CoA yields

24 NADH + 8 FADH2 + 8 GTP (=ATP) in TCA cycle

Beta oxidation + TCA cycle

31 NADH + 15 FADH2 + 8 GTP (=ATP) in TCA cycle

Total ATP production

NADH 31 × 3 = 93 (Activation uses 2ATP)

FADH2 15 × 2 = 30

GTP 8 × 1 = 8

Total = 131. Net ATP = 131 - 2 = 129