Fatty acid biosynthesis (19)

What is the output of β-oxidation?

Acetyl-CoA + FADH₂ + NADH

Under which conditions is FA synthesis necessary?

1. Cell division initiation

2. After a glucose-rich meal (excess is converted)

3. After a fructose-containing meal (bypass PFK1 control)

Where does FA synthesis happen?

Cytosol

How is acetyl-CoA transported to the cytosol?

Citrate shuttle

Describe the mechanism of action of the citrate shuttle (5)

1. NADH accumulates in the mitochondria

2. CAC stops

3. Citrate accumulates in mitochondria

4. Acetyl-CoA is converted to citrate = more citrate

5. a) FA synthesis b) oxaloacetate synthesis

C

Citrate lyase role

Citrate into Acetyl-CoA or Oxaloacetate

Citrate synthase role

Acetyl-CoA into Citrate

3 steps of palmitate synthesis

1. Synthesis of malonyl-CoA

2. Coupling to ACP

3. Elongation

Which enzyme converts Acetyl-CoA (2C) into Malonyl-CoA (3C)?

ACC (carboxylase)

Role of the ACC

Addition of a 1C molecule : CO₂ from biotin (same as PEP synthesis)

What is the activation step of FA synthesis?

Addition of ACP to malonyl-CoA and acetyl-CoA

What is transacylase’s role?

To couple acetyl-CoA and malonyl-CoA with ACP (further acetyl with KS)

Why are those molecules added?

To be able to bind to the fatty acyl sythase domains

When are the NADPH molecules used?

For the reduction steps

What molecule is added repetitively?

Malonyl-CoA -1carbon

Allosteric regulation of ACC

1. Citrate (+) : when plenty of energy we don’t use

2. Fatty acids (-) : product inhibition

Hormonal regulation of ACC

1. Insulin (+ partly active (-P)): glucose uptake = more acetyl-CoA

2. Glucagon (-): PKA-mediated phosphorylation

How do we make longer FAs (>16C)?

1. Palmitate synthesis

2. Add 2C at a time by using acetyl-CoA

How do we make unsaturated FAs?

Use 4 terminal desaturases (Δ9,6,5,4)

What makes FAs unsaturated beyond Δ9 essential FAs (linoleic and linolenic acids)?

The fact that mammals do not have desaturases beyond Δ9

What are prostaglandins and leukotrienes in relation to linolenic acid?

They derive from arachidonic acid which derives from linolenic acid

What are NSAIDs?

They (COX1/COX2) inhibit the conversion of arachidonic acid into those highly biactive molecules