Fatty Acid Synthesis

Where can FA biosyntehsis come from?

1. glucose --> pyruvate --> acetyl coa

• glycolysis in cytosol

• PDH in mitomatrix

2. beta-oxidation

• problem acetyl-coa is in matrix and sythesis occurs in cytosol and requires acetyl co-a

What do we do about the beta oxidation acetyl coa problem?

acetyl coa must be exported out of the mito by a tricarboxylate transport system since the inner membrane is impermeable

how is acetyl coa transported

in the form of citrate

When ATP is low, what happesn to acetyl-coa?

acetyl co is stored as TAGs
- requires Malonyl-CoA

Malonyl-CoA

- the 3c intermediate that is derived from acetyl0coa (activated)

What catalyzes the reaction from acetyl-coa to malonyl-coa

Acetyl-CoA carboyxlase
- requires biotin
- first commited step of FA synthesis

What is the condensation, reduction, dehydration, reduction catalyzed by?

Fatty acid sythase catalyzes the cycle, which in mammals is a multifunctional polytide with 7 domains

What is created from FA synthesis?

Palmitate, which is a saturated fatty acid, no intermediates are released

what does fa sythesis catalyze

4 step series reaction of ketone to alcohol to alkene to alkane

• at start of condensation of malonyl-coa and acetyl-coa growing chain opposite of beta oxidation

What does condensation of malonyl-coa and acetyl-coa require?

-Acyl carrier protein (ACP) a shuttl ethat holds the system together

ACP

-shuttle that holds system together -tether -holds growing fa chain to fa synthase, while carrying the intermeidate from one active site to the other. connects FA via thioester linkage

• at the end thioester bond is hydrolyzed and palmiatate is released from enzyme

• process drive by activation of acetyl-coa as malonyl-coa -nadph can be regenrated via pentose phosphate pathway

What can happen to palmitate?

• Can be made longer with elongases, which add 2c units from acetyl coa

• can make unsat fa with desaturases