FA breakdown + synthesis

steps for beta ox.

1. acyl-CoA synthetase

2. acyl-CoA dehydrogenase

3. enoyl-CoA hydratase

4. hydroxyacyl dehydrogenase

5. beta-ketoacyl thiolase

acyl-CoA synthetase

• this step is needed to activate the FA, since it is chemically inert

• addition of CoA into FA

• molecule will then be transported to mitochondria through a shuttle

Carnitine Antiport

• CPTI adds carnitine to FA-CoA, loses SCoA group

• complex diffuses through mitochondria

• CPTII releases FA-CoA from carnitine, SCoA group restored

• antiporter brings carnitine back out of the mitochondria for reuse

acyl-CoA dehydrogenase

• oxidation of alpha and beta carbons

• create double bond between alpha and beta carbons

• C=C makes it easy for water to attack later on

enoyl-CoA hydratase

• enzyme deprotonates H2O to make -OH (nuc group)

• strong base attacks double bond, later C=C is removed

hydroxyacyl dehydrogenase

• removes -OH group

• molecule becomes a beta-keto acid (two oxygens doubly bonded to carbons)

beta-ketoacyl thiolase

• cleave bond by attacking beta carbon

• forms acetyl-CoA and FA-CoA molecules (FA-CoA can continue cycle to generate more Acetyl-CoA)

odd-numbered fatty acid breakdown

• will yield x amounts of acetyl-CoA

• will yield 1 propionyl-CoA

Propionyl-CoA processing enzymes

• propionyl-CoA carboxylase = ADD CO2

• methyl malonyl-CoA epimerase = make R config.

• methyl malonyl mutase = move CO2, succinyl-CoA

What’s the end goal of processing propionyl-CoA?

make succinyl-CoA to bring to CAC

draw triacylglycerol/triglyceride structure

Precursor for FA synthesis

malonyl-CoA

Malonyl-CoA structure

Synthesis of Malonyl-CoA

• acetyl-CoA carboxylase, biotin co-factor

• add CO2 to acetyl-CoA molecule = malonyl-CoA

• rxn uses 1 ATP

FA synthase

• enzyme responsible for creating FA chain

• multiple active sites

• domains: KS, KR, DH, ER, MAT, TE, ACP

FA Synthesis steps overview

1. KS

2. KR

3. DH

4. ER

KS domain

• condensation rxn

• release of CO2 group

KR domain

• reduce beta-keto group

• one of the C=O becomes C-OH

DH domain

• dehydrate

• release H2O to create carbon double bond

ER domain

• reduction of double bond

ACP domain

• attach point for incoming Malonyl-CoA in the FA Synthase complex