Fatty Acid Degradation and Synthesis

During hormone-stimulated lipolysis in adipocytes, what is the role of protein kinase A?

It phosphorylates perilipin and hormone-sensitive lipase to promote fat breakdown

Sequence representing the four recurring reactions of beta oxidation

Oxidation → hydration → oxidation → thiolysis (O HOT)

What is the first step of fatty acid degradation?

Breakdown to fatty acids and glycerol by lipases (stimulated by glucagon and epinephrine, down-regulated by insulin)

What is the second step of fatty acid degradation?

Activation by attachment of CoA, transport across the inner mitochondrial membrane as acyl carnitine, then reattachment of CoA

What is the third step of fatty acid degradation?

Degradation to acetyl CoA by beta-oxidation (OHOT)

Degradation of unsaturated and odd-chain fatty acids requires additional steps, which are?

• Reductases and isomerases

• Conversion of propionyl CoA to succinyl CoA

What is the first stage of fatty acid synthesis, what is the location, and which enzymes are involved?

Transport

• Location: mitochondria → cytosol

• Enzyme: ATP-citrate lyase

• Citrate carries acetyl units out of the mitochondria to be broken back down to acetyl CoA in the cytosol

What is the second stage of fatty acid synthesis, what is the location, and which enzymes are involved?

Activation

• Location: cytosol

• Enzyme: Acetyl-CoA Carboxylase (ACC)

• Acetyl CoA + ATP → Malonyl CoA

What is the third stage of fatty acid synthesis, what is the location, and which enzymes are involved?

Elongation

• Location: cytoplasm

• Enzyme: Fatty Acid Synthase (FAS) complex

• Acetyl CoA + 7 malonyl CoA + 14 NADPH + 20H+ → palmitate + 7CO2 + 14 NADP+ + 8 CoA + 6H2O

How are fatty acids longer than C16 made?

They are made by elongating palmitate (16:0) in the smooth ER, adding 2 carbons at a time (malonyl CoA)

How are unsaturated fats made?

Occurs mainly in the smooth ER, where desaturase enzymes introduce cis double bonds

• requires O2 and reducing equivalents

Which enzyme is the key regulator of fatty acid metabolism?

Acetyl-CoA Carboxylase (ACC)

• converts acetyl CoA into malonyl CoA

• insulin activates ACC, initiating fatty acid synthesis

• glucagon/epinephrine inhibits ACC

Reciprocal regulation of fatty acid degradation and biosynthesis

Insulin activates synthesis and inhibits degradation

Glucagon and epinephrines inhibit synthesis and activate degradation