402: Mobilization, B-oxidation, Ketone Bodies

White adipose

Tissue that stores fuel (as fat)

Lipid storage is…

INFINITE (as opposed to glucose storage)

TAG Storage

Lipid droplet in adipose, with non-covalent linkages

Lipolysis

Catabolism of fat producing glycerol and 3 fatty acids

Glucose vs. Fat storage

Fat stores MORE energy than glycogen

Glycerol

Gluconeogenic precursor (when energy is low)

Important lipases:

1. Adipose triglyceride lipase (ATGL) - rate-limiting

2. Hormone-sensitive lipase (HSL)

BOTH always active UNLESS insulin present

Rate-limiting and regulated enzyme of lipolysis:

Adipose triglyceride lipase (ATGL)

Regulation of adipose triglyceride lipase (ATGL)

INACTIVATED by insulin

Regulation of hormone-sensitive lipase (HSL)

INACTIVATED by insulin

What protein in blood binds free fatty acids?

Serum albumin (holds 10 at a time)

Which organs/cells DON’T use fatty acids?

Brain and erythrocytes

Beta-oxidation

Energy-generating catabolic pathway of fatty-acid breakdown 

What energy is produced by beta-oxidation?

NADH and FADH₂ (Not ATP directly) → resp. chain

Location of beta-oxidation

Mitochondria

Beta-oxidation energy requirement

ATP to activate fatty acid → fatty acyl-CoA

What molecule can be transported into mitochondria for beta-oxidation?

Fatty acyl-carnitine

Regulated step of beta-oxidation

Carnitine acyltransferase I (CAT I) - makes fatty acyl-carnitine

Carnitine acylcarnitine translocase

Transports carnitine OUT to be used by CAT-I, acylcarnitine IN

Regulation of carnitine acyltransferase (CAT-I)

Inhibited by malonyl-CoA (reciprocal regulation)

1 cycle of beta-oxidation produces…

• 1 FADH₂

• 1 NADH

• 1 Acetyl-CoA

TOTAL energy generated by beta-oxidation for PALMITATE (16-C):

• 7 NADH

• 7 FADH₂

• 8 Acetyl-CoA

(Uses 2 ATP Total)

What does beta-oxidation of UNEVEN, saturated chains produce?

Propionyl-CoA (must be converted to succinyl CoA)

Is more or less ATP generated for uneven chains?

LESS, because propionyl-CoA needs to be converted to succinyl-CoA

(10 ATP vs. 4 ATP)

Is more or less energy generated for cis-unsaturated fatty acids?

LESS, because no net gain of electrons from FADH₂

They STILL produce 1 NADH

cis-3 fatty acid….

Skips the FADH₂ generating step, so less energy is generated

cis-4 fatty acid….

Generates FADH₂ but uses NADPH, so no net gain of electrons

Regulation of beta-oxidation occurs…

DURING transport

Ketogenesis

Synthesis of ketone bodies in the liver mitochondria

Why does ketogenesis occur?

To avoid detoxification of acetyl-CoA (fasting state, low glucose)

Ketogenic enzymes

HMG-CoA synthase and HMG-CoA lyase

Ketone bodies:

1. Acetoacetate

2. beta-hydroxybutyrate

3. Acetone (discarded as waste)

Ketolysis

Breakdown of ketone bodies for fuel

Ketolytic enzyme

3-oxoacid CoA transferase

Ketogenesis ONLY occurs in the…

LIVER

Ketolysis CANNOT occur in…

The liver, it lacks 3-oxoacid CoA-transferasee