3 - Mobilization of FA and Glycerol

What hormones stimulate fatty acid release from adipose tissue?

Glucagon, epinephrine, and norepinephrine.

What pathway do these hormones activate to mobilize fatty acids?

The Gs effector system, which activates cAMP-dependent protein kinase (PKA).

What proteins are phosphorylated by PKA during fatty acid mobilization?

Perilipin and Hormone Sensitive Lipase (HSL).

What role does Perilipin play in lipid droplet access?

When dephosphorylated, it blocks access; when phosphorylated, it releases CGI-58 which activates ATGL.

What is the function of ATGL (Adipose Triacylglycerol Lipase)?

It hydrolyzes triacylglycerols to diacylglycerols and free fatty acids.

What enzymes follow ATGL in lipid breakdown?

Hormone Sensitive Lipase and Monoacylglycerol Lipase.

How are the fatty acids and glycerol transported in the blood?

Fatty acids bind to serum albumin; glycerol is water-soluble and travels freely in plasma.

Which tissues primarily metabolize glycerol?

Liver and kidney.

Why can't adipose tissue metabolize glycerol?

It lacks a glycerol transporter and glycerol kinase.

What enzyme converts glycerol to glycerol-3-phosphate?

Glycerol kinase.

What is glycerol-3-phosphate converted into?

Dihydroxyacetone phosphate (DHAP) via Glycerol-3-phosphate dehydrogenase.

What metabolic pathway does DHAP enter in the liver?

Gluconeogenesis

Where does activation of fatty acids occur?

• Short/medium-chain (≤12 C): mitochondrial matrix

• Long-chain (>12 C): cytosol

What enzyme catalyzes fatty acid activation?

Acyl-CoA synthetase.

What is the energy cost to activate a fatty acid?

2 high energy phosphate bonds (ATP → AMP + 2Pi).

What is formed during fatty acid activation?

Fatty acyl-CoA (fatty acid linked to CoA via thioester bond).

How are long-chain fatty acids transported into the mitochondrial matrix?

Via the carnitine shuttle system.

What enzymes are involved in the carnitine shuttle?

• Carnitine Acyltransferase I (outer membrane)

• Carnitine-acylcarnitine translocase

• Carnitine Acyltransferase II (inner membrane)

What is the rate-limiting step of fatty acid oxidation?

Entry of fatty acids into mitochondria via Carnitine Acyltransferase I.

What inhibits Carnitine Acyltransferase I?

Malonyl-CoA (prevents futile cycling during fatty acid synthesis).