Fatty Acid Degradation

Triacylglycerol (TAG)

Fatty acid storage structure

Fatty acids linked to glycerol with Ester linkages

What are the three steps for fatty acid degradation?

1. TAG degradation

2. Activation and transport of fatty acids to mitochondria

3. Fatty acid degradation to acetyl CoA

What hormone(s) stimulate fatty acid degradation?

Epinephrine

Glucagon

What is perilipin and how is it activated?

Rearranges lipid droplets

PKA activation phosphorylates and activates

Adipocyte TAG lipase

Removes fatty acid from TAG to produce DAG

Hormone sensitive lipase

Removes fatty acid from DAG to produce MAG

Depends on PKA activity (and thus hormones)

MAG lipase

Removes fatty acid from MAG to produce glycerol

Albumin

Binds insoluble fatty acids in the blood to deliver them to tissues in need

When TAG is completely degraded, where does the remaining glycerol go?

To liver for glucose metabolism (glycolysis or gluconeogenesis)

Pyrophosphate

2 Pi groups

How is acyl adenylate formed?

Fatty acids react with ATP, releasing a pyrophosphate

How is acyl CoA formed?

Sulfhydryl group on CoA attacks acyl adenylate to form acyl CoA and AMP

IRREVERSIBLE

pyrophosphatase

Breaks pyrophosphate into orthophosphate

Carnitine

transfers fatty acids across inner mitochondrial membrane

Carnitine acyltransferase I

Transfers fatty acid from CoA to carnitine

Translocase

Transports acyl carnitine into mitochondrial matrix

Carnitine acyltransferase II

Transfers fatty acid from carnitine to CoA

Enoyl CoA hydratase

Hydrates trans-delta2-enoyl CoA to produce L-3-hydroxyacyl CoA

L-3-hydroxyacyl CoA dehydrogenase

Oxidizes L-3-hydroxyacyl CoA to form 3-ketoacyl CoA and NADH

Beta-ketothiolase

Cleaves 3-ketoacyl CoA to form acetyl CoA and fatty acid - 2C

Beta oxidation

Process for fatty acid degradation

How much ATP is 1 acetyl CoA worth?

10 ATP

How much ATP is 1 NADH worth?

2.5 ATP

How much ATP is 1 FADH2 worth?

1.5 ATP

How do you calculate the number of Beta-oxidation rounds?

(#C/2) - 1

Degradation steps for saturated even chain fatty acids

Beta oxidation (complete)

Degradation steps for unsaturated odd #C 2xbond fatty acids

Beta oxidation (to cis-3-enoyl CoA)

3-enoyl-CoA isomerase converts cis-3-enoyl CoA to trans-2-enoyl CoA

Beta oxidation (to end)

Degradation steps for unsaturated even #C 2xbond fatty acids

Beta oxidation (to 2,4-dienoyl CoA)

2,4-dienoyl CoA reductase converts 2,4-dienoyl CoA to trans-3-enoyl CoA

3-enoyl-CoA isomerase converts cis-3-enoyl CoA to trans-2-enoyl CoA

Beta oxidation (to end)

Degradation steps for odd chain (saturated/unsaturated) fatty acids

Beta oxidation forms propionyl CoA

Propionyl CoA carboxylase

Biotin enzyme

Adds C to propionyl CoA to form methylmalonyl CoA

Methylmalonyl CoA mutase

Converts methylmalonyl CoA to succinyl CoA