Beta oxidation of fatty acids

Biochemistry Y1S2

What is the beta oxidation pathway?

The process by which fatty acids are broken down to release energy

Which carbon is the beta carbon?

The second carbon atom adjacent to the carboxyl group in a fatty acid (third including the carboxyl group)

How are fatty acids broken down?

by removal of two-carbon groups

Which bond is broken?

The bond between the alpha and beta carbons is broken during beta oxidation.

What are the products?

benzoate and a 2 carbon unit

Activation step

formation of acyl-CoA from fatty acid acyl groups (by using ATP and CoA).

RCOO- + CoA + ATP → acyl-CoA + AMP + PPi

Transport step

involves the transport of fatty acids into the mitochondria via the carnitine shuttle

Acyl CoA + carnitine → Acyl carnitine + HS-CoA

(catalysed by carnitine acyltransferase I)

Where does the acyl group attach on carnitine?

in place of hydroxyl, releasing CoA

Step 1 of oxidation stage

Dehydrogenation

Palmitoyl-CoA → trans-delta2-enoyl-CoA

Produces FADH2 and catalysed by acyl-CoA dehydrogenase.

Step 2 of oxidation stage

Hydration

trans-delta2-enoyl-CoA → L-beta-hydroxyacyl-CoA
Involves the addition of water, catalysed by enoyl-CoA hydratase

Step 3 of oxidation stage

Dehydrogenation

L-beta-hydroxyacyl-CoA → beta-ketoacyl-CoA
Produces NADH and is catalysed by beta-hydroxyacyl-CoA dehydrogenase.

Step 4 of oxidation stage

Thiolytic cleavage

beta-ketoacyl-CoA → acyl-CoA + acetyl-CoA

Involves the addition of CoA-SH and is catalysed by acyl-CoA acetyltransferase (thiolase).

Overall reaction for beta oxidation

C_n-acyl-CoA + FAD + NAD⁺ + H₂O + CoA → acetyl-CoA + FADH₂ + NADH + H⁺ + C_n-2-acyl-CoA

Overall reaction for TCA cycle

Acetyl-CoA + 3NAD⁺ + FAD + GDP + Pi +2H₂O → 2CO₂ + 3NADH + FADH₂ + GTP + CoA + 3H⁺

1st step of ketone body formation

2 acetyl-CoA → acetoacetyl-CoA, catalysed by thiolase

2nd step of ketone body formation

acetoacetyl-CoA + acetyl-CoA → HMG-CoA, catalysed by HMG-CoA synthase

HMG-CoA is an important intermediate eg in production of cholesterol. Too much of it can lead to overproduction of cholesterol

3rd step of ketone body formation

HMG-CoA → acetoacetate (1st component of ketone bodies produced) + acetyl-CoA, catalysed by HMG-CoA lyase.

4th step of ketone body formation

acetoacetate → D-beta-hydroxybutyrate, catalysed by D-beta-hydroxybutyrate dehydrogenase. Uses NADH, converts to NAD+

Utilisation of ketone bodies - what happens once inside cells?

D-beta-hydroxybutyrate → acetoacetate

NAD+ → NADH + H+

catalysed by D-beta-hydroxybutyrate dehydrogenase.

2nd step of ketone body utilisation

acetoacetate → acetoacetyl-CoA

requires CoA in the form of succinyl-CoA (succinate is a product)

catalysed by beta-ketoacyl-CoA transferase

final step of ketone body utilisation

acetoacetyl-CoA → 2 acetyl-CoA

requires CoA in the form of CoA-SH

catalysed by thiolase.

acetyl-CoA can then enter the TCA cycle which is not limited by the amount of oxaloacetate.

What organs or tissues prefer to use ketone bodies such as acetoacetate as a sourceof fuel instead of glucose?

heart and renal cortex

Which of the following is not a ketone body:

acetoacetate

beta-hydroxybutyrate

acetone

acetaldehyde

acetaldehyde

Theoretically what is the net gain in ATP from complete oxidation of palmitate?

129 ATP

Overall equation for fatty acid oxidation (1 cycle)

C_n-acyl CoA + FAD + NAD⁺ + H₂O + CoA → C_n-2-acyl CoA + FADH₂ + NADH + acetyl CoA + H⁺

How many ATP does oxidation of acetyl CoA by the citric acid cycle produce?

10