Unit 13: Lipids & Fatty Acid Catabolism

What carbon is alpha, beta, & omega?

• Alpha - 2

• Beta - 3

• Omega - last

What does it mean for fatty acid to be saturated?

No double bonds

What does it mean for a fatty acid to be unsaturated?

At least 1 double bond

What are unsaturated fatty acids referred to?

• Monounsaturated (1 double bond)

• Polyunsaturated (more than 1 double bonds)

What are aspects of polyunsaturated fatty acids?

• Can be varying lengths

• Most naturally occurring has even number of carbons

• Double bonds are designed by delta & usually cis configuration

• Double bonds normally occur in same positions & are 3 carbon atoms apart & rarely conjugated

Are fatty acids with an odd number of carbons common or uncommon?

Uncommon

What happens first with fatty acid oxidation?

• Release of fatty acids from adipose tissue

  • Glucagon role: mobilizes fuel sources & stimulates kinase

  • Key enzyme: lipase

What can be used for energy if necessary in fatty acid oxidation?

Glycerol

What is the ATP cost in fatty acid oxidation?

• 2 ATP/fatty acid

• Glycerol → glycerol 3-P → dihydroxyacetone phosphate

• Enzymes: kinase & dehydrogenase

Where does activation of fatty acids occur?

Cytosol of cell

What is used & produced in activation of fatty acids?

• Used: ATP (2 high energy bonds)

• Produced: acetyl CoA, AMP (no high energy bonds), PPi (pyrophosphate)

What does the pyrophosphate do in fatty acid oxidation?

Rapidly hydrolyzed, releases energy, & drives reaction forward

What happens after activation of fatty acid?

Transfer of fatty acids into mitochondria

What do the fatty acids need since inner membrane is impermeable to H₂O soluble molecules?

Transporter

What is the carrier for fatty acids into mitochondria?

Carnitine

• Hydroxyl group is responsible for “carrying” acyl group

What is the transporter for the fatty acids into mitochondria?

Translocase

What does fatty acids oxidation occur in?

Repeating “rounds”

How many steps is fatty acid oxidation?

4 steps

What does fatty acid oxidation (beta-oxidation) require with enzymes?

2 dehydrogenase enzymes

• Produce NADH or FADH₂

What does fatty acid oxidation do to the fatty acid?

Shortens it by 2 carbons

What are steps 1-3 of fatty acid oxidation similar to of CAC?

Steps 6-8 of CAC

What are the 4 steps of fatty acid oxidation?

1. Catalyzed by acyl-CoA dehydrogenase

• Hydrocarbon, FAD added to form double bond

2. Catalyzed by enoyl-CoA hydratase

• Adds H₂O across bond

3. Catalyzed by beta-hydroxyacyl-CoA dehydrogenase

• C-OH is oxidized to C=O with NAD+

4. Catalyzed by acyl-CoA transferase (thiolase)

• Cuts 2 carbons off of fatty acid → acetyl CoA

How to calculate how many rounds are required?

(x/2 - 1)

What is different about final round of fatty acid oxidation?

4 carbon fatty acid is cut into 2 acetyl CoA

What happens when there is a double bond at an odd numbered carbon atom?

In step 1, use isomerase instead of dehydrogenase

• No ox/red takes place in step 1 & no FADH₂ is made

• Cost of 1.5 ATP

What happens when there is a double bond at an even numbered carbon atom?

• All 4 steps are used

• 2 additional steps take place between steps 2 & 3

  • Reductase enzyme & isomerase

• All resources are formed

What happens when there is high blood glucose?

• Insulin is released (favors storage)

• Releases phosphatase

• Acetyl CoA → fatty acids (storage)

What happens with low blood glucose?

• Glucagon increased

• Kinase released

• Favors mobilization

What does increased malonyl CoA do?

Inhibits the shuttle

What does Acetyl CoA → malonyl CoA require?

• Carboxylase

• CO₂0

• Biotin

What are the 2 enzymes within the beta-oxidation pathway regulated by?

Metabolites (feedback control)

• beta-hydroxyacyl-CoA dehydrogenase is inhibited when NADH/NAD+ ratio is high

• Thiolase is inhibited when high acetyl CoA (product feedback)

When can the acetyl CoA formed in fatty acid oxidation enter CAC only if?

Oxaloacetate is present

What increases with decreased oxaloacetate availability?

Higher formation of ketone bodies

What is the diversion of acetyl CoA to without oxaloacetate?

Acetoacetate & D-3-hydroxybutyrate (Both ketone bodies & acidic)

• Cause acidosis in higher concentrations

What are the pathological conditions for ketone bodies to form?

• Fasting

• Starvation

• Uncontrolled diabetes

What is the normal function with acetoacetate & 3-hydroxybutyrate?

• Transported in blood to extrahepatic tissues where used for energy

• Some cells use acetoacetate in preference to glucose

What can acetoacetate be viewed as?

Water soluble, transportable form of acetyl COA

• Also regulatory role: high [acetoacetate] decreases beta-oxidation

How can acetoacetate → acetyl CoA?

With CAC intermediate & thiolase