Lecture 16

Question 1

Oxidation of Monounsaturated FA’s:

Answer 1

○ Regular β-oxidation until reach cis bond.
○ Isomerize
○ Then continue at step 2 of β-oxidation
§ skips 1st step (No FADH2 made)
○ Overall, just one fewer FADH2 made

Question 2

Oxidation of PUFA’s :

Answer 2

○ regular β-oxidation until reach cis bond.
○ Isomerize.
○ Then continue at step 2 of β oxidation.
§ skips 1st step (no FADH2 made)
○ Also step 1 of next round . . .
§ Make FADH2
○ Reduce with NADPH equivalent of losing 1 NADH.
○ Isomerize continue at step 2 of β-oxidation
§ Already did Step 1, so no FADH2 loss.
○ Overall, one fewer FADH2 and NADH made.

Question 3

Oxidation of Odd carbon Fatty Acids:

Answer 3

○ Most dietary FAs are even-numbered
§ many plants, some marine organisms produce odd-numbered FA’s
○ Final round of β-oxidation produces:
§ 1 AcCoA
§ 1 propionyl-CoA (3 carbons) —> enters TCA as succinyl-CoA
○ 2 fewer NADH made
§ requires biotin (Vit B7), cobalamin (Vit B12), and ATP

Question 4

Oxidation of Propionyl-CoA

Answer 4

1. Carboxylation:
   - uses biotin, HCO3, ATP
   - similar to pyruvate carboxylase
   2. Epimerization
   - D—>L
   3. Isomerization
   - switch carboxyl and CoA groups
   ○ Make succinyl-CoA (to TCA)
   - skips isocitrate dehydrogenase and α-KG DC
   ○ Overall, two fewer NADH made.

Question 5

Regulation of β-Oxidation:

Answer 5

○ 2 options for fatty acyl-CoA
- fatty acid synthesis
- fatty acid degradation (β-oxidation)
○ β-oxidation regulatory processes:
- Rate limiting process: acyl-CoA transport into mitochondria
○ Malonyl-CoA inhibits carnitine acyl transferase I (CAT I)
- High AMP activates AMPK (AMP kinase)
○ Phosphorylation of acetyl-CoA carboxylase to stop malonyl-CoA synthesis
- High NADH/NAD+ ratio inhibits β-hydroxyacyl-CoA dehydrogenase
- High acetyl-CoA inhibits thiolase

Question 6

Plant β-Oxidation general process:

Answer 6

○ Acetyl-CoA-----> glucose
			- involves the Glyoxysome
○ Essentially, convert TAGs to glucose
○ Germinating seeds: growth
			- need fuel for energy and biosynthesis.

Question 7

Plant β-Oxidation

Answer 7

○ Peroxisomes/glyoxysomes:

		1. Prefer very long chain fatty acids
		2. e- in first step goes directly to O2, not ETC
			- FADH2 passes e- to O2 ---> H2O2
		3. NADH exported for reoxidation 
		4. Acetyl-CoA made is used for biosynthesis, rather than the TCA cycle.

Question 8

Glyoxylate Cycle: Overview

Answer 8

○ Found in plants (and some microorganisms)
○ Net production of 2 acetyl-CoA —-> oxaloacetate
§ allows net conversion of acetyl-CoA glucose
○ Compartmentalized in glyoxysome
§ part of TCA cycle
§ Bypasses decarboxylation with two different enzymes.
- isocitrate lyase.
- Malate synthase.

Question 9

Ketone bodies:

Answer 9

○ Another fuel source from fats
○ Made in liver mitochondria
○ conditions leading to ketone body information:
§ high fat (lipid) intake/low sugar (carb) intake
§ starvation
§ uncontrolled diabetes

Question 10

Liver: source of ketone bodies:

Answer 10

○ Starvation, untreated diabetes:
§ body low on fuel
§ promote gluconeogenesis
§ deplete of oxaloacetate
○ For acetyl-CoA to go into TCA cycle, need oxaloacetate:
§ If OAA depleted, acetyl-CoA—> ketone bodies instead of TCA cycle.
§ Frees Coenzyme A (CoA) for continued β-oxidation
○ Ketone bodies released into bloodstream
○ Other organs use ketone bodies as fuels
§ heart, brain, muscle.

Question 11

Ketone Body Formation:

Answer 11

1. Join 2 acetyl-CoA (4C)
   - reverse thiolase
   - CoA released for more β-ox
   2. Add a third AcCoA (6C)
   - HMG-CoA synthase
   - CoA released for more β-ox
   3. Remove 1 AcCoA (4C)
   - HMG-CoA lyase
   - why remove? Because product has no Coenzyme A
   - recover 2 CoA for β-Ox
   4. Form other two ketone bodies from acetoacetate:
   - acetone & D-β-hydroxybutyrate (DBH)

Question 12

Use of ketone bodies as fuel:

Answer 12

○ ketone bodies from bloodstream goes to needed organs.
○ Re-convert ketone bodies to acetyl-CoA
○ Acetyl-CoA now goes through TCA cycle for energy.

Question 13

Ketone Bodies: Ketosis

Answer 13

○ High levels of acetoacetate and β-hydroxybutyrate can cause the blood pH to drop dangerously low.
- Bicarbonate buffer in blood overwhelmed.
- Acidosis, or ketoacidosis
○ Body excretes excess H+ in urine (along with Na+, K+, and H2O
- can cause severe dehydration
○ excess thirst is classes symptom of diabetes.
- can lead to diabetic coma.