Lecture 28 - beta oxidation of fatty acids 2

Question 1

What is the overall reaction for beta oxidation

Answer 1

Cn-ACYL-CoA + FAD + NAD+ + H2O + CoA

Cn-2-ACYL-CoA + FADH2 + NADH + H+ + ACETYL-CoA

Question 2

What happens to the acetyl-CoA produced?

Answer 2

Enters the TCA cycle
OR
Made into ketone bodies

Most goes into the TCA cycle unless there is a shortage of carbohydrate/a lot of fatty acid metabolism

Question 3

What is the Overall reaction for the TCA cycle

Answer 3

Acetyl-CoA + 3 NAD+ + FAD + GDP + Pi + 2H2O —>

2 CO2 + 3 NADH + 3H+ + FADH2 + GTP + CoA

Question 4

What is the total production from the 8 acetyl CoAs from palmitate

Answer 4

8 x 3 = 24 NADH + H+
8 x 1 = 8 FADH2
8 x 1 = 8 GTP

Question 5

What is the rough efficiency of beta oxidation of FA

Answer 5

Energy captured is 129 times the Free energy of hydrolysis of one phosphate from ATP

129 x -31kJ/mole = -3999kJ/mole

Standard Free energy of oxidation of palmitate
-9790kJ/mole

Proportion of energy captured = -3999/-9790 = ~40%

Question 6

What is the yield per carbon oxidised to CO2

Answer 6

No. of ATP = 129 = ~8.2
No. of carbons 16

Equivalent figure for glucose is ~6.3

Question 7

When are ketone bodies not always present in large enough quantities

Answer 7

Fasted periods

Oxaloacetate is needed for entry of acetyl-CoA into the TCA cycle

Question 8

Where are ketone bodies mainly produced

Answer 8

Liver

Oxaloacetate being used for glucose synthesis (gluconeogenesis)[so not available to allow acetyl-CoA into TCA cycle]

Major site of key enzymes of ketone body synthesis

Question 9

Why are ketone bodies considered “energy rich”

Answer 9

Water soluble – so easily transported in the blood

Easily broken down

Question 10

What are the major users of ketone bodies

Answer 10

Heart and renal cortex

Question 11

Ketone body formation in mitochondria mechanism

Answer 11

2 Acetyl-CoA <–Thiolase–> Acetoacetyl-CoA + CoA-SH

Acetoacetyl-CoA –HMG-CoA Synthase–> Beta-hydroxy-beta-methylglutaryl-CoA (HMG-CoA)

Side reaction in second step - Acetyl-CoA + H2O –> CoA-SH

HMG-CoA –HMG-CoA lyase–> Acetoacetate + Acetyl-CoA

THEN EITHER

Acetoacetate –Acetoacetate decarboxylase–> Acetone + CO2

OR

Acetoacetate <–D-beta-hydroxybutyrate dehydrogenase–> D-beta-hydroxybutyrate

(NADH+H+ —> NAD in second stage of this)

Question 12

Ketone body utilisation mechanism

Answer 12

D-beta-hydroxybutyrate converted back to acetoacetate by D-beta-hydroxybutyrate dehydrogenase

acetoacetate converted to acetoacetyl-CoA by betaketoacyl-CoA transferase

Synthesising Succinate from Succinyl-CoA

Acetoacetyl-CoA + CoA-SH –Thiolase–> 2 Acetyl-CoA