Midterm II: Fatty Acid Oxidation (Ben) Flashcards Preview

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1

What are longer free fatty acids bound to for transport in the blood?

How many FAs per unit of this transport molecule?

Albumin

- 10 FAs per albumin monomer

2

How does transport of shorter chain fatty acids differ from longer?

SCFAs are more water-soluble and exist in unionized or anion forms

3

What is the first step of catabolism of a free fatty acid?

What is special about this step energetically?

Fatty Acid Activation

- with CoA and ATP via acyl-CoA synthetase

- it is the ONLY step of FA oxidation which uses ATP

4

What is the enzyme which "activates" fatty acids for oxidation and where is it found (4 locations)?

Acyl-CoA Synthetase

Found:

  1. in the ER
  2. in peroxisomes
  3. in mitochondria
  4. on mitochondrial outer membrane

5

What is the overal reaction of FFA activation?

Include the enzyme.

FFA + CoA + ATP

---- acyl-CoA synthetase ---->

acyl-CoA + PPi + AMP

6

What happens to the PPi formed from cleaved ATP during fatty acid activation and why?

it is hydrolyzed by inorganic pyrophosphatase

- to ensure that the reaction is carried out fully and is irreversible in vivo

7

What is the site of fatty acid activation?

the outer mitochondrial membrane

(where acyl-CoA synthetase is found)

8

What happens to acyl-CoA in the intermembrane space?

(before it can enter the mitochondrial matrix)

Carnitine Palmitoyltransferase-I

(or Carnitine Acyltransferase-I)

- catalyzes transfer of acyl group from CoA to carnitine to form acylcarnitine

9

How does acylcarnitine penetrate the inner mitochondrial membrane?

via Carnitine-Acylcarnitine Translocase

- exchanges carnitine for acylcarnitine across the membrane

10

What happens to acylcarnitine once it is inside the mitochondrial matrix?

Start with the enzyme, then describe the process.

Carnitine Palmitoyltransferase-II

(or Carnitine Acyltransferase-II)

- transfers acyl group to CoA reforming Acyl-CoA and liberating carnitine

11

Where is Carnitine Palmitoyltransferase-I located?

across the outer mitochondrial membrane

12

Where is Carnitine-AcylCarnitine Translocase located?

across the inner mitochondrial membrane

13

Where is Carnitine Palmitoyltransferase-II located?

on the inside of the inner mitochondrial membrane

14

Why is β-oxidation called β-oxidation?

because it is a cycle of successive cleavages of Acyl-CoA molecules at...

the C-C bond between the α(2) and β(3) carbons

(2nd and 3rd Cs from the -COOH end)

15

What is the collective name for the enzymes which perform β-oxidation?

And where are they found?

Fatty Acid Oxidase

- found in the mitochondrial matrix and inner mitochondrial membrane 

(adjacent to to the respiratory chain)

16

Energetically, what are the important products (3) of β-oxidation?

How are they used?

  1. FADH2 - oxidative phosphorylation > ATP
  2. NADH - oxidative phosphorylation > ATP
  3. Acetyl-CoA - citric acid cycle > ATP + NADH + FADH2

17

What is the first step of β-oxidation?

Substrates/reactants?

Enzyme?

Products?

Removal of one hydrogen each from α and β carbons...

Reactants: Acyl-CoA + FAD

Enzyme: Acyl-CoA Dehydrogenase

Products: Δ2-trans-Enoyl-CoA + FADH2

18

What is the 2nd step of β-oxidation?

Substrates/reactants?

Enzyme?

Products?

 

Water is added to saturate the double bond...

Reactants: Δ2-trans-Enoyl-CoA + H2O

Enzyme: Δ2-Enoyl-CoA Hydratase

Products: L-β-Hydroxy-acyl-CoA

19

What is the 3rd step of β-oxidation?

Substrates/reactants?

Enzyme?

Products?

What is special about the enzyme?

 

Further dehydrogenation of the 3-carbon...

Reactants: L-β-Hydroxyacyl-CoA + NAD+

Enzyme: β-Hydroxacyl-CoA Dehydrogenase

Product: β-Ketoacyl-CoA + NADH + H+

The enzyme is stereospecific for the L-isomer.

20

What is the 4th step of β-oxidation?

Substrates/reactants?

Enzyme (2 names)?

Products?

How is one of the end products different from what entered β-oxidation?

 

Cleavage at the 2,3 position...

Reactants: β-Ketoacyl-CoA + CoA-SH

Enzyme: Thiolase (or Acyl-CoA Acetyltransferase)

Products: Acetyl-CoA + Acyl-CoA 

Acyl-CoA product here is 2 carbons shorter than acyl-CoA which entered the cycle.

21

How does a fatty acid chain's length affect how it is transported into the mitochondria?

  • > 12C - with carnitine
  • < 12 C - without carnitine, activated in mitoch.

22

Which β-oxidation enzyme has 3 different isoforms?

What for?

What are they?

Which one is frequently deficient?

Acyl-CoA Dehydrogenase (the 1st step)

- for different lengths of fatty acids

  • LCFAs (C 12-18)
  • MCFAs (C 4-14) - frequently deficient (MCAD)
  • SCFAs (C 4-8)

23

How many ATP are ultimately formed per NADH produced in β-oxidation?

Per FADH2?

NADH - 2.5 ATP

FADH2 - 1.5 ATP

24

Where are > 12 C FAs oxidized?

And < 12 C?

> 12 C - on the inner mitochondrial membrane 

< 12 C - via soluble enzymes in the mitochondrial matrix

25

What is special about the last 3 enzymes of β-oxidation?

And what are the 3 enzymes?

they are a tightly associated trifunctional protein

  • enoyl-CoA hydratase
  • β-hydroxyacyl-CoA dehydrogenase
  • thiolase

26

What results from the breakdown of an odd-chain fatty acid?

Where can this go and what can it become?

The remaining 3C residue is...

Propionyl-CoA

...which is converted to succinyl-CoA and enters the citric acid cycle

- in this way, it is the only glucogenic part of any fatty acid

27

How are very long chain fatty acids oxidized?

What products result from this?

VLCFAs (C20/22) are oxidized in peroxisomes

- forming acetyl-CoA and H2O2

- BUT this β-oxidation sequence ends at Octanoyl-CoA and is continued in mitochondria

28

What is the first step of glycerol conversion to a glycolysis intermediate in the liver?

Enzyme + product + special reactant

Phosphorylation of glycerol...

Reactants: Glycerol + ATP

Enzyme: Glycerol Kinase

Products: Glycerol-3-phosphate + ADP

29

What is the 2nd step of glycerol conversion to a glycolysis intermediate in the liver?

(Enzyme + products + special reactants)

Dehydrogenation of G-3-P...

Reactants: G-3-P + NAD+

Enzyme: Glycerol-3-phosphate Dehydrogenase

Products: DHAP + NADH + H+

30

What two hormones induce increased fatty acid oxidation in the fasting/low-glucose state?

How?

Epinephrine/Adrenaline + Glucagon

Induce increased oxidation via:

  • Phosphorylation/Inhibition of Perilipin (lipid droplet "protecting" protein)
  • Activation of Hormone-sensitive Lipase