Lect 7 Lipid Degradation Flashcards Preview

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Flashcards in Lect 7 Lipid Degradation Deck (24):
1

What size FA can diffuse into Mitochondria?

Short Chain FA (SCFA)

Medium Chain FA (MCFA)

2

What size FA need to be actively Transported?

Long Chain FA (LCFA)

Very Long Chin FA (VLCFA) - Oxidized in Peroxisomes down to LCFA

3

What is the process of Phase I of FA Catabolism (Transport into Mitochondria)

How do LFCAs get into mitochondria?

What is the rate limiting enzyme located in the intermembrane space? How is it regulated?

How does it get into the mitochondria matrix for breakdown?

What enzyme in the inner membrane converts it back to CoA?

  • Cytosol: LFCAs + CoA --> Fatty Acyl CoA (via fatty acyl CoA synthetase on outer membrane) --> Crosses outer membrane
  • FA-CoA + Carnitine (CPT1/Carnitine Palmityltransferase I or Carnitine Acyltransferase) --> FA Carnitine
    • Rate Limiting Enzyme in FA Degradation
      • Inhibited by Malonyl CoA
  • FA Carnitine --> Matrix via Carnitine-Acylcarnitine Translocase (CACT) 
    • Antiporter: FA-Carnitine in - Carnitine out
  • CPT-II (inner membrane) transfers CoA to FA-Carnitine    --> FA-CoA (Matrix)

4

What are the Typical FA Features

 

Saturated

Even numbered carbon chain

16-20 carbons

5

What are the products of B-Oxidation

Acetyl CoA (TCA)

FADH2 (e- to CoQ/ubiquinone of ETC)

NADH (e- to Complex I of ETC)

6

What are the steps in Phase II (B-Oxidation in Matrix)

What enzyme is in the first step? Product?

Product of step 3?

How many times is process repeated?

  1. Oxidation: Acyl CoA Dehydrogenase (ACAD)
    • FAD --> FADH2
    • SCAD, MCAD (defects most common), LCAD, VLCAD
  2. Hydration: Enoyl acyl CoA Hydratase
  3. Oxidation: B-hydroxyl acyl CoA dehydrogenase
    • NAD+ --> NADH
  4. Thiolysis: Acyl CoA Acyltransferase (ketothiolase)
    • Acetyl CoA formed (shortens FA by 2C
  • ​Process Repeated 7 times total

7

What is the B-Oxidation Stoichiometry

Palmitate + 7 FAD + 7 NAD+ + 7 CoA + 7 H2O 8 Acetyl CoA + 7FADH2 + 7NADH + 7H+

8

What is the first product of B-Oxidation of Odd Numbered FAs

What enzyme metabolizes the odd number FA

What is the final product and where does it go?

  • Proprionyl CoA (3C)
  • Proprionyl CoA Carboxylase (Biotin + ATP) carboxylates     --> Methylmalonyl CoA (4C)
  • Methylmalonyl CoA Mutase converts to Succinyl-CoA
    • Succinyl-CoA enters TCA cycle

9

What happens during B-Oxidation of Unsaturated FAs

What enzymes are used?

  • Metabolized until unsaturation is reached
  • Reductase reduces double bond
  • Isomerase moves the disruptive bond

10

VLCFAs - Peroxisomal B-Oxidation

When does Peroxisome B-Ox shift to Mitochondria?

Energy differences?

What toxic substance is produced and how is it dealt with?

Differences to normal B-Ox?

  • Metabolized until < 20C --> Mitochondria
  • Does not produce ATP
    • e- transferred to O2
  • Produces H2O2 --> Catalase converts to H2O and O2
  • First step is catalyzed by acyl CoA oxidase (not acyl CoA Dehydrogenase)

11

What is MCAD Deficiency?

What does it lead to?

What are the consequences?

What energy source becomes only option?

  • Impairs breakdown of MCFAs
  • Leads to Secondary Carnitine Deficiency
  • C8 FA accumulates in liver, interferes w/ urea cycle and increased levels of ammonia
  • Patients depend on glucose as energy source

12

Why are Ketone Bodies Formed

Fasting/Starving Conditions = Excessive B-Ox of FAs --> Increased Acetyl CoA

13

Ketone Body Features

Water Soluble and Acidic Compounds

Produced in Liver only

Provide energy for peripheral tissues and brain

14

Primary Ketone Body Names

Acetoacetate

B-Hydroxybutyrate

Acetone

15

Ketone Formation

  • 2 Acetyl CoA --> Acetoacetyl CoA --> HMG CoA --> Acetoacetate --> B-Hydroxybutryate OR Acetone

 

16

Utilization of Acetoacetate

  • B-Hydroxybutyrate Acetoacetate --> Acetoactyl CoA    --> 2 Acetyl CoA

17

Fuel Supply: First Few Hours of Fasting

Blood glucose --> Glycogen stored in liver and muscle

18

Fuel Supply: 1 Day Fasting

TAGs stored in adipose tissue --> FFA undergo B-Ox

19

Fuel Supply: 1-2 Weeks Starvation

Brain switches to ketone bodies

20

Fuel Supply: 3 Day Fast

Ketone bodies made in liver and proteins broken down

Glycerol from TAGs and glucogenic AAs enter gluconeogenesis (Energy to brain and RBCs)

21

Fuel Supply: 2-3 Months Starvation

TAGs depleted, proteins main source

22

Physiological Ketosis

Mild to moderate increase in ketone bodies

Occurs: fasting, pregnancy, in babies, prolonged exercise, ketogenic diet

23

Pathological Ketoacidosis

Glucagon/Insulin ratio is increased --> Favoring FA breakdown

24

Diabetic Ketosis Process

_ isn't taken into cells and _ levels drop causing _ to slow down

_ are then released and _ forms causing _ to drop

  1. No glucose uptake into cells --> OAA level drops and TCA slows
  2. Free FAs released and Ketones form
  3. Blood pH drops
  4. Coma and death