Lecture 10: Fatty Acid Metabolism II Flashcards Preview

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Flashcards in Lecture 10: Fatty Acid Metabolism II Deck (42):
1

Fatty Acid Oxidation: Global Overview

Phase I: Where does this occur? What occurs?

Cytosol: Fatty acid activation

2

Fatty Acid Oxidation: Global Overview

Phase II: where does it occur? What occurs?

Mitochondrial matrix: Beta oxidation

3

Fatty Acid Oxidation: Global Overview

Phase I: What occurs?

Transport of FA into mitochondria

4

Fatty Acid Oxidation: Global Overview

Phase I: What can diffuse into mitochondria?

-Short chain Fatty acids (SCFAs)
-Medium chain fatty acids (MCFAs)

5

Fatty Acid Oxidation: Global Overview

Phase I: What needs to be actively transported?

-Long chain fatty acids (LCFAs)
-Very long chain fatty acids (VLCFAs)

6

Function of Acyl Carnitine Translocase?

***

7

What occurs during phase II of fatty acid oxidation?

Beta-oxidation

8

What composes typical fatty acids?

-Saturated
-Even numbered carbon chain
-16-20 carbons

9

Phase II- Beta oxidation

The four main steps generate...

-Acetyl CoA (enters TCA cycle)
-FADH2 (delivers electrons to CoQ/ubiquinone of ETC)
-NADH (delivers electrons to Complex I of ETC)

10

Phase II- Beta Oxidation

What are the four steps?

1. Oxidation
2. Hydration
3. Oxidation
4. Thiolysis

11

Major enzyme to remember for phase II?

Acyl CoA Dehydrogenase (ACAD)

12

Describe the first step of Beta Oxidation:

Acyl CoA dehydrogenase (ACAD): oxidizes the beta carbon to produce FADH2 and trans-enoyl-CoA. FADH2 enters CoQ of ETC to generate 2 ATPs

13

Inherited defects in ______ are most common with Acyl CoA Dehydrogenase (ACAD) deficiency

MCAD

14

Net ATP created from FA oxidation?

106 ATP

15

What are the 4 enzymes in the carnitine shuttle?

1. Fatty acyl CoA Synthetase
2. Carnitine palmitoyltransferase I (CPT1)
3. Carnitine acylcarnitine translocase (CACT)
4. Carnitine palmitoyltransferase II (CPT II)

16

What is the rate limiting step in FA degradation?

Carnitine palmitoyltransferase I (CPT1)

17

What are the four steps of beta oxidation?

OHOT!!!

1. Oxidation
2. Hydration
3. Oxidation
4. Thiolysis

18

Carnitine Shuttle:

1. Describe Fatty Acyl CoA synthetase

-Located on the outer mito-membrane
-Adds a Co-A group to fatty acids by using ATP
-Forms thioester bond b/w FAs and CoA to form FAcoA

19

Carnitine Shuttle:

2. Describe Carnitine Palmitoyltransferase-I (CPT 1) aka carnitine acyltransferase

-Located in intermembrane space
-Transforms Fatty acyl CoA into FATTY ACID CARNITINE

***RATE LIMITING STEP

Inhibited by Malonyl CoA

20

Carnitine Shuttle

3. Describe Carnitine-acylcarnitine translocase (CACT)

-Antiporter: Carnitine (out) FA carnitine (in)

21

Carnitine Shuttle

4. Describe Carnitine palmitoyltransferase II (CPT-II)

-Located in inner mitochondrial membrane
-Transforms Fatty acyl-carnitine into fatty acyl coA

RESULT: Fatty acyl carnitine now in mt. matrix

22

What is phase II of fatty acid degradation?

Beta-oxidation

23

Beta-oxidation can completely break down...

Typical fatty acids:

Saturated, even numbered carbon chain, 16-20 carbons

24

What do the four main steps of beta oxidation create?

-Acetyl CoA (enters TCA cycle)
-FADH2 (delivers e- to CoQ/ubiquinone of ETC)
-NADH (delivers electrons to Complex I of ETC)

25

What are the four steps of Beta-oxidation?

1. Oxidation *ACAD
2. Hydration
3. Oxidation
4. Thiolysis

26

In phase II of FA degradation, what occurs with (Atypical FAs, Odd # Cs)?

1. Metabolized until Propionyl CoA remains (3 carbons)
2. Propionyl CoA Carboxylase uses ATP to carboxylate to Methylmalonyl CoA
3. SUCCINYL-COA ENTERS TCA

27

In phase II of FA degradation, what occurs with (Atypical FAs, VLCFAs *more than 20 Cs)?

Metabolized in peroxisomes

28

In phase II of FA degredation, what occurs with (Atypical FAs, Unsaturated FA)?

NEED NOVEL ENZYMES:
-Enoyl CoA reductase: reduces double bond
-Enoyl CoA isomerase: moves the disruptive bond

29

KEY DIFFERENCE for VLCFAs and peroxisomal Beta oxidation

First step is catalyzed by acyl-CoA oxidase

30

CORRELATION BOX: MCAD Deficiency

Describe

-Disorder of FA-beta-oxidation that IMPAIRS BREAKDOWN OF MCFAs
-Leads to secondary carnitine deficiency
-C8 FA accumulates in liver, poisonous, interferes with urea cycle, elevated levels of ammonia
-Pts depend on glucose as energy source

31

What occurs during starvation?

Excessive Beta-oxidation of FAs --> increased acetyl-CoA

32

What are ketone bodies?

Water-soluble and acidic compounds

-Acetoacetate, Beta-hydroxybutyrate, Acetone

33

Where are ketone bodies produced?

LIVER ONLY

34

What is the function of ketone bodies?

Provide energy for peripheral tissues during fasting and starvation

35

CORRELATION BOX: Fuel Supplies during Fasting and Starvation

First few hours of fasting?

Blood glucose, then glycogen in liver and muslce, then gluconeogenesis

36

CORRELATION BOX: Fuel Supplies during Fasting and Starvation

After 1 day of fasting?

TAGs stored in adipose tissue

37

CORRELATION BOX: Fuel Supplies during Fasting and Starvation

After 3 days of fasting?

Ketone bodies made in liver and proteins in muscle broken down

38

CORRELATION BOX: Fuel Supplies during Fasting and Starvation

After 1-2 weeks starvation?

Brain switches to ketone bodies as major energy source

39

CORRELATION BOX: Fuel Supplies during Fasting and Starvation

After 2-3 months of starvation?

TAGs depleted, proteins main source

40

CORRELATION BOX: Ketoacidosis during Starvation and Diabetes

What is physiological ketosis?

Mild to moderate increase in ketone bodies

41

CORRELATION BOX: Ketoacidosis during Starvation and Diabetes

What is pathological ketoacidosis?

Occurs when glucagon/insulin ratio is increased, favoring FA breakdown

42

Carnitine deficiency is common in...

strict vegetarians