Lecture 9: Fatty Acid Metabolism I Flashcards Preview

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Flashcards in Lecture 9: Fatty Acid Metabolism I Deck (38):
1

What are the functions of lipids?

-Fuel stores
-Structure components
-Signaling molecules
-Other roles (insulation, generating heat, fat digestion)

2

What is the major source of carbon for fatty acid synthesis?

Dietary carbohydrates

3

Where does Fatty Acid (FA) synthesis occur?

Primarily in liver;

also in adipose tissue

4

Fatty acid synthesis requires coordination between...

cytosolic and mitochondrial reactions

5

What is the precursor of FA synthesis?

Acetyl-CoA

6

What are the three steps in the synthesis of fatty acids?

Phase I: Cytosolic entry of Acetyl CoA

Phase II: Generation of Malonyl CoA

Phase III: Fatty acid chain formation

7

What is the rate limiting step in phase II?

Acetyl CoA Carboxylase:

Conversion of acetyl CoA (2 carbon) to Malonyl CoA (3 carbon)

8

Importance of Malonyl CoA?

REGULATOR: inhibits carnitine acyltransferase (rate limiting step in FA degradation)

9

Importance of Malonyl CoA?

REGULATOR: inhibits carnitine acyltransferase (rate limiting step in FA degradation)

-Prevents FA synthesis and degradation from occuring simultaneously

10

What occurs during phase III?

Fatty acid chain formation

11

What is required to form fatty acid chains?

Fatty Acid Synthase (FAS) complex

12

Describe the reaction that occurs in phase III

Malonyl CoA (2C) added to growing fatty acyl chain in 7 reactions to form palmitate (16:0)

13

What is Fatty Acid Synthase (FAS)?

-Large multi-enzyme complex
-2 identical dimers
-Head to tail conformation
-Each has 7 enzyme activities and an acyl carrier protein (ACP)

14

What is the major source of NADPH?

PPP (2-12)

15

How many points of regulation are there for Fatty Acid Synthesis?

3

16

What are the points of regulation for Fatty Acid Synthesis?

1. ATP citrate lyase (Phase 1)
2. Acetyl CoA Carboxylase (Phase 2)
3. Fatty acid synthase (Phase 3)

17

Regulation of ATP citrate lyase

What is it stimulated by?

Phosphorylation

18

Regulation of ATP citrate lyase

Gene expression induced by

glucose/insulin

19

Regulation of ATP citrate lyase

Induction of gene expression is counteracted by

-polyunsaturated fatty acids (PUFAs)

-leptin

20

***What is the rate limiting step of FA synthesis?

Acetyl CoA Carboxylase

21

Acetyl CoA Carboxylase

*Allosteric regulation
What activates?

Citrate

22

Acetyl CoA Carboxylase

*Allosteric regulation
What stops it?

Long chain fatty acids

23

Regulation of FAS

What increases activity?

Allosteric effect: increase activity

24

Regulation of FAS

Induction and repression at gene level:

What are examples that increase synthesis?

-Insulin
-Glucocorticoid hormones
-High carb/low fat diet

25

Regulation of FAS

Induction and repression at gene level:

What are examples that decrease synthesis?

-High fat diet
-Starvation
-High PUFA

26

What is Leptin?

16-kDa protein

-Related in direct proportion to fat mass
-Acts through leptin receptor
-Expressed in hypothalamus
-Regulates body weight

27

Synthesis of longer chain FA; Elongation

Where does elongation occur?

Smooth endoplasmic reticulum (SER) or mitochondria

28

Synthesis of longer chain FA; Elongation

By how many carbons do FA lengthen?

2 carbons at a time

29

Synthesis of longer chain FA; Elongation

What is used as the reducing power?

NADPH

30

Synthesis of longer chain FA; Elongation

SER pathway uses _______ as carbon donor

Malonyl CoA

31

Synthesis of longer chain FA; Elongation

Mitochondria uses _______ as carbon donor

Acetyl CoA

32

What introduces double bonds in FA?

Acyl CoA Desaturases

33

Desaturation:

Humans cannot form double bond beyond what carbon?

9 & 10

34

Desaturases are induced by

Insulin

35

Desaturases are suppressed by

Dietary PUFAs

36

CORRELATION BOX:

Importance of consuming essential fatty acids?

humans cannot synthesize w-3 and w-6 fatty acids, need it to make

-Arachidonic acid and Eicosapentanoic acid, Docosahexoanoic acid

37

What does Linoleic acid create?

Arachidonic acid (w6), which is a precursor for eicosanoids

38

What does Linolenic acid create?

Eicosapentanoic acid (EPA) w3 and docosahexanioic acid (DHA)