Metabolism II: Lipid Metabolism Flashcards

1
Q

Two essential features of fatty acids

A
  • long hydrocarbon chain

- carboxylic acid group

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2
Q

What is the most common chain length of the long hydrocarbon chain in FAs?

A

12-24 carbons

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3
Q

Long hydrocarbon chain of FA features

A
  • chain typically linear
  • usually contains even number of carbons
  • 4 - 30 Carbons
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4
Q

The FAs that occur naturally arise primarily through variation of what?

A

chain length

degree of saturation

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5
Q

What is one way FAs can be classified

A

based on number of double bonds

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6
Q

What type of FA has 0 double bonds?

A

saturated

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7
Q

What type of FA has one double bond

A

monounsaturated

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8
Q

What type of FA has 2 or more double bond?

A

polyunsaturated

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9
Q

What is an example of a saturated FA?

A

Stearic acid

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10
Q

What is an example of a monounsaturated FA?

A

Oleic acid

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11
Q

What is an example of a polyunsaturated FA?

A

Linoleum acid

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12
Q

What is the most commonly synthesized FA?

A

palmitic acid

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13
Q

What type of FAs cannot be synthesized in the body?

A

essential

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14
Q

w-6 and w-3 FAs are examples of what kind of FA?

A

essential

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15
Q

w-6 FA

A

Linoleum acid

18:2

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16
Q

w-3 FA

A

linolenic acid

18:3

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17
Q

What are linoleum acid and linolenic acid mainly produced by?

A

plants

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18
Q

Sources of FAs

A
  • diet
  • de novo lipogenesis
  • mobilization from adipose tissue
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19
Q

Where are FAs stored as in adipocytes?

A

triacylglycerol

- constantly hydrolyzed and resynthesized

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20
Q

Adipocytes

A

metabolically very active

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21
Q

What is R1 of triacylglycerol often?

A

palmitate

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22
Q

What is R2 of triacylglycerol often?

A

oleate

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23
Q

What is R3 of triacylglycerol often?

A

oleate or a polyunsaturated fatty acyl group

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24
Q

What type of FA is released from the adipocytes?

A

nonesterfied FA

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25
Q

The release of nonesterfied FAs from the adipocytes are initiated by…

A

hormone sensitive lipase (HSL)

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26
Q

What are the final products of triacylglycerol hydrolysis?

A

glycerol

nonesterfied FAs

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27
Q

What is HSL activated by?

A
  • epinephrine
  • norepinephrine
  • ACTH
  • glucagon
  • acting via phosphorylation of enzyme
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28
Q

What is HSL inhibited by?

A

insulin

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29
Q

What are nonesterfied FAs bound to for transport to other tissues?

A

serum albumin

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30
Q

What are the major target tissues of nonesterfied FAs?

A

muscle and liver

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31
Q

How are nonesterfied FAs taken up at the target cells?

A

passively

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32
Q

What happens to the nonesterfied FAs when they are within the target cells?

A
  • found to fatty acid binding protein

- then must be activated

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33
Q

What type of cells are FAs taken up by?

A
  • cells where they may serve as precursors in the synthesis of other compounds
  • fuels for energy production
  • substrates for ketone body synthesis
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34
Q

When would FAs be exported to other tissues?

A

to be used for energy production

35
Q

What are ways FAs are synthesized for?

A

storage or export

36
Q

What occurs during FA activation

A

Fatty acid converted to fatty acyl CoAs

37
Q

What is the enzyme used during FA activation?

A

acyl CoA synthetases

38
Q

What are fatty acyl CoAs bound to to enter the mitochondria?

A

carnitine

Becomes acyl carnitine

39
Q

How does carnitine and acyl CoAs convert to acyl carnitine?

A

carnitine palmitoyl transferase I

40
Q

How is acyl carnitine transferred into the mitochondria?

A

acyl carnitine transporter

41
Q

What happens to acyl carnitine when it enters the mitochondria

A
  • becomes acyl carnitine + CoA-SH
42
Q

How does acyl carnitine separate in the mitochondria?

A

with CPTII

- becomes Acyl CoA + free carnitine

43
Q

What happens to the acyl CoA once in the mitochondria?

A

B-oxidation –> Acetyl CoA

44
Q

What is the end product of B-oxidation?

A

Acetyl CoA

45
Q

Where can B-oxidation occur?

A

mitochondria and peroxisomes

46
Q

What are the preferred substrates for peroxisomal B-oxidation?

A

very long chain FAs

47
Q

How many ATP are generated from one FA molecule?

A

106

48
Q

What are the types of oxidation of FAs?

A
  • a
  • b
  • w
49
Q

A-oxidation of FAs

A
  • Carbon atoms removed one at a time
50
Q

What is the end product of a-oxidation?

A

propionyl CoA

51
Q

Where does a-oxidation occur?

A

peroxisomes

52
Q

Where does w-oxidation occur?

A

microsomes

53
Q

What is w-oxidation carried out by?

A

CYP450 4A1

54
Q

w-oxidation of FAs

A
  • mono carboxylic FAs converted to dicarboxylic FAs

- then dicarboxylic FAs undergo b-oxidation

55
Q

Where are ketone bodies produced?

A

liver

56
Q

Where are ketone bodies used?

A

Peripherally as an energy source when glucose is not readily available

57
Q

What are ketone bodies synthesized from?

A

acetyl CoA

58
Q

Where does ketone body synthesis occur?

A

hepatic mitochondria

59
Q

Ketone body production

A
  • acetoacetate produced in three step process

- acetoacetate reduced to beta-hydroxy butyrate

60
Q

What is ketone body production regulated by?

A

availability of acetyl CoA

61
Q

When does the rate of ketone body production increase?

A

during starvation

62
Q

FA synthesis

A

process of combining 8 two C fragments to form a 16 C saturated FA (palmitate)

63
Q

What are the two C fragments combined during FA synthesis?

A

acetyl groups from acetyl CoA

64
Q

Palmitate and FA synthesis

A

Can be modified to give rise to other FAs

65
Q

What modifications can be done during FA synthesis?

A
  • chain elongation to give longer FAs

- desaturation: gives unsaturated FAs

66
Q

Where does FA synthesis occur?

A

primarily in cytoplasm of these tissues:

  • liver
  • adipose
  • CNS
  • lactating mammary gland
67
Q

What is the rate limiting step in the synthesis of FAs?

A

Acetyl CoA –> Malonyl CoA

68
Q

What is the enzyme used during the rate limiting step in the synthesis of FAs?

A

Acetyl CoA carboxylase

69
Q

FA synthase complex

A
  • acyl carrier protein
  • acetyl CoA-ACP transacetylase
  • Malonyl CoA-ACP transacetylase
  • B-ketoacyl-ACP synthase
  • B-ketoacyl-ACP reductase
  • B-hydroxyacyl-ACP dehydrates
  • Enoyl-ACP reductase
70
Q

What does one round of FA synthesis produce?

A

Butyryl-ACP (4C)

71
Q

When does the FA synthesis stop?

A

When 16C (palmitic acid) is produced

72
Q

What can happen to excess FAs in the liver?

A
  • plasma lipoproteins
  • B-oxidation
  • plasma free FAs
73
Q

Where can acetyl CoA go?

A
  • cholesterol
  • CAC
  • FAs in liver
  • ketone bodies in blood
74
Q

What is FA metabolism regulated by?

A

energy need of a cell

75
Q

What regulates the availability of glucose or FAs for use by a cell?

A

insulin

glucagon

76
Q

What happens during the fed state in the liver?

A
  • Insulin stimulates FA synthesis
  • Increases the levels of key enzymes
  • Insulin increases NADPH
  • Activating phosphorylation phosphatase
77
Q

What does the activation of phosphorylation phosphatase do?

A

dephosphorylates ACC

78
Q

What happens during the fed state in adipose tissue?

A
  • insulin promotes lipid storage
  • insulin increases glucose uptake by inducing Glut-4
  • glucose provides glycerol for TG biosynthesis
  • Insulin inhibits lipolysis
79
Q

What does the inhibition of lipolysis do?

A

dephosphorylates hormone sensitive lipase

80
Q

What happens during the fasted state in the liver?

A
  • insulin levels decrease
  • glucagon levels increase
  • FA synthesis decreases
  • Acyl CoA carboxylase inhibited by phosphorylation
  • Glycolysis decreases (reduces the supply of acetyl CoA)
  • Ketone body production increases
81
Q

What happens during the fasted state in the adipose tissue?

A
  • insulin levels decrease
  • glucagon levels increase
  • glucagon activates hormone sensitive lipase
  • adipose tissue lipolysis occurs
  • free FAs are delivered to liver, muscle, etc
82
Q

Regulation of FA oxidation during the fed state

A
  • FA oxidation decreases due to increased ACC activity
  • ACC produces malonyl CoA (precursor for new FAs)
  • Malonyl CoA also inhibits CPT-1
83
Q

What occurs during FA metabolism in the fasting state?

A
  • AT lipolysis
  • FA oxidation
  • ketone bodies
  • glycerol-gluconeogenesis
84
Q

What is excess FAs stored as during the fed state?

A

TAG in adipose