Lecture 4: Lipid Metabolism Flashcards

1
Q

Where is fatty acid metabolized?

A

Mitochondria

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2
Q

Once taken up by the cell, what are fatty acids used for?

A

1) Precursor for synthesis of other compounds
2) Energy production
3) Substrate for ketone body synthesis

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3
Q

What is the major form of energy storage?

A

Fat

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4
Q

What is the structure of acetyl CoA?

A

Acetyl group and Coenzyme A

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5
Q

What does Coenzyme A consist of?

A
  • Beta-mercaptoethylamine
  • Pantothenic acid (not synthesized in man = an essential nutrient)
  • Phosphate
  • 3’, 5’-adenosine diphosphate
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6
Q

What is the structure of a fatty acid?

A

1) A long hydrocarbon chain
2) A carboxylic acid group

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7
Q

What is the length of a hydrocarbon chain in a fatty acid? What is the most common length?

A

The chain length ranges from 4 to 30 carbons; 12-24 is the most common.

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8
Q

What is the shape of a fatty acid?

A

linear

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9
Q

Carbons in a fatty acid are always _____.

A

even

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10
Q

How many double bonds does a saturated fatty acid have?

A

0 double bonds

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11
Q

What are examples of a saturated fatty acid?

A

stearic acid and palmitic acid

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12
Q

How many double bonds does a monosaturated fatty acid have?

A

1 double bond

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13
Q

What is an example of a monosaturated fatty acid?

A

Oleic acid

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14
Q

What configuration is a double bond in a fatty acid?

A

Cis configuration

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15
Q

Fatty acids with how many double bonds are most prevalent in the human body?

A

Fatty acids with 1 double bond

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16
Q

How do carbons appear in a polyunsaturated fatty acid?

A

3 carbon intervals
Ex: -C=C-C-C=C-

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17
Q

How many double bonds are in a polyunsaturated fatty acid?

A

2 or more double bonds

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18
Q

What is an example of a polyunsaturated fatty acid?

A

Linoleic acid

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19
Q

Polyunsaturated fatty acids are NEVER _____.

A

conjugated

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20
Q

What type of bridge does a polyunsaturated fatty acid create?

A

Methylene bridge

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21
Q

What plays a significant role in the melting point of fatty acids?

A

Steric hindrance = causes backbone to bend

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22
Q

The more double bonds in fatty acids = ______ melting point

A

lower

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23
Q

Which type of fatty acid has a high melting point and is solid?

A

Saturated fatty acid

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24
Q

Which carbon in a fatty acid is the 1st carbon?

A

Carboxyl/carbonyl carbon

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25
Q

Which carbon in a fatty acid is the alpha carbon?

A

Carbon next to the carboxyl/carbonyl carbon

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26
Q

Which carbon in a fatty acid is the beta carbon?

A

Carbon next to alpha carbon

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27
Q

Which carbon in a fatty acid is the omega carbon?

A

The last carbon in the chain, farthest away from the carboxyl carbon

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28
Q

Which fatty acids are essential to humans (must obtain from diet)?

A

Linoleic acid and Linolenic acid

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29
Q

Where does fatty acid synthesis occur?

A

Cytoplasm of these tissues:
Liver, adipose (fat), CNS, lactating mammary gland

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30
Q

What are the products of acetyl CoA?

A

1) triglycerides
2) phospholipids
3) eicosanoids
4) energy (ATP)
5) ketone bodies
6) cholesterol (bile salts and steroid hormones)

31
Q

Where does acetyl CoA for fatty acid synthesis come from?

A

Mostly from glycolytic breakdown of glucose

32
Q

What is the major source of acetyl CoA for fatty acid synthesis?

A

Glucose

33
Q

What are the conditions that are conducive to fatty acid synthesis?

A

The ratio of insulin:glucagon is high

34
Q

What is the net equation of fatty acid de novo synthesis?

A

8 acetyl CoA + 7 ATP + 14 (NADPH + H+) (right arrow) palmitate (16:0) + 8 CoA + 7 (ADP + Pi) + 14 NADP+ + 6 H2O

35
Q

What is the rate-limiting step in fatty acid de novo synthesis?

A

Acetyl CoA carboxylase w/biotin

36
Q

Acetyl CoA carboxylase requires ______ as a cofactor.

A

biotin

37
Q

Which isoforms of acetyl CoA carboxylase (ACC) occur in the liver?

A

ACCʆ and ACCβ

38
Q

Which isoform of acetyl CoA carboxylase (ACC) occurs in skeletal muscle?

A

ACCβ

39
Q

Which isoform of acetyl CoA carboxylase (ACC) occurs in adipose tissue?

A

ACCʆ

40
Q

Which isoform of acetyl CoA carboxylase (ACC) occurs in the heart?

A

ACCβ

41
Q

What are the mechanisms used for the short-term regulation of ACC?

A

Phosphorylation (inactive) and phosphorylation (inactive)

42
Q

When ACC is phosphorylated it is _____.

A

inactive

43
Q

When ACC is dephosphorylated it is ______.

A

active

44
Q

Phosphorylation _____ ACC activity.

A

inhibits

45
Q

Which enzymes phosphorylate ACC?

A

AMP-dependent protein kinase & Protein Kinase A

46
Q

What activates AMP-dependent protein kinase & Protein Kinase A which phosphorylates ACC?

A

Activated by high glucagon

47
Q

Which enzyme dephosphorylates ACC?

A

phosphoprotein phosphatase

48
Q

What activates phosphoprotein phosphatase which dephosphorylates ACC?

A

Activated by high insulin

49
Q

What is a positive effector of ACC in allosteric regulation (long-term)?

A

Citrate = activation

50
Q

What is a negative effector of ACC in allosteric regulation (long-term)?

A

Long-chain fatty acids = inhibition

51
Q

What does ChREBP stand for?

A

Carbohydrate-Responsive Element Binding Protein

52
Q

What is ChREBP?

A

a major glucose-responsive transcription factor

53
Q

Where is the expression of ChREMP induced and why is it induced?

A

Induced in liver in response to increased glucose uptake

54
Q

ChREBP acts synergistically with which protein?

A

Sterol Response Element Binding Protein (SREBP)

55
Q

What happens when ChREBP acts synergistically with SREBP?

A

Induces lipogenic genes such as ACC and fatty acid synthase

56
Q

What happens to ChREBP when glucose (basal) concentrations are low?

A

ChREBP is phosphorylated and resides in the cytosol

57
Q

What happens to ChREBP when glucose levels are high?

A

ChREBP is dephosphorylated and translocates to the nucleus where it binds to Carbohydrate Response Elements (ChoREs) to stimulate transcription of lipogenic genes

58
Q

What happens to ChREBP when glucose levels are normal?

A

ChREBP is phosphorylated but will not activate lipogenic genes in the cytosol which will not produce fatty acids

59
Q

What enzyme elongates/lengthens fatty acids?

A

Fatty acid elongase

60
Q

Fatty acid elongase uses _____ ____to add 2 carbons at a time in the ______.

A

Acetyl CoA, mitochondria

61
Q

Fatty acid elongase uses _____ ____to add 2 carbons at a time in the ______.

A

malonyl CoA, microsomal (ER)

62
Q

Fatty acid elongase elongates the chain from the ____.

A

front

63
Q

Do acetyl CoA carbons increase or decrease the carbon #?

A

increase

64
Q

Where does fatty acid desaturase occur and what does it do?

A

Occurs in ER and is required to introduce double bonds

65
Q

What reduces fatty acid desaturase?

A

NADH

66
Q

What are the 4 distinct desaturases?

A

∆9, ∆6, ∆5, ∆4 (act on the 9th, 6th, 5th, or 4th carbons)

67
Q

What is the minimum chain length required for desaturation?

A

16-18 carbons

68
Q

Which desaturase is the main desaturase?

A

∆9

69
Q

Elevated levels of which fatty acid is an indication of essential fatty acid deficiency?

A

Mead acid = 20:3 ∆ 5,8,11

70
Q

What deficiency causes scaly dermatitis?

A

Essential fatty acid synthesis

71
Q

What is the major storage form of fat?

A

Triaclyglycerides

72
Q

What are the primary organs of triacylglyceride synthesis?

A

liver and adipose cells

73
Q

What is the major fatty acid synthesized de novo?

A

Palmitate

74
Q

List the lipogenic genes

A

1) Acetyl-CoA carboxylase
2) Fatty acid synthase
3) ATP citrate lyase
4) Glucose-6-phosphate dehydrogenase
5) 6-phosphoglucoronate dehydrogenase
6) Malic enzyme
7) Fatty acid desaturase