Lipid Metabolism Flashcards

1
Q

Lipids can be broken down structurally into two main classes:

A

1) Those based on fatty acid structure
2) Those based on isoprenoid (cholesterol) structure

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2
Q

Two naming conventions are commonly used to describe fatty acid structure

A

Examples: 18:4Δ6,9,12,15 and 18:4 (ω-3)

Both describe a fatty acid with 4 double bonds in the same place

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3
Q

18:4Δ6,9,12,15
Number of carbons =
number of double bonds =
first carbon of each db, counting from acid end =

A

18 = number of carbons

4 = total number of double bonds (db)

6,9,12,15 = first carbon of each db, counting from acid end

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4
Q

18:4 (ω-3)
___ = number of carbons
___ = total number of double bonds (db)
____ = first carbon of first db, counting from the methyl end

A

18 = number of carbons
4 = total number of double bonds (db)
ω(omega)-3 = first carbon of the first db is 3 counting from the methyl end (carbon 1 end)

Each subsequent db is then 3 carbons away
Unlike the previous naming convention, these subsequent carbons are not included in the name

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5
Q

18:4 and 18:4 (ω-3) are the _____ fatty acid

A

same

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6
Q

Double bonds can be ___ or ____

A

cis or trans

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7
Q

The ____ form creates a “bend” in the structure. What do you think
Does this do to membrane fluidity?

A

cis
- creates more fluidity
- lowers the melting point

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8
Q

is saturated solid or liquid at body temperature?

A

solid - rigid structure

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9
Q

Do cis bonds allow for tighter or looser packing of phospholipids?

A

looser packing
= increased fludiity

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10
Q

which fatty acid is the most naturally made fats

A

Cis

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11
Q

what are the two sources of trans fats?

A

Some are made naturally by bacteria in the gut of ruminants, so found in meat products

Most are made commercially as a by-product of partial hydrogenation

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12
Q

Partial hydrogenation targets cis-bonds in fatty acids to:

A

Add hydrogens and turn oils into solid fats

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13
Q

_____ is a by-product of partial hydrogenation

A

Trans fats

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14
Q

How can partially hydrogenated fats be labelled as “0 trans fat” ?

A

Using reduced pressure and blending with oil reduces the trans fat content. Less than 0.5 grams per serving can be labelled as “0% trans fat”

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15
Q

which fat is associated with an increased risk of coronary heart disease?

A

Trans fats

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16
Q

where does fatty acid synthesis occur? Typically makes __:0 palmitate

A

Occurs in cytoplasm, typically makes 16:0 palmitate
- NO double bones

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17
Q

what two substrates are required for fatty acid synthesisn

A

Acetyl CoA and malonyl CoA

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18
Q

what is malonyl CoA?

A

Malonyl CoA is acetyl CoA with an extra CO2 group added

  • Malonyl CoA will prevent fatty acids from entering the mitochondria matrix where beta-oxidation takes place
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19
Q

what enzyme is responsible for fatty acid synthesis? How many fatty acid chains can be made at once?

A

Fatty acid synthase
- Enzyme complex, exists as a dimer

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20
Q

Fatty acid synthase contains two S groups: one from _____ and another from _____

A

Contains two S groups: one from cysteine, one from B5

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21
Q

Cysine binds _____ groups while B5 binds _____ group

A

Cys binds acetyl groups
B5 binds malonyl groups
These will combine to make one chain on each side of the enzyme

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22
Q

What 3 coenzymes are required for fatty acid synthesis

A

B7 (biotin)

B5

B3 (NADPH)

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23
Q

what role does coenzyme B7 play in fatty acid synthesis?

A

Helps add CO2 to acetyl CoA to make malonyl CoA

What do you think the enzyme’s name is?

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24
Q

what role does coenzyme B5 play in fatty acid synthesis?

A

part of fatty acid synthase - B5 binds malonyl groups

part of acetyl CoA and malonyl CoA (as CoA)

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25
Q

what role does coenzyme B3 (NADPH) play in fatty acid synthesis?

A

Reduces the fatty acid chain

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26
Q

Which pathway provides the NADPH?

A

pentose phosphate shunt

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27
Q

what are the 5 steps of fatty acid synthesis?

A

1) Acetyl group joins
2) Malonyl group joins
3) Acetyl and malonyl groups condense with loss of CO2
4) O removed as water, NADPH donates H’s
5) Fatty acid chain shifts over

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28
Q

during fatty acid synthesis, how do you get to a 16-carbon chain?

A

Keep repeating steps 2-4: what are they?

2) Malonyl group joins
3) Acetyl and malonyl groups condense with loss of CO2
4) O removed as water, NADPH donates H’s
5) Fatty acid chain shifts over

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29
Q

During fatty acid synthesis, how do you get the chain off the enzyme?

A

Use water to break the bond
Hydrolysis

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30
Q

during lactation, how is fatty acid synthesis different?

A

during lactation, short-chain fatty acids are made for the production of milk

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31
Q

How do you make the chain bigger than 16C?

A

Elongate using enzymes embedded in the ER membrane
- Process follows similar steps, but uses individual enzymes

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32
Q

where does the elongation of 16C fatty acids to 18C occur?

A

the ER membrane

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33
Q

are the vast majority of fatty acids even or odd?

A

even.
- odd numbers are usually from plants

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34
Q

how are odd-numbered fatty acid chains synthesized?

A

Starting with propionyl CoA (3 C) rather than acetyl CoA (2 C) in step one can make odd-numbered chains

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35
Q

How do you get unsaturated fatty acids?

A

Desaturase enzymes use NAD(P)H (B3) to create double
bonds

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36
Q

where can we make unsaturated fatty acids?

A

Some we can make in the ER

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37
Q

Some are “essential”, only get from diet. what is an example?

A

linoleic acid, 18:2 Δ9,12
- Δ12 and Δ15desaturase enzymes are only found in plants

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38
Q

what fatty acids are needed to support cardiovascular, immune,
reproductive and nervous systems

A

ω-3 and ω-6

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39
Q

where is omega 3 found?

A

ex: α-linolenic acid
High levels in fish

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40
Q

where is omega 6 found?

A

ex: linoleic acid
High levels in vegetable oils

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41
Q

Too many ω-_ in relation to ω-_ levels can promote inflammation, increase the risk of heart disease, etc. What is the optimal ration?

A

too much omega-6 in relation to omega-3

Optimal ratio around 1-4 : 1 for ω-6 : ω-3
- Typical Wester diet around 16 : 1

42
Q

why are omega 3 and omega 6 considered essential?

A

we cannot synthesize them

43
Q

How do you regulate fatty acid synthesis? (3)

A

Glucagon
Insulin
Epinephrine

44
Q

typically released when blood sugars levels are low

A

Glucagon
- indicates FAST state

45
Q

typically released when blood sugar levels are high

A

Insulin
- indicates FED state

46
Q

released during sympathetic (flight or fight) responses

A

Epinephrine

47
Q

Synthesis is ________ regulated to breakdown (beta ox). Synthesis promotes ______ of fats as TGs

A

oppositely - fatty acids are not made while they are being broken down

  • storage
48
Q

Glucagon and epinephrine _________ acetyl CoA carboxylase

A

inhibits

Decreased substrate for fatty acids = Decreased fatty acid synthesis

Increased transport of fatty acids into the mitochondria = Increased beta-oxidation

49
Q

Insulin _________ Activates acetyl CoA carboxylase

A

activates

Increased substrate for fatty acids = Increased fatty acid synthesis

Decreased transport of fatty acids into the mitochondria = Decreased beta-oxidation

50
Q

What does acetyl CoA carboxylase catalyze?

A

Acetyl-CoA carboxylases (ACCs) are enzymes that catalyze the carboxylation of acetyl-CoA to produce malonyl-CoA

51
Q

Triglycerides (aka triacylglycerols, TAGs, TGs) provide.. (2)

A

energy and insulation

52
Q

the middle fatty acid in TG will always be _________. Why?

A

Satruated, unsaturated, either saturated or unsaturated
We want it stored at oil

53
Q

Which packs tighter and therefore stores energy more efficiently: TG’s or glycogen? Why?

A

glycogen is very polar and will bind water

TG’s are non-polar and they will not bind to water
- they will pack together and therefore stores energy more efficiency

54
Q

Lipogenesis occurs in the liver and adipocytes..where? Cytosol or mitochondria?

A

Cytosol

55
Q

Starts with the addition of _ fatty acids to a glycerol backbone. Replace the phosphate on the backbone with the 3rd fatty acid chain

A
56
Q

Liver: What enzyme do you think adds a phosphate to glycerol?

A

Glycerol kinase (ATP involved)
- traps it in the cell

57
Q

Making the backbone review

Adipose and liver: Convert DHAP (from where?) to glycerol-3 phosphate using what enzyme?

A

Glycerol-3-phosphate dehydrogenase

58
Q

CoA is added to fatty acid in the cytosol to _____ it

A

trap it
- energizes it and makes it more water-soluble

Fatty acids are added to a CoA carrier using ATP

CoA acts to carry the fatty acid chains to the backbone
and transfer them over

59
Q

Diacylglycerol acyl transferase

A

slide 36

60
Q

Phosphatidic acid phosphatase

A

slide 37

61
Q

Phospholipids and glycosphingolipids both contain: (3)

A

1) A backbone
2) Lipid (may be part of backbone)
3) Head group

62
Q

Phosphoglycerides (aka glycerophospholipids) has

A

1) Glycerol backbone
2) 2 fatty acid chains

63
Q

Sphingolipids contain

A

1) Sphingosine backbone
2) Ceramide: sphingosine (includes a fatty chain), plus an additional fatty acid chain

Sphingomyelin
Cerebrosides
Gangliosides

  • found in the brain
64
Q

GLYCOSPHINGOLIPIDS contain

A

1) Sphingosine backbone
2) Ceramide: sphingosine (includes a fatty
chain), plus an additional fatty acid chain

Cerebrosides Gangliosides + a carbohydrate head group

65
Q

what does a phospholipid contain

A

1) Glycerol backbone
2) 2 fatty acid chains
3) Polar phosphate-alcohol head
- phosphatidate addition can be (polar head) -serine, -ethanolamine, -inositol, -choline

66
Q

Sphingomyelin is a PL that is a sphingolipid

A

Backbone = sphingosine
(part of ceramide)

has two fatty acid-like tails, but:
- One is part of the sphingosine backbone
- One is added to sphingosine to make a ceramide

67
Q

what are found in cell membranes, important component of myelin

A

Sphingolipids

68
Q

Cerebrosides and gangliosides are also __________ BUT they are not phospolipids

A

sphingolipids
their head group is carbohydrate

69
Q

what sphingolipid has a monosaccharide head group

A

Cerebrosides
- If additionally sulfated = sulfatide

70
Q

what sphingolipid has 1 or more sialic acid plus 1 or more
additional monosaccharides

A

Gangliosides

71
Q

SPHINGOLIPIDS has non-polar embedded in membrane and polar - faces the surface

A
72
Q

Accumulation of sphingolipids leads to sphingolipid storage diseases called

A

sphingolipidases

73
Q

GM2 accumulates in lysosomes due to an enzyme deficiency - cannot degrade them!!

A

G = ganglioside
M = # of sialic acids (ie one)
2 = pattern of monosaccharides in the head group

74
Q

Most severe excesses occur in the brain - Build-up leads to neuronal cell damage

A

Progressive neurodegeneration can lead to death by 5 years of age

75
Q

what is the purpose of glycosphingolipids?

A

regulate protein trafficking and signal transaction

76
Q

Eicosanoids: Derived from arachidonic acid (__:4) or similar ___C fatty acids

A

Eicosanoids: Derived from
arachidonic acid (20:4) or similar 20 C fatty acids

77
Q

Eicosanoids: Physiological functions depend on the type and include:

A

Vasodilation
Vasoconstriction
Platelet aggregation

  • there is a build-up, it can increase the risk of cardiac problems
78
Q

Mixtures of non-polar molecules, including fatty acids linked to long-chain hydrocarbon alcohols via ester bonds

A

Waxes
Wax esters are found in cerumen (ear wax), beeswax, etc

79
Q

every single cell in the body has ______

A

cholesterol
1:1 of phospholipid to cholesterol

80
Q

Categories of Isoprenoids: Isoprene units linked together. Sometimes in alcohol or aldehyde or ring form

A

Terpenes

81
Q

Smallest terpene = 2 isoprene units linked together =

A

monoterpene

82
Q

_________ = 4 isoprenes, triterpene = 6 isoprenes, etc

A

Diterpene

83
Q

Names of common terpenes
Farnescene = a _____terpene
Squalene = a ____terpene
Beta carotene = a _____terpene

A

Farnescene = a sesquiterpene

Squalene = a triterpene

Beta carotene = a tetraterpene

84
Q

Terpenes with a non-terpene component attached

A

Mixed Terpenes

85
Q

Examples of mixed terpenes:
CoQ (important in ____)
Vit. K (important in _____)
Farnesylated proteins (important in ________ _______)

A

CoQ (important in ETC)

Vit. K (important in clotting)

Farnesylated proteins (important in cell signalling)

86
Q

Complex molecules are made from 6 isoprene units. Contain four fused rings with various substituents

A

Steroids

87
Q

Steroids are made from _________

A

cholesterol

88
Q

Cholesterol synthesis: Starts with 3 of what molecules make which
intermediate?

A

3 X Acetyl CoA

makes HMG CoA

89
Q

Cholesterol synthesis: What is the rate-limiting enzyme?

A

HMG CoA to Mevalonate
catalyzed by HMG-CoA reductase

90
Q

what do statins do?

A

block HMG CoA to Mevalonate
- prevent the synthesis of cholesterol to a degree

91
Q

What isoprenoid is formed that is ultimately converted
to the cyclic structure of cholesterol?

A
92
Q

Most cholesterol synthesis occurs in the _____

A

Most cholesterol synthesis occurs in the liver

93
Q

The liver can use cholesterol to:

A
  • Make bile
  • Make lipoproteins (LDL, lipid part includes cholesterol) to carry cholesterol to the tissues
94
Q

_________ is a precursor to steroid hormones

A

Cholesterol is a precursor to steroid hormones

95
Q

Familial hypercholesteremia is an inherited defect in LDL receptors. What does this lead to?

A

an increase in circulating LDL, and therefore cholesterol, in the blood
- This increases risk of myocardial infarction

96
Q

Cholesterol is first converted to ______________, which is
then converted to various other steroid hormones

A

pregnenolone
- Hormones are made in specific tissues depending on the
enzymes that are expressed in those tissues

97
Q

Example of other steroids: which steroid hormones are made in testes and ovaries respectively

A

in the testes and ovaries, pregnenolone is made into Testosterone and estrogen

98
Q

Example of other steroids: which steroid hormone is made by adrenal glands to regulate stress responses

A

in the adrenal gland, pregnenolone is made into Cortisol to regulate stress response

99
Q

Cardiac glycosides are derivatives of ______ sterols

A

plant
Note the lipid attached to the carbohydrate: this is an
isoprenoid ring structure

100
Q

what is an example of a cardiac glycoside?

A

Digoxin
- used to manage and treat heart failure certain arrhythmias, and abortion.

101
Q

what type of sterol can compete with intestinal cholesterol absorption?

A

Plant sterols. They have a similar structure to cholesterol

Helps lower LDL cholesterol levels