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
what role does coenzyme B3 (NADPH) play in fatty acid synthesis?
Reduces the fatty acid chain
26
Which pathway provides the NADPH?
pentose phosphate shunt
27
what are the 5 steps of fatty acid synthesis?
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
28
during fatty acid synthesis, how do you get to a 16-carbon chain?
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
29
During fatty acid synthesis, how do you get the chain off the enzyme?
Use water to break the bond Hydrolysis
30
during lactation, how is fatty acid synthesis different?
during lactation, short-chain fatty acids are made for the production of milk
31
How do you make the chain bigger than 16C?
Elongate using enzymes embedded in the ER membrane - Process follows similar steps, but uses individual enzymes
32
where does the elongation of 16C fatty acids to 18C occur?
the ER membrane
33
are the vast majority of fatty acids even or odd?
even. - odd numbers are usually from plants
34
how are odd-numbered fatty acid chains synthesized?
Starting with propionyl CoA (3 C) rather than acetyl CoA (2 C) in step one can make odd-numbered chains
35
How do you get unsaturated fatty acids?
Desaturase enzymes use NAD(P)H (B3) to create double bonds
36
where can we make unsaturated fatty acids?
Some we can make in the ER
37
Some are “essential”, only get from diet. what is an example?
linoleic acid, 18:2 Δ9,12 - Δ12 and Δ15desaturase enzymes are only found in plants
38
what fatty acids are needed to support cardiovascular, immune, reproductive and nervous systems
ω-3 and ω-6
39
where is omega 3 found?
ex: α-linolenic acid High levels in fish
40
where is omega 6 found?
ex: linoleic acid High levels in vegetable oils
41
Too many ω-_ in relation to ω-_ levels can promote inflammation, increase the risk of heart disease, etc. What is the optimal ration?
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
why are omega 3 and omega 6 considered essential?
we cannot synthesize them
43
How do you regulate fatty acid synthesis? (3)
Glucagon Insulin Epinephrine
44
typically released when blood sugars levels are low
Glucagon - indicates FAST state
45
typically released when blood sugar levels are high
Insulin - indicates FED state
46
released during sympathetic (flight or fight) responses
Epinephrine
47
Synthesis is ________ regulated to breakdown (beta ox). Synthesis promotes ______ of fats as TGs
oppositely - fatty acids are not made while they are being broken down - storage
48
Glucagon and epinephrine _________ acetyl CoA carboxylase
inhibits Decreased substrate for fatty acids = Decreased fatty acid synthesis Increased transport of fatty acids into the mitochondria = Increased beta-oxidation
49
Insulin _________ Activates acetyl CoA carboxylase
activates Increased substrate for fatty acids = Increased fatty acid synthesis Decreased transport of fatty acids into the mitochondria = Decreased beta-oxidation
50
What does acetyl CoA carboxylase catalyze?
Acetyl-CoA carboxylases (ACCs) are enzymes that catalyze the carboxylation of acetyl-CoA to produce malonyl-CoA
51
Triglycerides (aka triacylglycerols, TAGs, TGs) provide.. (2)
energy and insulation
52
the middle fatty acid in TG will always be _________. Why?
Satruated, unsaturated, either saturated or unsaturated We want it stored at oil
53
Which packs tighter and therefore stores energy more efficiently: TG’s or glycogen? Why?
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
Lipogenesis occurs in the liver and adipocytes..where? Cytosol or mitochondria?
Cytosol
55
Starts with the addition of _ fatty acids to a glycerol backbone. Replace the phosphate on the backbone with the 3rd fatty acid chain
56
Liver: What enzyme do you think adds a phosphate to glycerol?
Glycerol kinase (ATP involved) - traps it in the cell
57
Making the backbone review Adipose and liver: Convert DHAP (from where?) to glycerol-3 phosphate using what enzyme?
Glycerol-3-phosphate dehydrogenase
58
CoA is added to fatty acid in the cytosol to _____ it
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
Diacylglycerol acyl transferase
slide 36
60
Phosphatidic acid phosphatase
slide 37
61
Phospholipids and glycosphingolipids both contain: (3)
1) A backbone 2) Lipid (may be part of backbone) 3) Head group
62
Phosphoglycerides (aka glycerophospholipids) has
1) Glycerol backbone 2) 2 fatty acid chains
63
Sphingolipids contain
1) Sphingosine backbone 2) Ceramide: sphingosine (includes a fatty chain), plus an additional fatty acid chain Sphingomyelin Cerebrosides Gangliosides - found in the brain
64
GLYCOSPHINGOLIPIDS contain
1) Sphingosine backbone 2) Ceramide: sphingosine (includes a fatty chain), plus an additional fatty acid chain Cerebrosides Gangliosides + a carbohydrate head group
65
what does a phospholipid contain
1) Glycerol backbone 2) 2 fatty acid chains 3) Polar phosphate-alcohol head - phosphatidate addition can be (polar head) -serine, -ethanolamine, -inositol, -choline
66
Sphingomyelin is a PL that is a sphingolipid
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
what are found in cell membranes, important component of myelin
Sphingolipids
68
Cerebrosides and gangliosides are also __________ BUT they are not phospolipids
sphingolipids their head group is carbohydrate
69
what sphingolipid has a monosaccharide head group
Cerebrosides - If additionally sulfated = sulfatide
70
what sphingolipid has 1 or more sialic acid plus 1 or more additional monosaccharides
Gangliosides
71
SPHINGOLIPIDS has non-polar embedded in membrane and polar - faces the surface
72
Accumulation of sphingolipids leads to sphingolipid storage diseases called
sphingolipidases
73
GM2 accumulates in lysosomes due to an enzyme deficiency - cannot degrade them!!
G = ganglioside M = # of sialic acids (ie one) 2 = pattern of monosaccharides in the head group
74
Most severe excesses occur in the brain - Build-up leads to neuronal cell damage
Progressive neurodegeneration can lead to death by 5 years of age
75
what is the purpose of glycosphingolipids?
regulate protein trafficking and signal transaction
76
Eicosanoids: Derived from arachidonic acid (__:4) or similar ___C fatty acids
Eicosanoids: Derived from arachidonic acid (20:4) or similar 20 C fatty acids
77
Eicosanoids: Physiological functions depend on the type and include:
Vasodilation Vasoconstriction Platelet aggregation - there is a build-up, it can increase the risk of cardiac problems
78
Mixtures of non-polar molecules, including fatty acids linked to long-chain hydrocarbon alcohols via ester bonds
Waxes Wax esters are found in cerumen (ear wax), beeswax, etc
79
every single cell in the body has ______
cholesterol 1:1 of phospholipid to cholesterol
80
Categories of Isoprenoids: Isoprene units linked together. Sometimes in alcohol or aldehyde or ring form
Terpenes
81
Smallest terpene = 2 isoprene units linked together =
monoterpene
82
_________ = 4 isoprenes, triterpene = 6 isoprenes, etc
Diterpene
83
Names of common terpenes Farnescene = a _____terpene Squalene = a ____terpene Beta carotene = a _____terpene
Farnescene = a sesquiterpene Squalene = a triterpene Beta carotene = a tetraterpene
84
Terpenes with a non-terpene component attached
Mixed Terpenes
85
Examples of mixed terpenes: CoQ (important in ____) Vit. K (important in _____) Farnesylated proteins (important in ________ _______)
CoQ (important in ETC) Vit. K (important in clotting) Farnesylated proteins (important in cell signalling)
86
Complex molecules are made from 6 isoprene units. Contain four fused rings with various substituents
Steroids
87
Steroids are made from _________
cholesterol
88
Cholesterol synthesis: Starts with 3 of what molecules make which intermediate?
3 X Acetyl CoA makes HMG CoA
89
Cholesterol synthesis: What is the rate-limiting enzyme?
HMG CoA to Mevalonate catalyzed by HMG-CoA reductase
90
what do statins do?
block HMG CoA to Mevalonate - prevent the synthesis of cholesterol to a degree
91
What isoprenoid is formed that is ultimately converted to the cyclic structure of cholesterol?
92
Most cholesterol synthesis occurs in the _____
Most cholesterol synthesis occurs in the liver
93
The liver can use cholesterol to:
- Make bile - Make lipoproteins (LDL, lipid part includes cholesterol) to carry cholesterol to the tissues
94
_________ is a precursor to steroid hormones
Cholesterol is a precursor to steroid hormones
95
Familial hypercholesteremia is an inherited defect in LDL receptors. What does this lead to?
an increase in circulating LDL, and therefore cholesterol, in the blood - This increases risk of myocardial infarction
96
Cholesterol is first converted to ______________, which is then converted to various other steroid hormones
pregnenolone - Hormones are made in specific tissues depending on the enzymes that are expressed in those tissues
97
Example of other steroids: which steroid hormones are made in testes and ovaries respectively
in the testes and ovaries, pregnenolone is made into Testosterone and estrogen
98
Example of other steroids: which steroid hormone is made by adrenal glands to regulate stress responses
in the adrenal gland, pregnenolone is made into Cortisol to regulate stress response
99
Cardiac glycosides are derivatives of ______ sterols
plant Note the lipid attached to the carbohydrate: this is an isoprenoid ring structure
100
what is an example of a cardiac glycoside?
Digoxin - used to manage and treat heart failure certain arrhythmias, and abortion.
101
what type of sterol can compete with intestinal cholesterol absorption?
Plant sterols. They have a similar structure to cholesterol Helps lower LDL cholesterol levels