Lipid Metabolism L16 L17 Flashcards
(200 cards)
1
Q
what is a lipid
A
chemically diverse group of compounds which are not soluble in water but soluble in non-polar organic solvents – contain
2
Q
how are lipids usually related to fatty acids
A
they contain fatty acids or they are made from fatty acids
3
Q
is cholestrol a lipid
A
Cholestrol is a sterol, but many regard it as a lipid and does not contain fatty acid but can attach to a fatty acid
4
Q
problem of lipid transport around the body
A
not soluble in water – problem when transporting around the body in blood, plasma of the blood is water based so lipids wont dissolve in it
5
Q
what is a fatty acid
A
long hydrocarbon chain (containing carbon & hydrogen) with a terminal carboxyl (COOH) group
6
Q
what is the general formula of a fatty acid
A
CH3(CH2)nCOOH
n is a variable number
7
Q
how many carbons do fatty acids in plants and humans have
A
even number of carbons
8
Q
how many carbons do fatty acids in bacteria usually have
A
Uneven usually produced by bacteria
9
Q
why can we sometimes have uneven number carbon fatty acids
A
we can ingest bacteria, these an end up in our tissues (animals don’t make them)
10
Q
what forms of fatty acids are there in the body
A
triacylglycerol phospholipids free fatty acids glycolipids cholesterol ester
11
Q
what is triacylglycerol
A
fat
adipose tissue
12
Q
what is the biggest amount of lipid in the body
A
triacylglycerol
13
Q
what is adipose tissue importance
A
biggest store of energy, cant survive without it
14
Q
what are phospholipids
A
major component of all membranes
15
Q
what do the most abundant phospholipids in the body contain
A
have a glycerol backbone, have two fatty acids attached to them and on third carbon of glycerol is phosphate and alcohol group
16
Q
what are free fatty acids
A
Non-Esterified fatty acids (NEFA) not attached to anything
plasma
17
Q
what are glycolipids
A
carbohydrate and lipid
18
Q
what is cholesterol ester
A
cholesterol with fatty acid attached to it, storage form
19
Q
what is the fatty acid level like in the blood when we awake before eating
A
before eating when wake up will be high level
When not eating and asleep, no stimulation to produce insulin, fat tissue starts to break down some reserves and break down some triglycerol release non-esterified fatty acids
20
Q
what happens to the fatty acid level in the blood when we consume food after sleeping
A
after eaten will lower due to regulation of fatty acid release due to insulin
soon as eat insulin rises, turn off enzyme e which breaks down the fat and levels of fatty acid go down
21
Q
what are the major biological roles of fatty acids
A
energy storage and production
protection/insulation
biological membranes
precursors of other bioactive molecules
22
Q
why is it important to have energy storage and production
A
if couldn’t do this our meals would have to match our requirements exactly – would have to graze all day release excess stored energy
23
Q
what provides protection and insulation - fatty acids
A
triacylglycerol
24
Q
what is the importance of phospholipids in membranes
A
isolate cell/organelles from outside environment
allow communication with outside environment (not completely sealed)
protect from outside, keep certain molecules in and others out
25
what bioactive molecules are fatty acids precursors of
eicosanoids
26
what are examples of eicosanoids
prostaglandins
prostacyclins
thromboxanes
leukotrienes
27
what are eicosanoids
all are local hormones, immediate effect on cell itself or cells surrounding it
28
what is the structure of triacylglycerols
Esters of 3 Fatty Acids with glycerol backbone
29
what is the structure of phospholipids
Esters of 2 Fatty acid with glycerol backbone
| 3rd carbon of glycerol attached to a phosphate group + another alcohol (often containing nitrogen)
30
what are the three fatty acids like that are attached to the triacylglycerol
Rare for the three fatty acids to be the same only usually happens if artificially manufactured triacyglycerols for any reason they want to have it completely homogenous
31
what is triacylglycerol like at room temperature
Triacyglycerol that was a long chain of saturated fatty acids very solid at room temp
32
what are unsaturated fatty acids like at room temperature
Unsaturated fatty acids are flexible at room temperature – give membranes flexibility (when talking about phospholipids too)
33
how can fatty acids differ
```
chain length
number of double bonds
* none = saturated
* 1 = monounsaturated
* >1 = polyunsaturated
position on the chain of the double bonds
type of double bonds (cis and trans)
```
34
how many carbons do most fatty acids have
16-18
35
what double bond if mainly found in nature
cis
36
what double bond is mainly found in bacteria
trans
37
why would we sometimes have trans double bond fatty acids in our body
if we ingest bacteria with them
38
what is a cis double bond
carbons both on the same side
39
what is a trans double bond
carbons on opposite sides
40
how can trans double bonds be formed
Can get trans fatty acids by chemically hydrogenating fat
41
why is a cis bond fatty acids fluid at room temperature
Cis bond put bend in the fatty acid, so fluid at room temp
42
why is a trans bond fatty acid solid at room temperature
Trans bond has a straight chain, behaves more like a fatty acid, solid at room temperature
43
what effect is there is a cis bond is changed to a trans bond
changes the nature and the biological properties
44
how can fatty acids be named
```
- if start from carboxyl end
name them based on the number of double bonds
carbon length
- if start from the methyl end
which omega family they're in
```
45
what does omega-x- denote in naming fatty acids
Omega-x- denotes the position of the first double bond from the orange end
methyl end
46
what does delta-x- denote in naming fatty acids
Delta-x- similar to systematic in that it describes the position of double bonds from the carboxyl end
47
which end should we name from in fatty acids if we want to put it into a 'family'
methyl
| will group into omega 3, 6, 9
48
what family would fatty acids from methyl end with first double bond from the third be in
omega 3
49
what are all polyunsaturated fats made from
monounsaturated fatty acids by further desaturations (more double bonds)
50
what fatty acids can can animals make
only major ones animals can make de novo are based on oleic acid
51
what effect do animals have on fatty acids
insert double bonds between existing bond and carboxyl group
52
where do we get linoleic acid and alpha-linolenic acids from
Plants can make both linoleic acid and alpha-linolenic acid we can consume these as we need them, we can change them when they’re in out body
can’t make linoleic acid or α-linolenic acid from oleic acid enzymes cant put the double bond the other side of the existing double bond, it has to be from the carboxyl end
53
what effect do plants do to fatty acids
insert double bonds between existing bond and methyl group
54
what are fatty acids important for
Play a vital role in membrane function
| Are the precursors of eicosanoids
55
what are MUFA
mono unsaturated fatty acids
56
what are PUFA
poly unsaturated fatty acids
57
how does 2C acetyl CoA go to 3C
Acetyl CoA carboxylase enzyme adds another carbon onto acetyl CoA to make malonyl CoA
58
how does 3C malonyl CoA go to 16C
Fatty acid synthase enzyme adds two carbons to make palmitic acid
59
how does 16C palmitic acid go to 18C
Elongase enzyme adds two carbons to make stearic acid
60
how does 18C go to 18C with a double bond (monounsaturated)
Delta9-desaturase enzyme insert double bond to make oleic acid
61
when is ATP produced from acetyl CoA
Produce ATP when acetyl CoA broken into CO2 – need energy
62
how is acetyl CoA transported into the cytosol
Acetyl CoA itself wont cross mitochondrial membrane, have to temporarily make it into citrate molecule by combining it with oxaloacetate
Specific transporter lets citrate across membrane
When citrate on other side it is broken down again to get acetyl CoA
Oxaloacetate is broken back down into pyruvate which moves back into the mitochondria
63
where is acetyl CoA made
mitochondria
64
where are fatty acids synthesised
cytosol
65
what mechanism is used to transport acetyl CoA
So need to get it out the mitochondria by using a shuttle mechanism
66
in fatty acid synthesis what is the rate limiting enzyme
Acetyl CoA carboxylase, first step which regulates the rate at which fatty acids are made
67
what is the fatty acid synthesis of prokaryotes
synthesis occurs due to the action of a series of separate enzymes
68
what is the fatty acid synthesis of eukaryotes
synthesis occurs through the action of a multifunctional enzyme complex
69
what is linked to acyl carrier protein
Intermediates in fatty acid synthesis
70
what is ACP
acyl carrier protein
71
what is ACP in bacteria
77 amino acid protein joined to a phosphopantetheine (PP) group
72
what is ACP part of in animals
part of the fatty acid synthase complex
73
what is the acetyl transacylase reaction
Acetyl CoA joins with ACP temporarily form acetyl ACP+CoA
74
what is the malonyl transacylase reaction
Malonyl CoA joins with ACP temporarily form malonyl ACP+CoA
75
what does fatty acid synthase system do
synthesizes long chain saturated fatty acids
76
what does the fatty acid synthase system involve in prokaryotes
four separate enzymes
77
what are the substrates in fatty acid synthase
Acetyl-ACP
Malonyl-ACP
NADPH
78
what are the steps in the fatty acid synthase reaction
Start with acetyl ACP 2C fatty acid, reacts with malonyl ACP 3C, requires reducing power from 2 NADPH molecules
NADPH oxidized to make NADP+
One of the carbons from malonyl CoA lost as CO2
Lose some water
2 carbons from malonyl-ACP added to acetate to make butryl-ACP 4 C
79
what process occur in the fatty acid synthase reaction
1. Condensation
2. Reduction
3. Dehydration
4. Reduction
80
what happens in chain elongation
Every step added another two C
| Lose a C as CO2
81
what is chain termination
uses a water from synthesis of palmitate
| carbon chain tend to stop at C16, release palmitic acid
82
what releases palmitic acid in chain termination
thioesterase enzyme
83
where are shorter chains usually released (chain termination)
Some shorter chain fatty acids are also released, particularly in mammary gland
84
what is the major product of fatty acid synthase reaction
palmitic acid
85
how many carbon atoms are in 60% of fatty acids
60% of fatty acids in human adipose tissue have 18 Carbon atoms
86
where are fatty acids from
Diet (plants and animals)
Further metabolism of palmitate - Can further elongate palmitate and add extra two carbons and make 18 carbon fatty acids
87
where is palmitic acid made
cytoplasm
88
where is stearic acid made
Some of the palmitic acid moves to the endoplasmic reticulum
Palmitic acid to stearic acid, adding two extra carbons using elongase occurs on endoplasmic reticulum
89
where is oleic acid made
Also on endoplasmic reticulum stearic acid made into oleic acid, delta9–desaturase acts on the ninth carbon from carboxyl end and can insert double bond between ninth and tenth carbon probably
90
what is the most abundant fatty acid in nature
Oleic acid
91
name some important1-acyl glycerol phosphate 2-acyltransferase phospholipids
phosphatidylcholine
phosphatidylethanolamine
phosphatidylserine
phosphatidylinositol
92
what are phospholipids important in
major components of biological membranes
| role in cell signalling
93
what is the difference in the first step of triacylglycerol and phospholipids synthesis
they're the same
glycerol-3-phosphate converted to lysophosphatidate
a fatty acid, which is attached to Co factor Co enzyme A
Release fatty acid from Co enzyme A and join it to the first carbon
G-3-P produces lysophosphatidate (added a fatty acid on first carbon)
Often is a saturated fatty acid added on first carbon
94
what are glycerol-phospholipids
all phospholipids with glycerol backbone
95
what is phosphidate
Phosphatide is a glycerol with two fatty acids, one on first carbon, second on second carbon
96
what happens to lysophosphatidate in triacylglycerol and phospholipid synthesis
Fatty acid joined to Co enzyme A, released from enzyme and fatty acid joins to second carbon
97
what does triacylglycerol and phosphoplipid synthesis start with
Normally start with a glycerol that has phosphate on third carbon – glycerol-3-phosphate
98
what can happen to phosphatidate
can take 2 routes phosphatide can take
Can remove phosphate group from third carbon using phosphatidate phosphohydrolase enzyme, so replaced with hydroxyl group – diacylglycerol
Take nucleotide CTP, and CDP molecule added to last carbon form CDP-diacylglycerol
99
what causes the different routes for phosphatidate
Depending on the metabolic state of the cell, and requirements of cell which is made
100
how can phosphatidate form triacylgylcerol
Form diacylglceryol by adding another fatty acid to last carbon to form triacylglycerol
101
what does diacylgylcerol make
Phosphotidylcholin and Phosphotidylethanolamine phospholipids, these make Phosphotidylserine
102
what does CDP-diacylgylcerol form
Phosphotidylinostitol
103
what does phosphidate form
diacylglycerol
| CDP-diacylglycerol
104
what happens in lipid transport
eat them, digest and absorb them need to move fatty acids round body to different tissues often directly to adipose tissue
Plasma of blood is water based media
Transport out of intestine
105
why is it important to be able to store
need to be able to mobilise that energy when fasting as a source of energy
106
where are lipids made
Store and make lipids in liver, then has to mobilise and transport them
107
where are lipids stored
adipose tissue
108
where are lipids used
muscles
109
where are triacylglycerols stored
Adipose tissues
110
what are NEFA
non-esterified fatty acids
111
what happens with non-esterified fatty acids in lipid transport
NEFA can be released from adipose tissue and loosely stick to protein, albumin –major protein in blood produced by the liver, has hydrophobic regions on it which fatty acids seek out and temporarily attach to transported to muscle and released. Taken into muscle cells and used as energy source
112
what happens with intestine and liver in lipid transport
Intestine and liver make complicated particles – lipoproteins. Is a sphere, ball shaped lipoprotein has a coating of phospholipids hydrophilic due to the polar heads being on the outside, so will physically dissolve in the plasma
113
what is a lipoprotein like
Hydrophobic fatty acid tail on inside
molecules of cholesterol dotted in the outer coating
Lipids inside that don’t like water e.g. triacylglycerol extremely hydrophobic
114
what is cholesterol ester like
very hydrophobic
115
what are the components of lipoproteins
proteins - apolipoproteins
phospholipids - phosphatidylcholine most abundant
triacylglycerol
cholesterol and cholesterol ester
116
where is cholesterol in lipoproteins
free cholesterol at surface
117
where is cholesterol ester in lipoproteins
attached to fatty acid in core
118
how do lipoprotein classes differ
protein/lipid ratio
phospholipid/cholesterol/cholesterol ester/ triacylglycerol ratio
specific proteins present
119
how do physical difference occur in lipoprotein
size
Density (chylomicrons big but light as full of lipid)
Charge (depends which proteins they have, can separate individual lipoproteins using gel electrophoreis)
120
which lipoproteins are not named by classification
Lipoproteins produces by intestine not named by classification, these are the chylomicrons
121
why do many chylomicrons float
are less than 1 density so float
| water is 1
122
what is VLDL
very low density liopoprotein
| density lessthan 1.006
123
what is IDL
intermediate density lipoprotein
124
what is LDL
low dense lipoprotein
125
what is HDL
high dense lipoprotein
126
why must those who's lipid profile is being measure told to not to eat
chylomicrons are hard to completely seperate from VLDL
127
what are apolipoproteins
diverse group of proteins that associated with lipoproteins
128
how come apolipoproteins can jump around different molecules
most proteins are only loosely associated with surface
129
what are the apolipoproteins functions
structural
enzyme activators or inhibitors
receptor recognition
130
what are the apolipoproteins structural function
Hold particle together
| e.g. ApoB48 & ApoB100
131
what are the apolipoproteins enzyme activators or inhibitors function
e.g. Apo CII – activates lipoprotein lipase/ ApoCIII - inhibits lipoprotein lipase
132
what are the apolipoprotein receptor recognition functions
Recognised by receptors on the surface of cells
| e.g. ApoB100 recognised by LDL receptor
133
what does e.g. B48 in a apolipoprotein mean
B48 is 48% of the size of B100
134
which lipoprotein is the most simple
LDL as only has B100
135
what are the lipoprotein synthesis and secretion paths
exogenous path
endogenous path
reverse cholesterol transport path
136
what happens in the exogenous path of lipoprotein metabolism
Dietary fats mainly fatty acids leave intestine in a chylomicron released into lymphatic system, enter blood stream, catches chylomicron, anchored to it
enzyme breaks triacylglycerol inside and release fatty acids
Chylomicron delivers a lot of its fat to adipose tissue, producing chylomicron remnants
Chylomicron remnant is delivered to the liver
137
what happens in the endogenous path of lipid metabolism
VLDL released from liver into circulation, pass into capillaries of tissues, interacts with lipoprotein lipase, either in muscle or adipose tissue
VLDL acted on lipoprotein lipase, breaks down triacylglycerol inside it, releases fatty acids and migrate to tissues
Remnant particle of VLDL is IDL, half of the IDL directly removed
138
how can heart disease be caused
Some LDL can be deposited in arteries = bad, causes heart disease
139
what happens in the reverse cholesterol transport path
Nascent HDL grows round the body and picks up cholesterol and delivers it to liver
Liver takes large amounts of cholesterol
Tissues cant break cholesterol
140
where is VLDL made
liver
141
where does most VLDL get directed
most VLDL will be directed to muscle rather than adipose tissue
142
how is the remnant IDL removed in lipoprotein metabolism - endogenous
circulates through the liver (50% removed from liver by interacting with receptors) and other 50% is acted on by another enzyme hepatic lipase, which is in the liver further breaks it to LDL
Of the LDL 80% circulates back to the liver and is removed and the other 20% taken up by peripheral tissues
143
what is crucial in regulating LDL
Liver is crucial in regulating how much LDL is in the blood
144
why is there competition in lipoprotein metabolism
Competition for LDL between these two paths
| Both occur simultaneously
145
what is the tissue of origin for exogenous
intestine
146
what is the tissue of origin for endogenous
liver
147
what is the exogenous particle
chylomicron
148
what is the endogenous particle
VLDL
149
what is the site os secretion for exogenous
lymph/blood
150
what is the site of secretion for endogenous
blood
151
what is the exogenous ApoB form
apoB48
152
what is the endogenous ApoB form
apoB100
153
what is the exogenous remnant
chylo remnant
154
what is the endogenous remnant
IDL/LDL
155
what is the site is uptake for exogenous
liver
156
what is the endogenous site of uptake
liver/peripheral
157
what is the exogenous receptor
LRP/LDL
158
what is the endogenous receptor
LDL
159
what is the exogenous ligand
apoE
160
what is the endogenous ligand
apoE/apoB100
161
what is LCAT
lecithin:cholesterol-acyl transferase
162
what shape is newly formed HDL
disc-shaped
163
what happens when cholesterol and phospholipid combine
use LCAT enzyme
form
- cholesterol ester
- lysophospholipid
164
how is HDL converted to spherical HDL
Cholestrol ester moves to center of the partical (as hates water)
and becomes a spherical lipoprotein
165
when does HDL3 become HDL2
HDL3 continues to accumulate cholesterol ester and makes HDL2
HDL moves round body getting more cholesterol
HDL2 goes to liver when cant physically collect more, then liver can make them into e.g. bile acids, then excreted in faeces, major way to remove cholesterol
166
how is cholesterol removed from HDL2
HDL2 will associate to the liver and pump the cholesterol ester into the liver, shrinks to become HDL3 and then goes to collect more cholesterol ester
167
what happens to fatty acids when they get into cells
adipose tissue
liver
muscle
168
what happens to fatty acids in adipose tissues
stored as triacylglycerol (energy source)
169
what happens to fatty acids in liver
form either
- triacylglycerol phospholipid
- acetyl CoA which forms CO2 and ketone bodies
170
what happens to fatty acids in muscle
acetyl CoA forms CO2
| In the fast state/starved can used acetyl CoA, feed into TCA cycle to make energy it needs
171
what energy is used in fed state
will mainly use glucose
172
when is ketone bodies made
if starving the acetyl CoA may be used to make ketone bodies as an alternative fuel for body
In starvation fatty acids can be used for ketogenesis to make ketone bodies
173
what is adipocyte
adipose tissue
174
what is the structure of fatty acid in adipose tissue
Big droplet of lipid in centre of cell cytoplasm tends to be pushed towards the outside, nucleus often pushed against plasma membrane
175
what causes liver disease
when obese resistant to insulin, so cant break down the lipid droplets – main cause of liver disease
176
what happens to fatty acids in fasted state
most FA will go muscle
177
where does and what is glycogenesis
Liver capable of taking glucose and fructose made into sugar glycogenesis
178
how can the liver use fatty acids in liver to get energy
Liver can use some for beta oxidation to get some energy
Fatty acids fed into beta-oxidation, breaking down fatty acid to acetyl CoA then used in TCA cycle to get ATP
179
what is the alternative energy source for muscles
muscle use fatty acids
| if low glucose
180
in fed state what is the fatty acid metabolism in muscle
in fed state can be from chylomicrons
| In both the fed and fat state can be from VLDL, fatty acids released by lipoprotein lipase
181
in the starved state what is the fatty acid metabolism in muscle
can be from non-esterified fatty acid released through adipose tissue
182
what are the three sources of fatty acids for energy
Released by LPL from chylomicrons
Released by LPL from VLDL
Released as NEFA from adipose tissue
183
what is the overall energy yield from palmitic acid
106 ATP
184
what is the site in the cell of fatty acid synthesis
cytosol
185
what is the carrier molecule of fatty acid synthesis
ACP
186
what is the site in the cell of fatty acid oxidation
mitochonria
187
what is the carrier molecule of fatty acid oxidation
CoEnzyme A
188
what is the enzymes fatty acid synthesis
multifunctional enzyme
189
what is the enzymes fatty acid oxidation
separate enzymes
190
what is the carbon units fatty acid synthesis
2C added from (3C) malonyl-CoA
191
what is the carbon units fatty acid oxidation
yields (2C) acetyl-CoA
192
what is the CoFactor of fatty acid synthesis
uses NADPH
193
what is the CoFactor of fatty acid oxidation
yields NADPH, can feed into electron transport chain
194
what is the fatty acid metabolism in the liver
Liver can receive FA from chylomicron remnants
newly synthesized fatty acids through lipogenesis
Can take fatty acids and re-esterify them and package them into VLDL and secrete them, if this system becomes overloaded then can store fat as little droplets in its own cells, fine as a temporary measure, will mobilise the fat again when don’t need it
195
what happens in fatty acid oxidation
linked to CoA before degradation
Need to link fatty acids back to Co enzyme A using acyl CoA synthase using up a molecule of ATP, to generate a lot more
196
how is acyl-CoA formed
fatty acids enter cytosol of cell, move into mitochondria
temporary shuttle, using molecule carnitine
catalyzed by CPT
Acyl CoA temporarily breaks down, fatty acid group is attached to a carnitine, transports it across mitochondrial membrane
Another Co enzyme A reattaches it to fatty acid, releasing carnitine, which can go back into cytoplasm and reused
Once in mitochondira beta-oxidation can start
197
what is the first stage in fatty acid oxidation
two CH2 molecules
oxidation, removal of hydrogen
generates FADH2 from FAD (energy can be fed into electron transport chain)
198
what is the second stage of fatty acid oxidation
add water – hydration, break double bond and add hydroxyl group to first carbon in double bond and hydrogens on second
199
what is the third stage of fatty acid oxidation
another oxidation
NADH2 forms from NAD (more energy that can feed into electron transport)
Broken down hydroxyl group and replaced with double bond, leading to an oxygen
Ready to release some carbons in the form of acetyl CoA
200
what happens in the last stage of fatty acid oxidation
release second carbon in and original carboxyl group
C=O becomes new carboxyl group and Co enzyme A comes in and joins it
produce FA that’s got two less carbons, continue till broken down whole of fatty acid, all carbons released as acetyl CoA
