Lipids Flashcards

1
Q

What are the 4 biological roles of fatty acids?

A
  1. Building blocks for phospholipids and glycolipids
  2. Many molecules can be modified by the covalent attachment of fatty acids
  3. Fuel molecules stored as triglycerides
  4. Fatty acid derivatives can serve as second messengers or hormones
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2
Q

How does fatty acid degredation produce ATP?

A

It involves a series of oxidation reactions that convert fatty acids to acetyl CoA which can then be metabolised in the CAC to form energy and produce ATP.

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3
Q

Briefly describe the process of fatty acid synthesis:

A

The linkage of acetyl CoA and a malonyl unit and the process os repeated until C16 fatty acid is synthesised

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4
Q

What are the 4 processes of fatty acid degredation?

A
  1. Activated fatty acid is oxidised to introduce a double bond (FAD is reduced to FADH2. Occurs by a dehydrogenase enzyme
  2. Double bond is hydrated by a hydrotase enzyme which introduces a double bond
  3. hydroxyl group is oxidised to a ketone. NAD+ reduced to NADH. Done by a dehydrogenase enzyme
  4. Fatty acid is cleaved to form a activated acyl group (shortened by 2 carbons) and acetyl group (carbons). Done by a thiolase enzyme
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5
Q

Why are triglycerides such highly concentrated energy stores?

A

They are highly reduced. They are non polar so are stored in a nearly anhydrous form.

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6
Q

Describe the process of how lipids are ingested and how they get into the tissues:

A

They are ingested as glycerols, degraded to fatty acids for absorption across the intestinal epithelium by lipases. Triacylglycerides are are resynthesised in the epithelium, then packaged into lipoprotein transport particles called chylomicrons which eventually meet the blood. Adipose tissue and muscle then degrade the triacylglycerides back into fatty acids and glycerol for transport in the tissue. In the tissues triacyl glycerides are resynthesised and stored

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7
Q

What does lipases do?

A

They catalyse hydrolysis of bonds between the fatty acyl group and glycerol of triacylglycerol.

Triacyl glycerol (lumen of small intestine) + lipase - diacylglycerol + lipase - monoacylglycerol (muscosal cell)

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8
Q

What are the 3 steps as to how fatty acids can be used as a fuel source once they are in the tissues?

A
  1. Lipids must be mobilised/transported
  2. Fatty acids must be activated and transported to mitochondria
  3. Fatty acids must be broken down to acetyl coA
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9
Q

Describe the step of using fatty acids as a fuel source: Lipids must be mobilised/transported

A

Once they arrive in adipose tissue they need to be hydrolysed in a process called lipolysis (triacylgerol to fatty acids and glycerol). It is activated by epinephrine and glucagon and inhibited by insulin. The activation induces lipases to convert the triacylgerol to fatty acids and glycerol. They fatty acids are then released from adipose tissues and transported to energy requiring tissues. As fatty acids are not soluble they need to be transported in the blood by binding to serum albumin.

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10
Q

Describe the step of using fatty acids as a fuel source: activated and transported to mitochondria

A

Fatty acids must be activated and transported to the mitochondria for degredation. Fatty acid oxidation occurs in the mitochondrial matrix, but in order to enter the mitochondria, the fatty acid must first be activated through the formation of a thioester linkage to co enzyme A. ATP drives the formation of the thioester linkage between the carboxyl group of the fatty acid and the sulphydrol group of coA. This reaction takes place in the outer mitochondrial matrix and is catalysed by acetyl CoA in 2 steps. Carnitine carries long chain fatty acids into the mitochondrial matrix

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11
Q

Describe the step of using fatty acids as a fuel source: fatty acids broken down to acetyl CoA

A

Fatty acids are broken down in a step by step fashion:

Oxidation (FAD) - hydration - oxidation (NAD+) - thiolysis (CoA)

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12
Q

The degredation of palmitoyl coA (C16) requires how many reaction cycles to produce 2 acetyl CoA’s?

A

7

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13
Q

What is the reaction sequence for 1 palmaotyl coA?

A

Palmitoyl CoA + 7FAD + 7NAD+ + 7CoA + 7H2O = 8 acetyl coA + 7 FADH2 + 7NADH + 7H+

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14
Q

How many total ATP does the degredation of 1 molecule of palmitoyl CoA produce?

A

106

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15
Q

When are ketone bodies formed?

A

They are formed from acetyl CoA when fatty acid breakdown predominates. The acetyl CoA can only enter the CAC if carbohydrate and fat metabolism is appropriately balanced. In conditions where this is not the case, i.e fasting or diabetes.

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16
Q

What are 2 examples of ketone bodies?

A

Acetoacetate and B-3-hydroxybuterate

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17
Q

What happens during starvation?

A

Ketone bodies are synthesised in the liver and circulate to various tissues where they act as important sources of energy

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18
Q

What are 3 tissue types that can use ketone bodies?

A
  1. Brain
  2. Heart muscle
  3. Renal cortex
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19
Q

Compare the plasma levels of glucose, ketone bodies and fatty acids on day 1 of starvation compared to day 8:

A

Day 1: glucose is highest, then fatty acids then ketone bodies
Day 8: ketone bodies are highest, then glucose then fatty acids

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20
Q

What 2 tissues are able to synthesise fatty acids?

A

Liver and adipose

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21
Q

When is fatty acid synthesis required?

A

During embryonic development and lactation in mammary glands

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22
Q

What contributes to the fact that alcoholics get liver failure?

A

They cannot appropriately synthesise fatty acids

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23
Q

What is the precursor for fatty acid synthesis?

A

Acetyl CoA

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24
Q

Where can acetyl CoA come from?

A

Glycolysis or FA degredation

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25
What are the 3 main steps of FA synthesis?
1. Acetyl coA needs to be transported from the mitochondria to the cytoplasm 2. Linkage of 2x2 carbon units 3. Palmitate converted to other FA
26
Where does FA degredation take place?
Mitochondrial matrix
27
Where does FA synthesis take place?
Cytosol
28
Intermediates in FA synthesis are covalently linked to:
Sulphydrol groups of an acyl carrier protein ACP
29
Intermediates in FA degredation are covalently linked to:
Sulphydrol group Coenzyme A
30
Compare the enzymes of FA synthesis to those of FA degredation:
In synthesis they are collectively called FA synthase but in degredation, they are not related
31
What is the reductant in FA synthesis?
NADPH
32
What are the oxidants in FA degredation?
FAD and NAD+
33
What is ACP?
Acyl carrier protein - single polypeptide chain of 77 amino acids that can be regarded as a giant prosthtic group - a macro CoA
34
What is the committed step in FA synthesis?
The formation of malonyl CoA because it is irreversible
35
Name the enzyme and reaction in step 1 of FA synthesis:
Enzyme - acetyl CoA carboxylase | Acetyl CoA + ATP + HCO3- = malonyl CoA + ADP + Pi + H+
36
Name the enzyme and reaction in step 2 of FA synthesis:
Transacylase | Acetyl CoA + ACP = Acetyl ACP + CoA
37
Name the enzyme and reaction in step 3 of FA synthesis:
Transacylase | Malonyl CoA + ACP = Malonyl ACP + CoA
38
Name the enzyme and reaction in step 4 of FA synthesis:
Synthase | Acetyl ACP + Malonyl ACP = acetoacetyl ACP + ACP + CO2
39
Name the 4 types of reactions that happen during FA synthesis:
1. Condensation 2. Reduction 3. Dehydration 4. Reduction
40
What carries the acetyl groups from the mitochondria to the cytoplasm for FA synthesis?
Citrate
41
As citrate transports acetyl CoA to the cytoplasm, what else is produced?
One mole of NADPH is generated for each mole of acetyl CoA that is transferred.
42
FA synthesis requires 14 molecules of NADPH, where do the additional 6 come from?
Pentose phosphate pathway
43
What is the major product of FA synthesis?
Palmitate
44
In eukaryotes, longer chain FA are formed by elongation reactions that occur where?
In the cytosolic face of the ER
45
What are the 2 ways that acetyl CoA carboxylase is regulated?
1. By allostery | 2. By hormones
46
What are the 2 types of allosteric regulation of acetyl CoA carboxylase?
By citrate | By palmitoyl CoA
47
Describe the allosteric regulation of acetyl CoA carboxylase by citrate:
An increase in citrate when both acetyl CoA and ATP are high signals raw materials and energy are available for FA synthesis. Leads to increased FA synthesis
48
Describe the allosteric regulation of acetyl CoA carboxylase by palmatoyl CoA:
Will be abundant when there is an excess of FA. Therefore leads to a decrease in FA synthesis
49
Describe the hormonal regulation of acetyl CoA carboxylase by glucagon and epinephrine:
Inhibit fatty acid synthesis, inhibit the carboxylase by stimulating its phosphorylation by AMP activated protein kinase
50
Describe the hormonal regulation of acetyl CoA carboxylase by insulin:
Stimulates FA synthesis, by activating the carboxylase and stimulating the removal of the phosphate i.e stimulating the protein phosphatase
51
What is aracnadonate?
A FA which is a major precursor for many signalling molecules
52
What does cholesterol do?
It is an important component of membrane and moderates fluidity and it is the precursor for many signalling molecules such as steroid hormones
53
Where is the major site of cholesterol synthesis?
Liver
54
Where was cholesterol first discovered?
In gallstones
55
How much cholesterol can an adult on a low cholesterol diet synthesise per day?
800 grams per day
56
How is cholesterol degraded?
It cannot be degraded because the cells cannot degrade the nucleus so it must be excreted by the liver as bile or used in biochemical reactions
57
What is the structure of cholesterol?
27 carbon atoms
58
What are the 3 stages of cholesterol synthesis?
1. Synthesis of isopentenyl pyrophosphate - an inactivated isopropene that is the key building block of cholesterol (cytoplasm) 2. The condensation of 6 molecules of isopentenyl pyrophosphate to form squalene (ER) 3. The cyclization of squaline in a reaction and the tetracyclic product is then converted into cholesterol (ER)
59
Describe the stage of cholesterol production: stage 1
Acetyl CoA and acetoacetyl CoA form HMG-CoA (soluble) which is then reduced to mevalonate . Mevalonate is then converted to isopentenyl pyrophosphate in 3 reactions requiring ATP. This is is done by HMG-CoA reductase
60
What is the committed step in cholesterol formation?
The synthesis of mevalonate
61
What are the 4 ways that HMG - reductase is regulated?
1. The rate of synthesis of the reductase mRNA 2. The rate of translation of the reductase mRNA 3. The rate of degredation of the reductase 4. Phosphorylation of the reductase decreases its activity
62
What is the type of drug that inhibits HMG-reductase to reduce heart disease and how does it work?
Statin drugs - because HMG is soluble and it can also make other things like acetoacetate a ketone body. So if it is blocked, it can be metabolised through another pathways.
63
What is another way of managing cholesterol?
Inhibit the intestinal reabsorption of bile salts which are cholesterol derivatives themselves, that promote the absorption of dietary cholesterol and fats. Eat positively charged polymers that bind to negatively charged bile salts and they themselves are not absorbed
64
How is cholesterol transported in the body?
In lipoproteins which consist of a core of hydrophobic lipids surrounded by a shell of more polar lipids and proteins. They can shift between classes as they release or pick up cargo, thereby changing their density
65
What is the role of low density lipoproteins?
Cholesterol transport - B100
66
What is the role of high density lipoproteins?
Reverse cholesterol transport
67
What do apoporoteins do?
They solublize hydrophobic lipids | Contain cell targeting signals
68
LDL?
Low density lipoproteins - b100 - transport
69
What is he primary source of cholesterol outside the liver and intestine (i.e not synthesis)?
LDL - through receptor mediated endocytosis
70
What is the role of B100?
B100 is an apolipoprotein that is found on the outside of LDL and mediates binding to the receptor
71
How is the LDL complex taken up by the cell?
Receptor LDL complex is internalised by endocytosis and is now sitting in an endosome.
72
What happens after the endosome is formed?
The pH in the endosome drops by the use of a proton pump. And the receptor releases the LDL. The receptor can either be recycled or degraded
73
After the pH drops in the endosome then what happens?
The endosome fuses with a lysosome (full of enzymes) 1. The protein component (e.g B100) is hydrolysed and this results in free amino acids 2. The cholesterol ester is also hydrolysed by lipase resulting in free cholesterol and is used in membrane biosyntheses or reesterified to form a cholesterololeate ester that can then be stored inside the cell.
74
Once in the lysosme, how is the LDL released from the receptor?
The change in pH results in a change in shape of the receptor and this releases LDL
75
What keeps the receptor extended from the membrane so that the LDL binding region is available to LDL?
O-linked carbohydrates which function as struts
76
Which domains on the LDL receptor are most important for LDL binding?
Domains 4,5
77
Which part of the receptor is most important in LDL releasing?
The propeller structure
78
What does the absence of LDL receptors lead to?
Hypercholesterolaemia and artherosclerosis (heart disease)
79
Describe the difference between homozygotes and heterozygotes in terms of heart disease?
Homo - no functional LDL receptors and most die during childhood Hetero - 1/2 functional LDL receptors and get premature heart disease and die in 30’s or 40’s
80
If you have a disease that results in the failure of the receptor to release the LDL particle, what happens?
The receptor is lost by degredation
81
What are bile salts?
Polar derivatives of cholesterol and they function as detergents. They are synthesised in the liver and stored in the gall bladder
82
When was it discovered that adults too had brown fat?
2009
83
Where is brown adipose tissue normally found?
In babies and small animals to maintain body temp
84
Describe the shivering thermogenesis:
Involuntary muscle contraction so all mammals exposed to cold will eventually shiver to elevate heat production. In adult humans it can reach intensities equivalent to 40% of maximum O2 consumption and involves the oxidation of carbs and lipids.
85
Describe the non-shivering thermogenesis:
Brown adipose fat produces heat when activated by cold exposure. Being exposed to the cold results in massive blood flow to brown adipose tissue (highly vascularised)
86
What are 3 reasons as to why BAT can be used to combat obesity:
1. It can take up and store FA and glucose 2. By targeting glucose and FA as fuels, BAT may be able to mitigate the weight gain caused by sugars and HFD 3. FA may be stored as TG’s, oxidised or utilised to activate thermogenesis via UCP-1
87
What are the three types of adipose tissues?
White Brown Brite
88
What are the 5 main features of white adipose tissue?
``` Stores energy Low mitochondria No UCP-1 Pro-inflammatory Obesity ```
89
What are the 4 main features of brown adipose tissue?
Dissipates energy High mitochondria UCP-1 Anti-obestiy
90
Why can brown adipose tissue dissipate energy in the form of heat?
UCP-1 causes a proton leak across the inner mitochondrial membrane of the mitochondria therefore dissipating chemical energy in the form of heat. Brown fat adipocytes are inefficient for ATP production but energy sufficient for heat production.
91
What is an example of a drug that causes all energy to be lost as heat and is a diet pill?
Dinitrolphenol
92
In brown tissue activation, what is the stimulus and what does it stimulate?
Noradreneline stimulates the B adronergic receptors which leads to increased cAMP.
93
What does activation of the B adronergic receptor by noradreneline result in?
Uptake of substrates from the circulation - free fatty acids and glucose.
94
What does the increased cAMP result in?
It stimulates the expression of a deiodenase enzyme (D2) that converts T4(thyroxine) to the active hormone T3 (triothyroxine)
95
Where is BAT found in adult humans?
In little pockets along the shoulders and between the shoulder blades More in slimmer people, people that live in cold Less in old people
96
What does the activation of T3 do?
Stimulates UCP-1 and increased loss of energy as heat
97
The browning of adipose tissue is an ____ and _____ response to environmental challanges:
Adaptive and reversible (with thermoneutraitly - HFD)
98
What is the dominant transcriptional regulator of BAT development?
PRDM16 - antiobesity and increase thermogenesis
99
Describe the process by which capsinoids (spicy) and cold exposure promote anti obesity:
Capsinoids bind to capsinoid receptors in the gut. The signal from this receptor and the cold sensation from the skin is transmitted to WAT deposits through the B adrenergic receptor. Signals stimulate BAT adipogenesis through the receptor and stabilization of the transcription factor PRDM16 protein
100
What is cancer associated cachxia?
A syndrome characterised by inflammation, body weight loss, atrophy of adipose tissue and skeletal muscle wasting
101
Cachxia is responsible for:
20% of total deaths from cancer
102
What is a possible treatment of Cachxia?
Inhibition of WAT browning
103
Describe what happens to WAT in a patient with Cachxia:
Their WAT browns which leads to high energy expensiture. Systemic inflammation and Il-6 induce and sustain WAT browning. They have the UPC-1 protein in WAT
104
Describe the browning of white adipose tissue in burn victims:
Burn injury results in increased ciculation of norepinephrine which results in increased UCP-1, increased mitochondria and oxidative capacity in white adipose tissue. This is because the skin has lost a insulating skin barrier so the body needs to produce more heat to keep a normal body temp.