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Phase 2 3. Endocrinology > Lipid disorders and metabolism > Flashcards

Lipid disorders and metabolism Flashcards

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1
Q

What are the dietary lipids

A

Triglycerides
Cholesterol
Phospholipids

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2
Q

Describe the sturcture of triglicerides

A

3 FA chains attached to a glycerol backbone by an ester bond

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3
Q

What are the sources for maintaining plasma TAG/FFA

A

> FA synthesis
Dietary lipids
TAG in adipose tissue

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4
Q

What processes do plasma TAG/FFA contribute to?

A

> Production of ketone bodies
beta-oxidation (ATP production)
Phospholipid synthesis for membranes
Stored as TAG in adipose tissue

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5
Q

Where are lipids digested?

A

Lipid digestion occurs in the small intestine

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6
Q

What enzymes are required for lipid digestion?

A

Pancreatic lipase and colipase

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7
Q

What is the clinical importance of enzymes used in lipid digestion?

A

Lipase is a target for orlistat

Orlistat acts as a lipase inhibitor, preventing fat absorption and limits calorie intake

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8
Q

What is the emulsifying agent required in lipid digestion?

A

Bile salts

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9
Q

Where are bile salts secreted?

A

Through the bile duct by the liver

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10
Q

What are bile salts synthesised from?

A

Cholesterol

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11
Q

What is the function of bile salts?

A

To emulsify fats into micelles

Increase surface area for the enzymes to work on, increasing efficiency of digestion

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12
Q

What are bile acids conjugated form?

A

Taurine/glycine

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13
Q

How are lipids absorbed?

A

As chylomicrons transported to liver, adipose tissue removed the lipid component (FA stored as TAG) leaving cholesterol-rich chylomicron remnant

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14
Q

When will there be more chylomicrons?

A

post-prandial period for absorption of dietary lipids

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15
Q

When will there be fewer chylomicrons

A

During fasting state

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16
Q

How is TAG transported?

A

In lipoproteins

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17
Q

How is FFA transported?

A

Albumin-bound

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18
Q

What is the purpose of lipoproteins?

A

To transport lipids safely

- prevents loose fatty acids acting as detergents in the circulation

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19
Q

What is NEFA?

A

Nonesterified fatty acids

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20
Q

Why are NEFA transported in chylomicrons?

A

Need to be transported in chylomicrons as they are dangerous - could break down cell walls

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21
Q

What is beta oxidation?

A

The generation of energy from fatty acids

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22
Q

Where does beta oxidation occur?

A

Within the mitochondrion

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23
Q

What is the function of CoA in fatty acyl-CoA

A

Addition of CoA to form fatty acyl-CoA
- Traps FFA within the cell (same principle as G6P)

CoA makes FFA soluble and removes the danger of detergent action

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24
Q

How does fatty acyl-CoA cross the inner mitochondrial membrane?

A

Requires carrier molecule carnitine, as mitochondrion unable to transport fatty acyl-CoA

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25
Where can you find a high carnitine content?
In the muscle
26
How does carnitine transport fatty acyl-CoA across the inner mitochondrial membrane?
Carnitine palmitoyl transferase (CPT) as catalysts Carnitine swaps with CoA to form FA carnitine + CoA via CPT 1 This is swapped back via CPT 2
27
What happens to fatty acyl-CoA in beta-oxidation?
Fatty acyl-CoA are degraded by oxidation at the b-carbon Process occurs in rounds reducing chain by 2 carbons each time 2 carbons removed and used to make acetyl CoA
28
What are the products of beta oxidation?
Each turn produces 1 FADH2, NADH and acetly CoA (2 carbons)
29
How is ATP produced as a result of beta-oxidation?
Acetyl CoA if further oxidised to yield ATP - TCA/oxidative phosphorylation
30
What is the benefit of using beta-oxidation?
High yield of ATP - C16 yields 106 ATP vs 36 for glucose Fatty acids excellent source of ATP Fatty acids can be stored densely ATP also available from glycerol backbone
31
How are triglycerides synthesised?
Through the esterification of 3 fatty acids and glycerol
32
What are the main enzymes involved in triglyceride synthesis?
> Lipoprotein lipase | > Diacylglycerol Acyl Transferase
33
What is the role of Lipoprotein lipase?
Hydrolyses circulating TAG in chylomicrons/VLDL Extracellular enzyme
34
What is the role of Diacylglycerol Acyl Transferase?
Re-esterifies FFA and glycerol to TAG Intracellular enzyme
35
How is glycerol obtained?
From glycolysis - DHAP | Normally synthesised from glucose rather than breakdown of TAG
36
What is lipolysis?
The breakdown of triglyceride into glycerol and 3 fatty acids
37
What enzyme has an important role in lipolysis?
Hormone sensitive lipase in adipose tissue
38
What are the regulatory measures for hormone-sensitive lipase?
Activated by cAMP-dependent phosphorylation in response to adrenaline in fasted state Inhibited by insulin by stimulating cAMP breakdown
39
Describe lipolysis
Adipose tissue is highly innervated with noradrenergic nerves (release NA) In fasting -> release NA, raising intracellular cAMP and causing activation of PKA -> phosphorylates and activates HSL to stimulate lipolysis
40
When does lipolysis occur?
In the fasted state
41
What happens to the products of lipolysis?
FFA are delivered to the liver for gluconeogenesis?
42
What tissue type like FFA as a fuel?
Muscle, particularly red fibres
43
How are fatty acids synthesised?
From glucose | Built 2C at a time (max 16C)
44
What are the regulatory enzymes in fatty acid synthesis?
Acetyl CoA carboxylase (ACC) | Fatty acid synthase
45
What is the role of Acetyl CoA carboxylase (ACC)?
Forms malonyl CoA (3C structure) Malonyl CoA also inhibits FA oxidation -> prevents FA oxidation while FA are being synthesised, as this would waste energy Reciprocal regulation
46
How is Malonyl CoA formed?
By Acetyl CoA carboxylase (ACC) ``` Uses biotin (vitamin b7) deficiences are rare, but will cause disregulation of lipid metabolism ```
47
How does Malonyl CoA inhibit FA oxidation?
> Acetyl CoA is coupled to malonyl CoA - uses energy that would otherwise produce ATP > 7 consecutive steps by multifunctional enzyme - Fatty acid synthase > Requires NADPH (pentose phosphate pathway) > Occurs in cytoplasm
48
Why are ketones produced?
Ketone formation is an "overflow" pathway for acetyl CoA use if there is not enough oxaloacetate for acetyl CoA to enter krebs
49
What dietary condition leads to ketone formation?
Diets with very low carbohydrate content
50
What are ketone bodies?
3 water soluble molecules produced by the liver from fatty acids >Acteoacetate > beta hydroxybutyrate > Acetone
51
How are ketone bodies formed?
Acetyl CoA + Acetyl CoA => acetoacetyl CoA acetoacetyl CoA - CoA => Acetoacetate Acetoacetate can be converted to acetone and beta hydroxybutrate
52
What tissues use ketone bodies as an energy source?
The brain | The heart
53
How are phospholipids synthesised?
Same as beginning steps of triglyceride synthesis to form DAG, which is then combined with an alcohol From this you get different phospholipids
54
What are the different phospholipids formed?
``` Phosphatidylethanolamine Phosphatidylserine Phosphatidylglycerol Phosphatidylinositol Phosphatidylcholine ```
55
Which cells have high levels of phospholipid synthesis?
Rapidly-dividing cells as they have to make lots of membranes NB - potential target for new cancer drugs?
56
What are essential fatty acids?
Fatty acids that cannot be synthesised Obtained from the diet (originally classed as vitamin F) Polyunsaturated w-3 or w-4 (depends on location of double c-c bond on fatty acyl chain)
57
What are the functions of essential fatty acids?
Cell membrane formation Required for proper growth and development Required for brain and nerve function Precursors for eicosanoids - prostanoids & leukotrienes - in inflammatory response
58
What is the link between w-3 fatty acids and CVD?
some evidence for protection against hear and circulatory disease reduces plasma TAG
59
What is the link between w-6 fatty acids and CVD?
May lower low-density lipoprotein (LDL) Some evidence that high levels may lower HDL (detrimental effect)
60
What are the hormones regulate lipid metabolism?
Insulin and noradrenaline
61
How does insulin regulate lipid metabolism?
Stimulates FA synthesis, TAG synthesis Suppresses lipolysis ``` Insulin stimulates: > GLUT4-mediated transport of glucose > Acetyl CoA carboxylase activity > Increases expression of FAS > Increases activity of LPL (in adipose only) ``` Inhibition of lipolysis by: stimulates breakdown of cAMP
62
How does noradrenaline regulate lipid metabolism?
Stimulates lipolysis Noradrenaline stimulates: > cAMP synthesis > cAMP-dependent protein kinase (PKA) activation > PKA-mediated phosphorylation and activation of HSL
63
What are the levels of LPL in different tissues in the fed state?
increased LPL synthesis and activity in adipocytes | decreased LPL synthesis and activity in skeletal and heart muscle
64
What are the levels of LPL in different tissues in the fasted/exercised state?
decreased LPL synthesis and activity in the adipocytes | increased LPL synthesis and activity in the muscle
65
What are potential affects of elevated FA with obesity?
Lipolysis is overactive and adipose storage capacity for TAG is exceeded FA are taken up and stored in liver and possibly muscle
66
How can elevated FA levels lead to the development of T2DM?
Metabolites of FA impair insulin signalling, driving the extreme insulin resistance that causes diabetes - primarily cause by impact in the liver Causes impaired insulin action in liver, adipose and muscle - increased lipolysis, gluconeogenesis - decreased glucose uptake, glycogen synthesis Excess FA may also directly impair insulin secretion by the beta cell Hyperglycaemia results

Phase 2 3. Endocrinology (25 decks)

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