Lecture 8: Lipid metabolism + Disorders

Question 1

Name the 3 dietary lipids that are present in our diet

Answer 1

1. Triglycerides- the majority of the lipids from our diet.
2. Cholesterol - present in our diet but we do not need it as we make 2/3rds of our cholesterol
3. Phospholipids- from the membranes from the cells we eat

Question 2

Describe the general structure of a triglyceride

Answer 2

3 fatty acids attached to a glycerol molecule by ester bonds

Question 3

Name the 3 types of fatty acids?

Answer 3

1. Saturated- no double bonds.
2. Monosaturated- one double bond
3. Polyunsaturated - more than one double bond.

Note: a trigylyceride molecule can mix and match which fatty acids it has (does not need the be the exact same 3 fatty acids e.g. 2 monosaturated and 1 saturated attached to glycerol)

Question 4

Which of the dietary lipids do not contain fatty acids

Answer 4

Cholesterol does not contain fatty acids

Triglycerides and phospholipids do contain fatty acids

Question 5

Where does lipids digestion occur?

Answer 5

In the small intestine

Question 6

almost all the fats in the diet, with the principal exception of a few short-chain fatty acids, are absorbed from the intestines into where?

Answer 6

Intestinal lymph

Question 7

Describe the action of pancreatic lipase and colipase

These enzyme require another molecule in order for them to work. What is it?

Answer 7

Their function is to breakdown triglycerides into 2 fatty acids and a monoglyceride.

Require bile salts

Question 8

Describe bile salts?

Answer 8

Synthesised by cholesterol in the liver

Secreted from the liver through the bile duct into the ampulla of Vater into the duodenum

Function is to emulsify fats to micelles i.e. turns large lipids droplets to smaller lipid droplets

Question 9

How does bile salts aid the pancreatic lipase function

Answer 9

It emulsifies fats into micelles (smaller fat droplets)

This increases the surface area of the droplet- allowing these enzymes to work more efficiently at breaking down the lipid.

Question 10

What is the mode of action of the drug Orlistat

Answer 10

It inhibits pancreatic lipases, the enzymes that break down triglycerides in the intestine.

Therefore, triglycerides from the diet are not hydrolyzed into absorbable free fatty acids, and instead are excreted unchanged.

Question 11

Describe how lipid are absorption by the body

Answer 11

During digestion, most triglycerides are split into monoglycerides and fatty acids.

These products pass through the enterocytes, where the monoglycerides and fatty acids are resynthesized into new molecules of triglycerides.

These new triglycerides are then packaged with cholesterol, lipoproteins and other lipids forming chylomicrons.

The chylomicrons are released by the enterocytes by exocytosis and enter the lymh.

Question 12

Describe the composition of chylomicrons

Answer 12

The chylomicrons are composed principally of triglycerides.

Contain about:

• 87% triglycerides
• 9% phospholipids
• 3% cholesterol
• 1% apoprotein B.

Question 13

Explain how chylomicron enters into the bloodstream?

Answer 13

The chylomicrons in lymph is transported upward through the thoracic duct and emptied into the circulating venous blood at the juncture of the jugular and subclavian veins.

This is how it enters the bloodstream

Question 14

Most of the chylomicrons are degraded as they pass through the capillaries of various tissues, particularly adipose and muscle tissue.

Describe how these tissues degrade the chylomicrons?

Answer 14

• These tissues synthesize the enzyme lipoprotein lipase, which is transported to the surface of capillary endothelial cells, where it hydrolyzes the triglycerides of chylomicrons as they come in contact with the endothelial wall, thus releasing fatty acids and glycerol
• The fatty acids released from the chylomicrons, diffuse into the fat cells of the adipose tissue and muscle cells. Once inside these cells, the fatty acids can be used for fuel or again synthesized into triglycerides

Question 15

After the triglycerides are removed from the chylomicrons, what has the chylomicron become?

Answer 15

Cholesterol-enriched chylomicron remnants

Question 16

Aside from the chylomicrons, which are very large lipoproteins, there are four major types of lipoproteins, classified by their densities.

Name the other four major types

Answer 16

1. very low density lipoproteins (VLDLs) - which contain high concentrations of triglycerides and moderate concentrations of both cholesterol and phospholipids
2. Intermediate-density lipoproteins (IDLs) - which are VLDLs from which a share of the triglycerides has been removed, so the concentrations of cholesterol and phospholipids are increased
3. Low-density lipoproteins (LDLs) - which are derived from IDLs by the removal of almost all the triglycerides, leaving an especially high concentration of cholesterol and a moderately high concentration of phospholipids
4. High-density lipoproteins (HDLs), - which contain a high concentration of protein (about 50 percent) but much smaller concentrations of cholesterol and phospholipids.

Question 17

Describe the endogenous lipid transport

Answer 17

• The endogenous pathway involves the liver synthesizing lipoproteins.
• TG and cholesterol ester are generated by the liver and packaged into VLDL particle, which are released into the circulation.
• VLDL is then processed by lipoprotein lipase (LPL) in tissues to release fatty acids and glycerol.
• The fatty acids are taken up by muscle cells for energy or by the adipose cells for storage.
• Once processed by LPL, the VLDL becomes IDL, a smaller, denser lipoprotein than VLDL. The fate of some of the IDL particles requires them to be reabsorbed by the liver (by the LDL receptor); however, other IDL particles are hydrolyzed in the liver by hepatic-triglyceride lipase to form LDL, a smaller, denser particle than IDL.
• LDL is the main carrier of circulating cholesterol within the body
• LDL can either be taken up by the LDL receptor on the liver or used by extra-hepatic cells for cell membrane and steroid hormone synthesis.

Question 18

What happens to the chylomicron remnant

Answer 18

Chylomicron remnant particles are removed from the plasma by way of chylomicron remnant receptors present on the liver.

Question 19

What is the order of lipoproteins in the endogenous lipid transport

A) Intermediate density lipoprotein (IDL)

B) Low density lipoprotein (LDL)

C) Very low density lipoprotioen (VLDL)

Answer 19

C) Very low density lipoprotioen (VLDL)

A) Intermediate density lipoprotein (IDL)

B) Low density lipoprotein (LDL)

Question 20

Name a few processes plasma triglycermide is important in

Answer 20

Phospholipid synthesis

Beta oxidation

Ketone bodies production

Question 21

What must fatty acids be bound to in blood and why?

Answer 21

Must be bound to albumin as they act as a detergent

Question 22

Define the process beta oxidation

Answer 22

Catabolic process by which fatty acid molecules are broken down in the mitochondria to generate acetyl-CoA, FADH₂ and NADH

Question 23

Before the fatty acids can be used for energy, they must be processed further by which cellular structure?

Answer 23

The mitochondria

Question 24

What happens to the glycerol when triglyceride are metabolised

Answer 24

Glycerol, upon entering the active tissue, is immediately changed by intracellular enzymes into glycerol-3-phosphate, which enters the glycolytic pathway for glucose breakdown and is thus used for energy

Question 25

Where does beta oxidation occur?

Answer 25

In the mitochondria

Question 26

In order for fatty acids to undergo beta oxidation they must first cross the mitochondrial membranes. How does it do this?

Answer 26

This carrier-mediated process uses **carnitine** as the carrier substance _Carnitine palmitoyl transferase 1 (CPT1)_: swaps carnitine for fatty acyl-coA. Moving them through the outer mitochondrial membrane. Forms fatty acid carnitine and coA. _Carnitine palmitoyl transferase 2 (CPT2):_ Deoes the opposite. Swaps fatty acid carnitine for coA- forming carnitine and fatty acyl-coA. Moving them through the inner mitochondrial membrane. Fatty acyl-coA is now in the mitochondria

Question 27

When fatty acids first enter a cell it must be added to acetyl coA to form \_\_\_. Why is this important?

Answer 27

Forms fatty acyl-CoA Important as it prevents the fatty acids from having its detergent function

Question 28

Describe the beta oxidation pathway

Answer 28

* Fatty acyl-coA are degraded by oxidation at the beta carbon. * Occurs in the mitchondria * Occur in rounds, which each round reducing the size of the fatty acyl chain by 2 carbons. * Each round produces: 1 FADH2, NADH and acetyl coA. * Eventually, after multiple rounds, ends up with a final acetyl coA * Acetyl coA can be further oxidised to yield ATP.

Question 29

Lipoprotein Lipase (LPL) hydrolyses triglycerides in chylomicrons- allowing the free fatty acids to be taken up by the cell. 1. Which enzyme inside the cell re-esterifies them back to triglyceride? 2. Where does the glycerol come from that allows the triglyceride to be reformed?

Answer 29

1. Diacylglycerol Acyl Transferase (DGAT) 2. The glycerol is obtained from glycolysis (DHAP).

Question 30

Describe the lipolysis process

Answer 30

* This is the breakdown of triglycerides into glycerol and 3 fatty acids. Important in the formation of ATP. * Triglycerides are broken down by **hormone** **sensitive** **lipase** located in adipose tissue. * Hormone-sensitive lipase is activated by cAMP-dependent phosphorylation in response to adrenaline in fasted state, inhibited by insulin * Free fatty acid needs to be bound to albumin and is transported to the muscle that requires ATP. * Glycerol is transported to the liver to be used in the glucose metabolism pathway.

Question 31

•Fatty acids are built ___ carbons at a time. Limited to ____ carbons?

Answer 31

A) 2 carbons B) 16 carbons

Question 32

What are the enzymes that are important in the lipolysis process?

Answer 32

Hormone sensitive lipase

Question 33

What are the enzymes that are important in the fatty acid synthesis

Answer 33

Acetyl CoA Carboxylase Fatty acid synthase

Question 34

What are the enzymes that are important in the triglyceride synthesis

Answer 34

Lipoprotein lipase (LPL) Diacylglycerol acyl transferase (DGAT)

Question 35

What are the enzymes that are important in the lipid digestion

Answer 35

Pancreatic lipase and colipase

Question 36

Describe the process of fatty acid synthesis

Answer 36

Formed from acetyl CoA Acetyl CoA is converted to malonyl coA by acetyl coA carboxylase. Malonyl coA through multiple steps (by fatty acid synthase) formed fatty acids.

Question 37

Where in the cell does fatty acid synthesis occur?

Answer 37

In the cytoplasm

Question 38

Both acetyl coA carboxylase and fatty acid synthase require an additional molecule in order to function in the fatty acid synthesis. What is this additional molecule for acetyl coA carboxylase

Answer 38

The vitamin, biotin

Question 39

Both acetyl coA carboxylase and fatty acid synthase require an additional molecule in order to function in the fatty acid synthesis. What is this additional molecule for fatty acid synthase?

Answer 39

NADPH

Question 40

What is the functions of malonyl CoA?

Answer 40

1. Can be converted by multiple steps to fatty acids 2. **Inhibits** **fatty** **acid** **oxidation** - acts as a switch so you don't synthesis and breakdown fatty acids at the same time

Question 41

Describe how ketone bodies are found?

Answer 41

* Beta oxidation leads to a large amount of acetyl CoA being produced * This acetyl CoA is added to OAA to form citrate which can enter the TCA cycle and form ATP. * However, if OAA is not present, can be because of the high level of acetyl CoA being formed, then the acetyl CoA does not go through the TCA. It will then be converted to ketones. * Therefore, **Ketone body formation is an “overflow” pathway for acetyl CoA use**

Question 42

Why does the body make ketone bodies?

Answer 42

The body does not want to waste the acetyl coA as it can be used by some cells as fuel

Question 43

Why is ketone body formation a key characteristic of unregulated diabetes?

Answer 43

In diabetes, fatty acid oxidation all the time (as the cells cannot take up the high glucose level in the blood so they start to produce their own fuel- the cells think they are starved). Therefore, lipolysis occurs, resulting in high levels of acetyl CoA formation. There is so much acetyl CoA being formed, that some are used to form ketones. High level of ketones are being used that the cells cannot use them all as fuel so they remain in the blood and eventually acidify the blood- leading to ketoacidosis

Question 44

Describe essential fatty acids

Answer 44

These are the fatty acids that cannot be synthesised and are obtained only from the diet. e.g. omega 6 and omega 3 fatty acids

Question 45

Why are essential fatty acids so important?

Answer 45

Their functions include: * Cell Membrane Formation * Required for proper growth & development * Required for brain & nerve function * Precursors for molecules that are important in the inflammatory response

Question 46

Name the key hormonal regulation of lipid metabolism?

Answer 46

**Insulin**:​ * Stimulates FA synthesis, TAG synthesis * Suppresses Lipolysis **(Nor)adrenaline**: * Stimulates Lipolysis

Question 47

Describe the effect of insulin of lipid metabolism

Answer 47

* GLUT4-mediated transport of glucose * Increases acetyl-coA carboxylase activity * Increases expression of fatty acid synthase * Increases activity of Lipoprotein lipase (in adipose)

Question 48

Describe the effect of nor(adrenaline) of lipid metabolism

Answer 48

* cAMP synthesis * cAMP-dependent protein kinase (PKA) activation * PKA-mediated phosphorylation and activation of HSL

Question 49

Nor(adrenaline) effects the lipid metabolise during which state (fasted or fed)?

Answer 49

Fasted state

Question 50

Insulin effects the lipid metabolise during which state (fasted or fed)?

Answer 50

Fed state