Metabolism S5 - Lipid transport and by-products of energy production

Question 1

Why are lipids associated with proteins in the blood?

Answer 1

They are insoluble in water

Question 2

What are the two methods of lipid transport in the blood?

Answer 2

Lipoproteins or albumin (less than 2%)

Question 3

Lipoprotein disorders are associated with what main clinically important disease?

Answer 3

Atherosclerosis

Question 4

What is the general structure of lipoproteins?

Answer 4

Hydrophilic surface coat - apoproteins, cholesterol and phospholipids

Hydrophobic core - TAGs, Cholesterol esters

Question 5

How is the structure of lipoproteins maintained?

Answer 5

LCAT convert cholesterol to cholesterol esters when core is removed to maintain shape

Question 6

What structural role do apoproteins play?

Answer 6

• Involved in packaging non-water soluble lipids into soluble form
• This is possible as they contain a hydrophobic region that interacts with the lipid molecule and hydrophilic region that interacts with water

Question 7

What functional role do apoproteins play?

Answer 7

• May be involved in activation of enzymes
• Recognition of cell surface receptors
• Transport of lipids

Question 8

What do chylomicrons transport and to which destination?

Answer 8

TAGs

Intestine to adipose tissue

Question 9

What do VLDLs transport and to which destination?

Answer 9

TAGs

Liver to adipose tissue

Question 10

What do LDLs transport and to which destination?

Answer 10

Cholesterol

Liver to tissue

Question 11

What do HDLs transport and to which destination?

Answer 11

Cholesterol

Tissues to the liver

Question 12

All cells (except red blood cells) are able to synthesise _______ from acetyl CoA and could satisfy their requirements by biosynthesis. In practice, all cells appear to prefer the uptake of ________ ________ circulating in plasma _________

Answer 12

Cholesterol

Pre-formed cholesterol

Lipoproteins

Question 13

Tissues obtain the _______ they need from LDLs by the process of _______ ________ _______. LDL particles are taken up by the cell and the cholesterol released inside the cell

Answer 13

Cholesterol

Receptor mediated endocytosis

Question 14

Outline receptor mediated endocytosis of cholesterol

Answer 14

• Cells requiring cholesterol synthesise LDL receptors that are exposed on the cell surface
• These receptors recognise and bind specific apoproteins (Apo B100) on the surface of the LDL
• The LDL receptor with its bound LDL is then endocytose by the cell and subjected to lysosomal digestion
• Cholesterol can be stored (as cholesterol esters) or used by the cell
• This also inhibits the synthesis of cholesterol by the cell and reduces the synthesis and exposure of LDL receptors.
• This prevents the cell from accumulating too much cholesterol

Question 15

Describe Type III hyperlipoproteinaemia

Answer 15

• Raised LDL and chylomicron remnants
• Associated with coronary artery disease
• Caused by defective apoprotein E

Question 16

Describe Type IV hyperlipoproteinaemia

Answer 16

• Raised VLDLs
• Associated with coronary artery disease
• Defect unknown

Question 17

Describe Type V hyperlipoproteinaemia

Answer 17

• Raised chylomicrons and VLDL in fasting plasma
• Associated with coronary heart disease
• Defect unknown

Question 18

What type hyperlipoproteinaemia is familial cholesterolaemia

Answer 18

IIa

Question 19

List some treatments for hyperlipoproteinaemia

Answer 19

• Reduce cholesterol and TAGs in the diet
• Statins: inhibits HMG-CoA reductase to prevent cholesterol synthesis from acetyl-CoA
• Bile Salt sequestrants: lower cholesterol by increasing its disposal from the body. They bind to the GI tract preventing them from being reabsorbed into the hepatic-portal circulation and promoting their loss in faeces

Question 20

Describe two mechanisms by which tissues can obtain lipids from lipoproteins

Answer 20

1) Lipoprotein lipase - Removes core TAGs from lipoproteins to produce fatty acids and glycerol, found attached to inner surface of capillaries in adipose tissue
2) Receptor mediated endocytosis - LDL binds to LDL receptors on surface membrane and complex is taken up in cell

Question 21

How are superoxide radicals produced in the cell?

Answer 21

0.1-2% of electrons are leaked from the electron transport chain before they reach the end of the chain and prematurely reduce oxygen in the mitochondria

Question 22

List 3 reactive oxygen species

Answer 22

1) Hydroxyl radical
2) Nitric oxide
3) Peroxynitrite (formed from nitric oxide and oxygen reacting together

Question 23

Which ROS has an important role in inflammation/

Answer 23

Peroxynitrite

Question 24

Outline cellular defences against ROS

Answer 24

• Superoxide dismutase + catalase
• NADPH and glutathione
• Antioxidant vitamins
• Flavonoids and vitamins

Question 25

How is superoxide dismutase used as a cellular defence against ROS?

Answer 25

- SOD catalyses the reaction of superoxide radicals together to form water + hydrogen peroxide - However hydrogen peroxide os a ROS - Catalase rapidly breaks hydrogen peroxide down to water and oxygen

Question 26

The reaction of unsaturated lipids with ROS forms ______ ______. This damage to cell membranes is thought to be involved in the early stage of cardiovascular disease.

Answer 26

lipid peroxides

Question 27

What is hyperlipoproteinaemia?

Answer 27

Any condition in which, after a 12 hour fast, the plasma cholesterol and/or plasma triglycerides are raised

Question 28

List signs or symptoms of very high blood cholesterol

Answer 28

- Corneal arcus - Xanthelasma and/or tendon xanthoma - Accelerated development of atherosclerotic diseases

Question 29

Outline two pathways by which tissues can obtain the cholesterol they need

Answer 29

1) Direct synthesis of cholesterol from acetyl CoA within tissues 2) Receptor mediated endocytosis of LDL particles

Question 30

What cells are capable of oxidative burst?

Answer 30

Neutrophils and monocytes

Question 31

Name two enzymes involved in defences against ROS

Answer 31

Superoxide dismutase Catalase

Question 32

What is oxidative stress?

Answer 32

- Occurs when the production of ROS is excessive and anti-oxidant levels are low - Underlies pathology of atherosclerosis, Parkinson's and Alzheimers's

Question 33

What are the potential problems of a low-fat diet?

Answer 33

Need fats for cellular components such as lipid membranes as well as signalling molecules

Question 34

Name two anti-oxidant vitamnins

Answer 34

Vitamin E | Vitamin C

Question 35

Briefly explain how a respiratory burst is produced by monocytes and neutrophils

Answer 35

- Produced by a membrane-bound enzyme complex termed NADPH oxidase - It transfers electrons from NADPH across the membrane to couple these to molecular oxygen to generate superoxide radicals