Lipids

Question 1

Lipid Structure Facts

Answer 1

• Structurally diverse
• Generally insoluble in water (hydrophobic)
• Most only contain C, H, O – (phospholipids contain P, N)
• More reduced than carbohydrates
  – release more energy when oxidised – complete oxidation requires more O2

Question 2

Structure of fatty acids

Answer 2

Alaphatic chain od methyl groups with acid (carboxylic) group on one end

Question 3

What are the types of lipids

Answer 3

Fatty acids, triacylglycerols and ketone bodies are the types of lipid used as fuel molecules.

Question 4

How are lipids stored

Answer 4

Triacylglycerol

Question 5

What is the structure of Triacylglycerol

Answer 5

Glycerol backbone attached to three fatty acids

Question 6

How are ketone bodies formed

Answer 6

In the liver fatty acids are turned in to ketone bodies
Derived from fatty acids

Question 7

What is derived from Fatty Acids

Answer 7

Fatty acids - Fuel molecules
Triacylglycerols (Triglycerides) - Fuel Storage and insulation
Phospholipids – components of membranes and plasma
lipoproteins
Eicosanoids – local mediators (signaling molecules)

Question 8

What is derived from Hydroxy-methyl-glutaric acid derivatives (C6 compound)

Answer 8

Kentone Bodies (C4) - Water soluble fuel molecules
Cholesterol (C27) – membranes (fluidity) and steroid hormone synthesis
Cholesterol esters – cholesterol storage
Bile acids and salts (C24) – lipid digestion

Question 9

What are the fat soluble vitamins

Answer 9

A, D, E and K.
derived from lipids

Question 10

Does Triacylglycerols Glycogen Muscle protein vary with heathy to obese people

Answer 10

Glycogen and Muscle protein remain constant

Triacylglycerols go up with from heathy to obese by the weight increase

Question 11

What is Triacylglycerols derived from

Answer 11

Glycerol and Fatty acids in an esterification reaction

Question 12

What is Lipolysis

Answer 12

Triacylglycerols turning back in to Glycerol and fatty acids

Question 13

Function of Triacylglycerols,
Is it hydrophobic or hydrophilic

Answer 13

• Triacylglycerols are hydrophobic
• Therefore stored in ananhydrous form
• Stored in specialised tissue– adipose tissue
• Utilised in prolonged exercise, ‘starvation’,
  and also during pregnancy
• Storage/ mobilisation is under tight hormonal control

Question 14

what is the benefit of Tricylglyerols being hydrophobic

Answer 14

As its in an Anhydrous form
When stored they can hold alot more fuel per gram of weight

Question 15

When and where does Metabolism of triacylglycerols occur

Answer 15

• Stage 1
• GI Tract (lumen) (Small interstine)
• Extracellular

Question 16

What happens to fatty acids after metabolism of triacylglycerols (in to fatty acids and Glycerol)

Answer 16

• Converted back to triglycerides in G.I. tract in the cells
• Packaged into lipoprotein particle ( this stabilises them as they interact with many other pathways eg, amino acid pathway)
• The packages are called CHYLOMICRONS
• Released into circulation via lymphatics
• Carried to adipose tissue
• Stored as triglyceride (triacylglycerols)
• Released as fatty acids when needed
• Carried to tissues as albumin-fatty acid complex ( different transport process as lipids aren’t water soluble)

Question 17

What is the colour when you disect the lymphatics

Answer 17

Looks milky due to the CHYLOMICRONS

Question 18

Fatty Acid Catabolism - Summary

Answer 18

1. FA is activated (by linking to coenzyme A outside the mitochondrion)
2. Transported across the inner mitochondrial membrane using a carnitine shuttle
3. FA cycles through sequences of oxidative reactions, with C2 removed each cycle

(C18 —> C16 + C2)

Question 19

How is fatty acid Activated

Answer 19

Occurs outside the mitochondria, in cytoplasm

• Fatty acids activated by linking to coenzyme A
  (via high energy bond) by the action of fatty acyl CoA synthase :

CH3(CH2)nCOOH (FATTY ACID) + ATP + CoA —> CH3(CH2)nCO~CoA (fatty acyl~CoA) + AMP + 2Pi

Question 20

How are fatty acyl~CoA transported

Answer 20

Activated fatty acids (fatty acyl~CoA) do not readily cross the inner mitochondrial membrane
thus
Carnitine shuttle transports fatty acyl~CoA across the mitochondrial membrane

Question 21

How does the Carnitine Shuttle work

Answer 21

1. Acyl Coa is put on to the carnitine making it Acl Carnitine using Carnitine acyltransferases 1
2. Carnitie shuttle swaps Acyl carnitine for carnitine across membrane
3. Acyl transferred back on to the CoA again using
   Carnitine acyltransferases 2

Question 22

What does Carnitine acyltransferases do

Answer 22

Puts Acyl group onto Carnitine and helps move it across membrane

Question 23

How is Carnitine shuttle transport regulated

Answer 23

• Regulated (AMP, insulin), so controls the rate of FA oxidation
• CAT1 inhibited by malonyl~CoA (biosynthetic intermediate)
• Defects can occur in this transport system (exercise intolerance, lipid droplets in muscle)

Question 24

Why is called Beta - Oxidation

Answer 24

As its the Beta Carbon that gets oxidised

Question 25

What is the final step of B-oxidation

Answer 25

CO.CH2.CO-CoA gets cleaved and and addition of CoA to form CO-CoA + CH3.CO-CoA

Question 26

What is ultimately produced by B-oxidation and what are they used for

Answer 26

β-oxidation ultimately generates acetyl CoA and reducing power. These intermediates are used to generate ATP in stages 3 and 4 of catabolism

Question 27

Where does B-Oxidation occur

Answer 27

Most tissues and white blood cells DOESNT OCCUR IN BRAIN as fatty acids can't get though brain barrier Doesn't occur in RBC as there is no mitochondria

Question 28

Fatty acid and glycerol metabolism (B-oxidation) (8) - Key Points

Answer 28

* Mitochondrial * Cycle of reactions * Removal of 2C units per cycle * β-carbon oxidation * H+ and e- transferred to NAD+ and FAD * Stops in absence of O2 * Regulated by AMP (insulin – liver) * No direct ATP synthesis

Question 29

What happens to glycerol

Answer 29

Glycerol can be transported in the blood to the liver, where it is metabolised By Glycerol kinase using ATP forming Glycerol phosphate

Question 30

What happens to Glycerol phosphate

Answer 30

There are two pathways It can enter glycolysis, using glycerol 3-phosphate dehydrogenase It will create Dihydroxyacetone - P or It can be stored as Fat (triacylglycerol) This requires fatty acids

Question 31

Where and How ketone bodies generated

Answer 31

The liver mitochondria constantly generates ketone bodies from acetyl CoA Adipose tissue release fatty acids liver sensors pick this up Thus generates Ketone bodies Produced when Acetyl CoA is in excess

Question 32

When is the production of ketone bodies higher

Answer 32

Production is much higher during fasting (and starvation)

Question 33

What are Kentone bodies used for

Answer 33

* Used by peripheral tissues (muscle) * Alternative fuel to glucose (helps conserve glucose)

Question 34

Why is ketone bodies an important energy source

Answer 34

They are water soluble (whilst fatty acids are NOT thus finite amount of fatty acids can be transported) Thus provided more fuel molecules

Question 35

What is the pKA of kentones What is Physiological ketosis

Answer 35

acidic – pKa ~4 (deporotonated) making blood ph more acidic Blood becomes more acidic due to higher ketone conc

Question 36

What is the Normal Plasma ketone conc

Answer 36

Normal plasma ketone body concentration < 1 mM

Question 37

What is the Starvation, Ketones conc

Answer 37

Starvation 2-10 mM (physiological ketosis)

Question 38

What happens in untreated Type 1 diabetes

Answer 38

Untreated Type 1 diabetes > 10 mM (pathological ketosis)

Question 39

What are the steps in ketone production

Answer 39

1.Acetly CoA (CH3CO-CoA) is sythesised in to 2.Hydroxymethyl glutaryl-CoA. (HMG-CoA) which is lysed by the enzyme lyase in to 3. acetoacetate and β-hdroxybutyrate these are used as biological fuels

Question 40

What happens when Hydroxymethyl glutaryl-CoA. (HMG-CoA) interacts with HMG-CoA Reductase (staitin drug) When the insulin/glucagon ratio is high

Answer 40

Mevalonate ---> Cholesterol occurs when When the insulin/glucagon ratio is high, i.e. fed state: Lyase is inhibited+reductase activated --> cholesterol synthesis

Question 41

Control of Ketone body production in the liver

Answer 41

1.Triacyglycerols levels get high 2. Fatty acids levels thus rise 3. Low NAD+ substrate 4. High NADH 5. This inhibits the TCA cycle 6. Thus acetyl-CoA gets diverted to produce Ketone Bodies

Question 42

What happens to Acetoacetate

Answer 42

Acetoacetate - Acetone- Acetoacetate - (using Sunccinyl CoA) turns to Acetoacetyl CoA - Then another CoA added to form Acetyl CoA (x2)- which is used in the TCA cycle Which is used to generate ATP

Question 43

What happens when the insulin/glucagon ratio is Low

Answer 43

When the insulin/glucagon ratio is Low, i.e. starvation state: Lyase is activated + reductase inhibited  ketone body

Question 44

What happens in Starvation / Diabetes

Answer 44

Ketone bodies gets used preferably rather than glucose glucose only used by cells that need it eg brain Diabetes this is uncontrolled all systems switched on blood glucose is very high Ketone levels gets very high no insulin generated no brake mechanism Kentone lavels build up leads to Ketoacidosis / Ketosis Blood Ph becomes acidic Can damage brain Leads to coma and can even Die Given Insulin to bring all process back under control lowers glucose and ketone levels.

Question 45

What Is the role of Acetyl CoA in metabolism

Answer 45

Its main function is to deliver the acetyl group to the citric acid cycle (Krebs cycle) to be oxidized for energy production.