6 Lipid Metabolism

Question 1

Q: What’s the general structure for a fatty acid?

Answer 1

A: hydrophilic carboxylic head and hydrophobic hydrocarbon tail

Question 2

Q: What’s a saturated fatty acid? (3)

Answer 2

A: completed saturated with H
No double bonds
Completely straight

Question 3

Q: What’s does an unsaturated fatty acid contain? Shape?

Answer 3

A: double bond

Db inhibits rotation around the bond = kink in chain

Question 4

Q: What form are fatty acids stored in?

Answer 4

A: triacylglycerols (triglycerides)

Question 5

Q: Which cells in mammals are specialised for fat storage?

Answer 5

A: adipocytes

Question 6

Q: Which is solid and which is liquid?

Saturated fatty acids
Unsaturated

Answer 6

A: solids, liquids

Question 7

Q: What are the 3 main sources of fats?

Answer 7

A: diet, de novo biosynthesis in liver, adipocytes storage (hydrolysed to give fatty acids and glycerol)

Question 8

Q: What is the role of bile salts? Generated? Stored? Release?

Answer 8

A: emulsify fats and aid absorption-> Interacts with solute and triacylglycerides due to hydrophobic and hydrophilic ends
Get them into soluble form

Generated in liver
Stored in gal bladder
Secreted into small intestine during digestion

Question 9

Q: What’s a mixed micelle? (8)

Answer 9

A: mixture of triacyl, diacyl, monoacylglycerols and free fatty acids WITH bile salts, cholesterol, lysophosphatidic acid, fat soluble vitamins

Question 10

Q: What occurs to mixed micelles after formation? (4)

Answer 10

A: absorbed by enterocytes and triacylglycerols TAGs are resynthesised
TAGs are packed into chylomicrons which enter lymphatic system and join circulatory system

Question 11

Q: How does the caloric yield of fatty acids differ to that of carbohydrates?

Answer 11

A: FA is double that of carbs

Question 12

Q: What’s the process of fat metabolism and where does it occur? What does it result in?

Answer 12

A: beta oxidation, mitochondria (outer membrane), acetyl CoA

Question 13

Q: Summarise the process of beta oxidation using a general equation. Enzyme? What does the reaction use? (2)

Answer 13

A: FA + ATP + HS-CoA -> acyl-CoA + AMP + PPi
E: acyl CoA synthetase

ATP -> AMP
2 high energy bonds used
2 phosphoanhydride bonds used

Question 14

Q: What is the general formula for acyl CoA?

Answer 14

A: O
II
R— C — S —CoA

Question 15

Q: How do you move acyl CoA into the mitochondria? Draw a diagram.

Answer 15

A: carnitine shuttle

3 components

• CPTI
• CPTII
• translocase

Question 16

Q: What occurs in the beta oxidation cycle? Draw a diagram.

Answer 16

A: “Fatty acids are firstly converted within the mitrochondrial matrix into an acyl CoA species via the enzyme Acyl CoA synthetase which requires ATP hydrolysis”

1 fatty acyl CoA is oxidised and FAD reduced to FADH2
2 molecule produced is hydrolysed
E: 3 hydroxyacyl CoA hydrolase
3 product is oxidised and NAD is reduced to form NADH
E: L-3-hydroxyacyl CoA dehydrogenase
4 molecule of acetyl CoA is kicked off by bringing in molecule of CoA
E: beta ketothiolase

Fatty acyl CoA as a result has been shortened by 2 carbons and cycle repeats

Question 17

Q: What first occurs during the beta oxidation of palmitic acid? What’s the overall equation? Final cycle?

Answer 17

A: first E: acyl CoA synthetase converts into 16 C palmitoyl CoA

Palmitoyl CoA + 7FAD + 7 NAD+ + 7H2O + 7CoA -> 8 acetyl CoA + 7FADH2 +7NADH

On the final cycle (4C fatty acyl CoA intermediate enters cycle) 2 acetyl CoA molecules are produced

Question 18

Q: What is palmitic acid?

Answer 18

A: saturated fatty acid

Question 19

Q: How does acetyl CoA enter aerobic respiration and under what circumstances? Why?

Answer 19

A: TCA cycle but only if beta oxidation and carbohydrate metabolism are balanced, oxaloacetate is needed for acetyl CoA entry into the TCA cycle

Question 20

Q: What occurs if fat breakdown predominates carbohydrate metabolism?

Answer 20

A: acetyl CoA forms

Question 21

Q: Name 3 ketone bodies?

Answer 21

A: Acetoacetate
D-3-hydroxybutyrate
Acetone

Question 22

Q: What is the net ATP production of palmitate beta oxidation compared to aerobic respiration?

Answer 22

A: Palmitoyl CoA + 7FAD + 7 NAD+ + 7H2O + 7CoA -> 8 acetyl CoA + 7FADH2 +7NADH

7 cycles of beta oxidation = 35
8 a CoA = 96
NADH FAD —> 131

-2 ATP used in beginning = 129

Compared to 38

Much more ATP from fatty acid metabolism that glucose metabolism.

Question 23

Q: What is fatty acid synthesis called?

Describe the process? Involves? (2) Sequential action of? (3) Link?

Answer 23

A: liposynthesis

Decarboxylative condensation reactions involving the molecules Acetyl-CoA and Malonyl-CoA

After each round of elongation, the fatty acid undergoes reduction and dehydration by the sequential action of:
Ketoreducatase (KR)
Dehydratase (DH)
Enol Reductase (ER)

The growing fatty acyl group is linked to an acyl carrier protein (ACP).

Question 24

Q: What are the differences between fatty acid synthesis and fatty acid degradation? Type of reaction? Carriers? Reducing power?

Answer 24

A:
FAS= synthesis, FAD= beta oxidation
carriers: FAS= ACP, FAD= CoA
Reducing power: FAS= NADPH, FAD= FAD/NAD

Question 25

Q: Summary equation for lipogenisis for palmitate.

Answer 25

A: acetyl CoA (C2) + 7 malonyl CoA (C3) + 14 NADPH + 14H+ -> palmitate (C16) + 7CO2 + 6H2O + 8CoA-SH + 14NADP+

Question 26

Q: Where does fatty acid synthesis occur?

Answer 26

A: cytoplasm

Question 27

Q: Where does fatty acid degradation occur?

Answer 27

A: mitochondria

Question 28

Q: What does the desaturation of fatty acids require?

Answer 28

A: E action: fatty acyl-CoA desaturases

Question 29

Q: Recall 2 examples of inborn errors of lipid metabolism.

Answer 29

A: Medium-chain acyl-coenzyme A dehydrogenase deficiency (MCADD)

Primary carnitine deficiency

Question 30

Q: Disorders of fatty acid oxidation arise from mutations in which family of enzymes?

Answer 30

A: acyl-CoA dehydrogenases

Question 31

Q: MCADD. Inheritance? Test? What happens if they lose their appetite? Treatment?

Answer 31

A: Medium-chain acyl-coenzyme A dehydrogenase deficiency = in born error of lipid metabolism

Autosomal recessive
Part of heel prick test
Patients with loss of appetite may need IV glucose to ensure body isn’t dependent on FA for energy
If diagnosed. Need to avoid fasting and need to have a carbohydrate rich diet

Question 32

Q: What is the inheritance for primary carnitine deficiency? Treatment? What is carnitine needed for?

Answer 32

A: (in born error of lipid metabolism)

Autosomal recessive
Can get carnitine supplements as treatment
(Carnitine is needed to chaperone acyl group into mitochondrial matrix from the outer mito matrix)

Question 33

Q: Which 2 enzymes are needed in fatty acid synthesis?

Answer 33

A: Acetyl CoA Carboxylase, Fatty Acid Synthase (FAS)

Question 34

Q: What are the 7 steps for fatty acid synthesis? (palmitate)

Answer 34

A: 1 acetyl CoA -> Malonyl CoA (3C)
E: Acetyl CoA carboxylase
ATP, HCO3- in and ADP +Pi out

2 Transfer of Malonyl from Malonyl CoA to Acyl Carrier Protein (ACP) to form Malonyl-ACP
E: Malonyl-CoA-ACP Transferase

3 Transfer of acetyl from a CoA species to acyl carrier protien (ACP) to form Acetyl-ACP
E: Acetyl-CoA-ACP Transferase

4 Condensation of acetyl-ACP with malonyl-ACP to form 4C fatty acid species (FAS does this)
E: β-ketoacyl ACP synthase

5 Reduction of Acetoacetyl-ACP to D-3-hydroxybutyryl-ACP
E: β-ketoacyl ACP reductase

6 Dehydration to crotonyl ACP (a.k.a. trans-∆2-Enoyl-ACP
E: 3 hydroxyacyl-ACP dehydrase

7 Further reduction to butyryl-ACP
E: Enoyl-ACP reductase

The process cycles a further six times from step 4-7 to yield the 16C species palmitoyl-ACP, which is hydrolysed to give palmitate and ACPp