Fatty Acid Production and Oxidation

Question 1

Name the 3 main sites of lipogenesis

Answer 1

Liver, white adipose tissue and lactating mammary glands

Question 2

Name the type of transport shuttle that is involved in lipogenesis

Answer 2

Carnitine shuttle

Question 3

Name the type of transport shuttle that is involved in lipolysis

Answer 3

Citrate shuttle

Question 4

What is malonyl-CoA and how does it affect lipolysis?

Answer 4

malonyl-CoA is an intermediate in the mechanism of fatty acid synthesis (lipogenesis) and it works to inhibit the carnitine shuttle of lipolysis to prevent newly formed fatty acids from being oxidised in the mitochondriia

Question 5

What is the role of acetyl CoA carboxylase in lipogenesis?

Answer 5

Conversion of acetyl CoA to malonyl CoA

Question 6

Describe how acetyl CoA carboxylase can be modified by polymerisation

Answer 6

Enzyme is activated when in polymerised, and inactive when not. Citrate activates this enzyme by promoting polymerisation (as a lot of citrate indicates a lot of glucose which may need conversion to fatty acids). Conversely, the enzyme is inhibited by the final product of fatty acid synthesis (palmitoyl-CoA) which causes depolymerisation of filaments.

Question 7

Describe how acetyl CoA carboxylase can be modified by hormone-dependent phosphorylation

Answer 7

Glucagon activates cAMP-dependent protein kinase which phosphorylates enzyme and inactivates it. Insulin promotes dephosphorylation to activate enzyme and lipid synthesis.

Question 8

Name the three ways in which acetyl CoA carboxylase activity can be modified

Answer 8

polymerisation, phosphorylation and long-term genetic control

Question 9

Why is lipolysis necessary?

Answer 9

Carbohydrate stores can only provide short-term energy buffering, and other sources required in long-term starvation (e.g. lipids and ketone bodies)

Question 10

What is the initial substrate of lipolysis?

Answer 10

Triacylglycerol (TAG)

Question 11

What are the two products of lipolysis?

Answer 11

Glycerol and 3 free fatty acids

Question 12

Describe what happens to the free fatty acids formed from lipolysis

Answer 12

can be oxidised for energy (in muscle/liver - oxidative tissues) to form acetyl CoA (enters TCA cycle) in addition to many molecules of FADH2 and NADH which enter ETC. Fatty acids could also be converted to ketone bodies in liver for use in non-oxidative tissues (brain and erythrocytes)

Question 13

Describe what happens to the glycerol formed in lipolysis

Answer 13

Can be use for glucose synthesis in liver or phosphorylated to form PEP to be used in glycolysis or gluconeogenesis

Question 14

What is the role of the hormone-sensitive lipase in lipolysis?

Answer 14

Converts triacylglycerol into glycerol and 3 free fatty acids

Question 15

Describe how the hormone-sensitive lipase enzyme is regulated

Answer 15

Sensitive to cAMP levels (which respond to hormone signals). Glucagon/adrenaline stimulates enzyme to encourage glycerol and FFA production. Insulin inhibits the enzyme in order to inhibit further production of glucose as it’s not required.

Question 16

Describe the process of fatty acid activation in lipolysis

Answer 16

In liver/muscle cells: outer mitochondrial membrane facilitates free fatty acids to combine with CoA in presence of thiokinase to produce activated acyl CoA

Question 17

Describe the carnitine shuttle in lipolysis

Answer 17

acyl CoA attaches to carnitine and loses CoA group in the presence of CPT-I. Fatty acyl-carnitine is formed and transported across membrane into mitochondrial matrix by translocase enzyme. Fatty acyl group transferred back to CoA (fatty acyl carnitine + CoA -> carnitine + fatty acyl CoA) using enzyme CPT-II. Carnitine is then returned to outer mitochondrial membrane to exchange for another molecule of fatty acyl-carnitine

Question 18

What is meant by the ‘carnitine shuttle’?

Answer 18

CPT-I, CPT-II and translocase enzymes involved in the transport of acyl CoA into the mitochondrial matrix in fatty acid breakdown

Question 19

What is malonyl-CoA?

Answer 19

Compound formed in fatty acid synthesis

Question 20

Describe three ways in which the activity of the CPT-I enzyme (in the carnitine shuttle) can be modulated

Answer 20

Stimulated by glucagon (via cAMP), regulated transcriptionally with activity rising in extended fasting and diabetes (to increase fatty acid oxidation) and malonyl-CoA inhibits enzyme to prevent newly formed fatty acids from being oxidised immediately in the mitochondrial matrix

Question 21

Which two types of cell cannot undergo beta-oxidation of fatty acids, and why?

Answer 21

Brain cells and erythrocytes as they do not have mitochondria

Question 22

How to we obtain energy from fatty acids?

Answer 22

through beta oxidation; this involves oxidation by acetyl CoA dehydrogenases in the mitochondrial matrix

Question 23

What are the products of beta oxidation of fatty acids?

Answer 23

NAD, FADH2 and acetyl-CoA. The first two will enter the ETC directly to release energy, whereas the acetyl CoA will enter the TCA cycle to release energy.

Question 24

Define ‘ketogenesis’

Answer 24

The formation of ketone bodies from acetyl CoA (produced from the beta oxidation of fatty acids)

Question 25

Where does ketogenesis occur?

Answer 25

Mitochondria of liver cells

Question 26

Name the 4 enzymes involved in ketogenesis

Answer 26

acetoacetyl CoA thiolase, HMG-CoA synthase, HMG-CoA lyase, 3-hydroxybutyrate dehydrogenase

Question 27

Describe the mechanism of ketogenesis

Answer 27

1) Two acetyl CoA molecules (from B-oxidation of fatty acids) converted to acetoacetyl CoA via acetoacetyl CoA thiolase enzyme.
2) This molecule is then converted to HMG-CoA in presence of HMG-CoA synthase enzyme
3) HMG-CoA converted to acetoacetate in presence of HMG-CoA lyase enzyme
4) Acetoacetate split into two types; spontaneous reaction forms acetone in decarboxylation reaction, or 3-hydroxybutyrate is formed in the presence of a dehydrogenase enzyme

Question 28

How does acetylation affect the HMG-synthase enzyme?

Answer 28

acetylation deactivates enzyme

Question 29

Name the 3 main structures where ketone bodies are utilised

Answer 29

Heart (preferentially over glucose), brain and muscle

Question 30

How does the brain respond to starvation metabolically?

Answer 30

Instead of using 100% glucose, begins to use 50% ketone bodies to conserve glucose when glycogen stores are low

Question 31

Why can’t the liver oxidise ketone bodies?

Answer 31

Does not have the 3-ketoacetyl CoA transferase enzyme and therefore it cannot activate the acetoacetate in the oxidative pathway

Question 32

Describe the effects of excessive ketone body production

Answer 32

If formation far greater than use, hydrogen ions will accumulate leading to ketoacidosis as this exceeds buffering capacity of blood.

Question 33

Why are individuals with uncontrolled diabetes at risk of ketoacidosis?

Answer 33

Insulin normally inhibits ketone body production

Question 34

How does the oxidation of glucose affect the oxidation of lipid?

Answer 34

If there is high glucose, then the levels of citrate will rise as a lot of aerobic respiration will be occurring; this citrate will be converted to malonyl-CoA which will go on to inhibit the carnitine shuttle of fatty acid oxidation, and therefore high glucose levels inhibit fatty acid breakdown when it’s not necessary