6. Lipid Metabolism

Question 1

Structure of saturated fatty acids

Answer 1

completely saturated with hydrogen.
No double bonds.
Completely straight.
Solids

Question 2

Structure of unsaturated fatty acids

Answer 2

Double bond inhibits rotation around the bond
= kink in chain.
Liquids

Question 3

How are fatty acids often stored in cells?

Answer 3

As Triacylglycerols (triglycerides).

Question 4

What cells are specialised for fatty acid storage?

Answer 4

Adipocytes

Question 5

When are fatty acids in adipocytes used to provide energy?

Answer 5

In times of starvation

Question 6

3 Primary sources of fat

Answer 6

Diet
De novo biosynthesis (liver)
Storage depots in adipocytes

Question 7

What are triacylglyceriols hydrolysed to form?

Answer 7

Free fatty acids

Glycerol

Question 8

What is a good carrier of free fatty acids?

Answer 8

Albumin

Question 9

Where are bile salts generated and stored?

Answer 9

Generated in Liver

Stored in Gallbladder

Question 10

Where do bile salts pass during digestion and what do they do?

Answer 10

From bile duct into intestine

Emulsify fats in intestine, aiding digestion and absorption of fats and fat-soluble vitamins (A, D, E, K)

Question 11

What do bile salts have and what happens when they form micelles?

Answer 11

Hydrophobic face and a hydrophilic face.
When they form micelles, their hydrophilic faces face away from triacylglycerols (TAGs) and their hydrophobic faces point towards TAGs.

Question 12

What does a lack of bile salts result in?

Answer 12

Passage of fat through the gut undigested and unabsorbed causing steatorrhea (fatty stool).

Question 13

What is a mixed micelle?

Answer 13

A mixture of triacyl-, diacyl-, monoacylglycerols and free fatty acids with Bile Salts, Cholesterol, Lysophosphatidic Acid and fat soluble vitamins

Question 14

What does digestion of lipids by lipase form?

Answer 14

Monoacylglycerols (MAG), diacylglycerols (DAG) and free fatty acids (FAs)

Question 15

Where are mixed micelles absorbed and what happens?

Answer 15

By enterocytes in small intestine
Triacylglycerol reformed
Modified into chylomicrons
Enter lymphatic system

Question 16

Orlistat

Answer 16

Lipase inhibitor
Reduces fat absorption by 30% which is excreted via faecal route
Treats obesity

Question 17

What are the side effects of orlistat?

Answer 17

Abdominal pain
Urgency to defecate
Steatorrhea

Question 18

Where does >50% of the body’s energy needs (except brain) come from?

Answer 18

Oxidation of fatty acids

Question 19

Caloric yield of fatty acids relative to carbohydrates

Answer 19

Fatty acids caloric yield 2X that of carbohydrates

Question 20

Where does Beta- Oxidation occur?

Answer 20

Mitochondria

Question 21

What does Beta-Oxidation result in formation of?

Answer 21

Acetyl CoA

Question 22

Describe beta oxidation

Answer 22

Fatty acid to acyl coA: Using 2 ATPs in outer mitochondrial membrane
Enter mitochondria by carnitine shuttle
Fatty acyl coA: oxidised and gives off FADH2
Molecule produced hydrolysed
This is then Oxidised and gives off NADH
Acetyl coA is produced by adding CoA using B KETOTHIOLASE

Question 23

What happens to the remaining fatty acyl CoA that has been shortened by 2C at the end of the Beta oxidation cycle?

Answer 23

It repeats the cycle

Question 24

What are the products of the Beta oxidation cycle?

Answer 24

1 molecule of acetyl CoA

1 acyl CoA species which is 2 carbons shorter than the original.

Question 25

Carnitine shuttle

Answer 25

Transports Acyl CoA into mitochondrial matrix by coupling it with carnitine to form Acyl carnitine

Question 26

How are carnitine and acyl carnitine moved to and from the mitochondrial matrix?

Answer 26

By a translocase

Question 27

Overall equation for breakdown of palmitate

Answer 27

Palmitoyl coA + 7FAD + 7 NAD+ + 7H20 + 7CoA ——> 8 acetyl coA + 7 FADH2 + 7 NADH

Question 28

When can acetyl coA from beta oxidation enter TCA?

Answer 28

When beta oxidation and carbohydrate metabolism are balanced as oxaloacetate is needed

Question 29

What happens if fat breakdown predominates (when fasting/ starving)?

Answer 29

Acetyl CoA forms ketone bodies e.g. Acetoacetate D-3-hydroxybutyrate Acetone

Question 30

Which 2 enzymes are involved in biosynthesis of lipids?

Answer 30

Acetyl CoA carboxylase | Fatty acid synthase (FAS)

Question 31

How often and how are fatty acids formed?

Answer 31

Sequentially by decarboxylative condensation reactions involving Acetyl-CoA and Malonyl-CoA

Question 32

What happens to fatty acids following each round of elongation?

Answer 32

Undergoes reduction and dehydration by the sequential action of a ketoreductase (KR), dehydratase (DH), & enol reductase (ER) activity

Question 33

What is the growing fatty acyl group linked to and what does this provide?

Answer 33

An acyl carrier protein (ACP) ACP provides a swinging arm mechanism to move the fatty acid chain from 1 domain to another, analogous to that of pyruvate dehydrogenase complex

Question 34

The process of lipogenesis is cycled a further 6 times from step 4-7 to yield

Answer 34

16C species: Palmitoyl-ACP | which is hydrolysed to give Palmitate and ACP

Question 35

Differences between fat metabolism and synthesis

Answer 35

``` Synthesis = ACP carrier NADP as reducing agent, Occurs in cytoplasm Metabolism = CoA carrier NAD+ and FAD as reducing agents Occurs in mitochondria ```

Question 36

Lipogenesis equation

Answer 36

Acetyl CoA + 7 malonyl CoA + 14 NADP + 14H+ = Palmitate + CO2 +6H2O + 8 CoA + 14 NADP+

Question 37

Why is there 1 fewer H2O than expected in the lipogenesis equation?

Answer 37

1 H2O is used in the hydrolysis of Palmitoyl ACP to form Palmitate and ACP

Question 38

Where does elongation of the acyl group to make fatty acids longer than 16C occur?

Answer 38

In mitochondria and endoplasmic reticulum

Question 39

What does desaturation of fatty acids require the action of?

Answer 39

Fatty acyl-CoA desaturases

Question 40

Acyl-CoA Dehydrogenases are a family of enzymes

Answer 40

There are different types of enzymes for the different lengths of fatty acid chain.

Question 41

What length of fatty acid chain is Medium-chain acyl-Co enzyme A dehydrogenase used for?

Answer 41

C6-C12

Question 42

What length of fatty acid chain is Long-chain acyl-Co enzyme A dehydrogenase used for?

Answer 42

C13-C21

Question 43

What type of disease is Medium-chain acyl-coenzyme A dehydrogenase deficiency (MCADD)?

Answer 43

Autosomal recessive

Question 44

When and why is MCADD screened for?

Answer 44

Heel prick test | If undiagnosed= fatal, sudden infant death syndrome

Question 45

What should patients with MCADD do?

Answer 45

Never go without food >12 hours | Adhere to high carbohydrate diet

Question 46

What type of disease is Primary Carnitine deficiency?

Answer 46

Autosomal recessive

Question 47

When do symptoms of Primary Carnitine deficiency arise?

Answer 47

During infancy/ childhood | Include encephalopathies

Question 48

What causes Primary Carnitine deficiency?

Answer 48

Mutations in SLC22A5 gene which encodes a carnitine transporter Results in reduced ability of cells to take up carnitine, needed for the β-oxidation of fatty acids.

Question 49

General structure of all fatty acids

Answer 49

``` Hydrophobic carbon tail Hydrophilic polar (charged) head ```