Lipid metabolism

Question 1

Fatty acid activation

Answer 1

Entrance into the mitochondrial matrix is highly regulated.
In order to cross the inner mitochondrial membrane where fatty acid oxidation occurs, fatty acids must be activated.

Question 2

Fatty acid activation

Initial step

Answer 2

The enzyme acyl-CoA synthetase catalyzes the formation of acyl-CoA from fatty acids and coenzyme A.

This reaction is energetically unfavorable and requires coupling to ATP hydrolysis.

Question 3

Fatty acid activation

Subsequent step

Answer 3

Acyl-CoA reacts with carnitine in the intermembrane space, forming acylcarnitine.

Acylcarnitine is recognized by inner mitochondrial membrane transport proteins and passes into the matrix.

Question 4

Lipoproteins

Answer 4

Primary transport mechanism for lipids.

Question 5

Lipoproteins

VLDL

Answer 5

Very-low-density lipoproteins. Transport triglycerides from the liver out to the peripheral tissues.

Question 6

Lipoproteins

LDL

Answer 6

Low-density lipoproteins. This is the “bad cholesterol”.
Transports cholesterol to the peripheral tissues.
VLDL gets converted to IDL and then to LDL.

Question 7

Lipoproteins

HDL

Answer 7

High-density lipoproteins. This is “good cholesterol.”
Transports cholesterol to the liver where it gets processed and exits the body.

Question 8

Lipid breakdown

Mechanical breakdown

Answer 8

Occurs in the mouth and stomach.

Question 9

Lipid breakdown

Chemical breakdown

Answer 9

Multiple enzymes (called lipases) help digest lipids.
The primary site of lipase production is the pancreas.

Question 10

Lipid breakdown

Bile salts

Answer 10

In the small intestine, bile will emulsify the fat by mixing it with water.
This results in increased surface area which increases the rate of digestion.

Question 11

Lipid synthesis

Fatty acid synthesis

Answer 11

Synthesized in the cytoplasm of cells from acetyl-CoA molecules.

Question 12

Lipid synthesis

Cholesterol synthesis

Answer 12

Synthesized in the liver.
The rate-limiting step is the production of mevalonate, catalyzed by HMG-CoA reductase.

Question 13

Lipid synthesis

Ketogenesis

Answer 13

During prolonged fasting, excess acetyl-CoA in the liver gets converted to ketone bodies.
The brain can use ketone bodies as a major energy source (ketosis) in starvation or prolonged fasting environments.

Question 14

Lipid transport

Micelles

Answer 14

Spherical structures with hydrophilic heads facing the exterior and hydrophobic tails on the interior.
This allows micelles to be absorbed like a polar molecule but break down nonpolar molecules in the interior.

Question 15

Lipid transport

Direct bloodstream absorption

Answer 15

Short-chain fatty acids are absorbed directly in the intestine.
Long-chain fatty acids get absorbed as micelles.

Question 16

Lipid transport

Chylomicrons

Answer 16

Micelles can form into chylomicrons which transport cholesterol and fatty acids through the lymphatic system.

Question 17

Fatty acid synthesis

Answer 17

Synthesis of fatty acids starting from acetyl-CoA.

Question 18

Fatty acid synthesis

Location

Answer 18

Takes place in the cytoplasm.

Question 19

Fatty acid synthesis

Rate-limiting step

Answer 19

In the initial and rate-limiting step, the enzyme acetyl CoA-carboxylase (ACC) converts acetyl-CoA to malonyl-CoA.

Question 20

Fatty acid synthesis

Fatty acid synthase

Answer 20

The subsequent steps are catalyzed by fatty acid synthase.
Know that it uses reduction with NADPH to link malonyl-CoA units.

Question 21

Fatty acid oxidation (β-oxidation)

Answer 21

Breakdown of fatty acids resulting in Acetyl CoA and electron carriers (NADH, FADH2).

Question 22

Fatty acid oxidation (β-oxidation)

Products

Answer 22

The products in β-oxidation depend on the # of carbons in the original fatty acid.
Fatty acids go through rounds of oxidation. Each round takes off the 2-carbon acetyl-CoA, produces 1 NADH and 1 FADH2.
This continues until only a 2-carbon acetyl-CoA or a 3-carbon propionyl-CoA remains.

Question 23

Fatty acid oxidation (β-oxidation)

Examples

Answer 23

Starting with a 18-carbon fatty acid, there are 8 rounds of oxidation, resulting in 9 acetyl-CoA and 8 NADH and FADH2.
Starting with a 17-carbon fatty acid, there are 7 rounds of oxidation, resulting in 7 acetyl CoA, 7 NADH and FADH2, and 1 propionyl-CoA.

Question 24

Fatty acid oxidation (β-oxidation)

Location

Answer 24

Occurs in the mitochondria within the cell. Occurs in all tissues in the body.

Question 25

Fatty acid oxidation (β-oxidation)

Initial step

Answer 25

Fatty acid is converted to acyl-CoA, consuming one ATP molecule.

Question 26

Fatty acid oxidation (β-oxidation)

Link to other pathways

Answer 26

The product acetyl-CoA can feed into the citric acid cycle or fatty acid synthesis.

Question 27

Fatty acid oxidation (β-oxidation)

Saturated versus unsaturated fatty acids

Answer 27

Unsaturated fatty acids require an additional isomerization step in β-oxidation to convert double bonds in the cis conformation to the trans conformation.

Question 28

Protein catabolism

Answer 28

Breakdown of proteins as an energy source, happens during prolonged starvation state.

Question 29

Protein catabolism

Gluconeogenesis

Answer 29

Glucogenic amino acids can be converted into intermediates of gluconeogenesis.
This includes all amino acids other than leucine and lysine.

Question 30

Protein catabolism

Ketogenesis

Answer 30

Ketogenic amino acids can be converted into ketone bodies to be used as an energy source.
The two amino acids that can only be used for ketogenesis are leucine and lysine.