Integration of fat and carbohydrate metabolism

Question 1

What does Lipolysis do ?

Answer 1

Lipolysis generates fatty acids (used as fuel by many tissues) and glycerol (either for glycolytic or the gluconeogenic pathway)

Question 2

The fatty acids incorporated into triacylglycerols in adipose tissue are made accessible in three
stages ?

Answer 2

1. Degradation of TAG to release fatty acids and glycerol into the blood for transport to energy-requiring tissues
2. Activation of the fatty acids and transport into the mitochondria for oxidation
3. Degradation of the fatty acids to acetyl CoA for processing by the citric acid cycle

Question 3

Where are Triacylglycerols stored in ?

Answer 3

Adipocytes in a lipid droplet

Question 4

What phosphorylates perilipin?

Answer 4

Protein kinase A phosphorylates perilipin, which is associated with the lipid droplet, and hormone-sensitive lipase (HS lipase)

Question 5

What does phosphorylation of perilipin result in ?

Answer 5

The activation of adipocyte triacylglyceride lipase (ATGL)

Question 6

What does adipocyte triacylglyceride lipase (ATGL) initiate ?

Answer 6

The breakdown of lipids

Question 7

What happens to the glycerol released during lipolysis ?

Answer 7

Absorbed by the liver for use in glycolysis or gluconeogenesis

Question 8

So what is Adipocyte Triglyceride Lipase stimulated and inhibited by ?

Answer 8

• Stimulated by Glucagon, adrenaline, ACTH, sympathetic NS

- Inhibited by insulin

Question 9

Fatty acid degradation consists of four steps that are repeated:

Answer 9

• An oxidation
• A hydration
• Another oxidation
• Followed by thiolysis

Question 10

What is fatty acid degradation also called and why ?

Answer 10

It’s also called β-oxidation because oxidation occurs at the β-carbon atom

Question 11

What is generated in each round of fatty acid oxidation ?

Answer 11

Acetyl CoA, NADH and FADH2

Question 12

Transportation of fatty acids into mitochondria ?

Answer 12

• Small (< 12 carbons) fatty acids diffuse freely across mitochondrial membrane
• Larger fatty acids (most free fatty acids) are transported via acyl-carnitine/carnitine transporter

Question 13

Explain the start of the transportation of fatty acids into mitochondria ?

Answer 13

After being activated by linkage to CoA, the fatty acid is transferred to carnitine, a reaction catalysed by carnitine acyltransferase I, for transport into the mitochondria. A translocase transports the acyl carnitine into the mitochondria.

Question 14

In the mitochondria, what does the arnitine acyltransferase II
transfers ?

Answer 14

The fatty acid to CoA. The fatty acyl CoA is now ready to be degraded

Question 15

When is Malonyl CoA generated ? and what does it do ?

Answer 15

Malonyl CoA generated during FA synthesis inhibits carnitine acyltransferase 1 and prevents
entry of acyl CoA into mitochondria and its subsequent oxidation by beta-oxidation

Question 16

What can happen to the Pyruvate in the mitochondria?

Answer 16

It can either:

• Converted to Acetyl CoA by PDH
• Converted to oxaloacetate by pyruvate carboxylase

Question 17

When making fats have to convert acetylCoA into citrate using oxaloacetate, because?

Answer 17

The membrane is impermeable to acetyl CoA

Question 18

Where is Citrate transported to? and cleaved by ?

Answer 18

Citrate is transported to the cytoplasm and cleaved by ATP-citrate lyase to generate acetyl CoA for fatty acid synthesis

Question 19

Fatty acids are built in several
passes, processing one
acetate unit at a time. Where is the acetate coming from ?

Answer 19

The acetate is coming from

activated malonate in the form of malonyl-CoA

Question 20

What is the committed step of fatty acid synthesis ?

Answer 20

• The formation of malonyl CoA
• Catalysed by Acetyl CoA
  carboxylase – requires a biotin cofactor

Question 21

What are Citrate (+ve) and palmitoyl-CoA (-ve) and what does it affect ?

Answer 21

Citrate (+ve) and palmitoyl-CoA (-ve) are allosteric regulators affecting
polymerisation/depolymerisation and activity of Acetyl CoA Carboxylase (ACC)

Question 22

Role of Insulin in regulation of ACC ?

Answer 22

Insulin activates PP2, which dephosphorylates and activates ACC

Question 23

Role of Glucagon in regulation of ACC ?

Answer 23

Glucagon activates 5‘AMP-dependent protein kinase: AMPKK – also stimulated by high AMP, which phosphorylates and deactivates ACC. Glucagon will also inhibit PP1 (via PKA and inhibitor-1)

Question 24

ADP produced by synthetic reactions is converted to ?

Answer 24

ATP and AMP by adenylate kinase

Question 25

The role of AMPK in energy homeostasis ?

Answer 25

• AMP activates “AMP activated protein kinase” (AMPK), which reciprocally regulates ATP-consuming and ATP-generating pathways by phosphorylating key enzymes