Lecture 15: Lipid metabolism

Question 1

What are the biological functions of lipids?

Answer 1

Cell membranes
Energy storage
Steroid hormones
Metabolism

Question 2

What make up a triglyceride?

Answer 2

Glycerol + 3 FAs

Question 3

What fats are for storage?

Answer 3

TGs

Question 4

What fats are used for membranes?

Answer 4

Phospholipids - glycerophospholipids and sphingolipids

Glycolipids - sphingolipids

Question 5

What make up a glycerophospholipid?

Answer 5

Glycerol + 2 FA + phosphate + alcohol

Question 6

What make up a sphingolipid (phospholipid)?

Answer 6

Sphingosine + FA + phosphate + choline

Question 7

What make up a sphingolipid (glycolipid)?

Answer 7

Sphingosine + FA + mono or oligosaccharide

Question 8

What is beta-oxidation?

Answer 8

Oxidation of long chain fatty acids to 2 carbon fragments in the form of acetyl-CoA

Question 9

Where does b-oxidation occur?

Answer 9

In the mitochondria and in peroxisome

Question 10

How are fatty acids moved into the mitochondrial matrix?

Answer 10

Carnitine carrier protein - the acyl is transferred from the coenzyme-A to carnitine, this is transferred across the membrane into the matrix where it then detaches from the carnitine and bind to CoA present in the matrix.

Each transfer of FA requires carnitine palitoyl transferase (1 or 2)

Question 11

Where is carnitine palmitoyl transferase 1 found?

Answer 11

Cytosol

Question 12

Where is carnitine palmitoyl transferase 2 found?

Answer 12

Mitochondrial matrix

Question 13

What is the rate limiting step of b-oxidation?

Answer 13

Transfer of acyl groups across the mitochondrial matrix

Question 14

What are the three stages of b-oxidation?

Answer 14

1: FA activated by attachment of Coenzyme A
2: transfer of acyl across mitochondrial membrane
3: progressive oxidation FA by removal of 2 carbon units to form acetyl-coA (which enters citric acid cycle)

Question 15

What three molecules are formed during each cycle of b-oxidation?

Answer 15

1 acetyl coA
1 FADH2
1 NADH

Question 16

What is the first reaction for the removal of acetyl coA from fatty acyl-coA?

Answer 16

Fatty acyl CoA to trans-enoyl CoA

Enzyme = acyl-coA dehydrogenase

Question 17

A mutation in which enzyme will cause SIDS?

Answer 17

Acyl-coA dehydrogenase

Question 18

Where does fatty acid synthesis occur?

Answer 18

In the cytosol (mainly in the liver and adipocytes)

Question 19

How does acetyl-coA get out of the mitochondria?

Answer 19

By the citrate malate cycle

Question 20

Describe the citrate malate cycle.

Answer 20

OAA + acetyl-coA –> citrate

Citrate leaves the cell by tricarboxylate transporter

In the cytosol citrate is converted back to OAA and acetyl-coA

Acetyl-coA used for FA synthesis

OAA converted to malate then pyruvate and pyruvate is shuttled back into the mitochondria by the pyruvate transported

Question 21

What is the rate limiting step of FA synthesis?

Answer 21

Carboxylation of acetyl-CoA to make malonyl-CoA

Catalysed by acetyl CoA carboxylase

Question 22

In FA synthesis, what is acetyl CoA first converted into?

Answer 22

Malonyl-CoA

Question 23

How is FA synthase regulated?

Answer 23

Malonyl-CoA and acetyl-CoA both bing to FA synthase

Question 24

What type of reaction adds further C2 units in FA synthesis?

Answer 24

Condensation reactions

Question 25

How is acetyl-CoA carboxylase regulated?

Answer 25

Subject to phosphorylation under the control of glucagon (inactivates) and insulin (activates)

Question 26

What enzyme catalyses the formation of cholesterol esters?

Answer 26

Acyl-CoA Cholesterol Acyltransferase (ACAT)

Question 27

How is cholesterol stored?

Answer 27

In the form of cholesterol esters

Question 28

What are bile acids used for?

Answer 28

Lipid digestion Lipid absorption Cholesterol excretion

Question 29

What is the rate limiting step of cholesterol synthesis?

Answer 29

Conversion of HMG-CoA to Mevalonate Enzyme: HMG-CoA Reductase

Question 30

Where is the major site of cholesterol synthesis?

Answer 30

Liver | some in intestine and adrenal cortex

Question 31

What is the target for statins?

Answer 31

HMG-CoA reductase

Question 32

How is HMG-CoA reductase regulated?

Answer 32

Both cholesterol and mevalonate are feedback inhibitors

Question 33

What do chylomicrons transport?

Answer 33

Dietary TGs to muscle and adipose tissue and dietary cholesterol to the liver

Question 34

What do VLDLs transport?

Answer 34

Endogenous TGs and cholesterol

Question 35

What do LDLs transport?

Answer 35

Cholesterol from the liver to tissues

Question 36

What do HDLs transport?

Answer 36

Cholesterol from tissues to liver

Question 37

What are the two stages of dietary TG digestion?

Answer 37

1: emulsification by bile acids 2: hydrolysis by the enzyme pancreatic triacylglycerol lipase

Question 38

What is PCSK9?

Answer 38

Binds to LDL receptors and cause their degradation

Question 39

What is SREBP?

Answer 39

Increases expression of LDL receptors in response to low cholesterol