lipid metabolism

Question 1

Fatty acids are stored in the form of…

Answer 1

Triacylglycerols

Question 2

when hydrolysed, fatty acids can yield …

Answer 2

9kcal/g

Question 3

carbs and amino acids can yield…

Answer 3

4kcal/g

Question 4

Fatty acids require what process to be released from triaglycerols and how is the process initiated?

Answer 4

Fatty acids require hydrolysis. c1 and c3 of glycerol backbone are initiated by adipose trycylglyceride lipase & c2 is initiated by monocylpglycerol lipase.

Question 5

Describe the initiator adipose triglyceride lipase. (for c1 & c3)

Answer 5

504 amino acids in length with a weight of 55 kDa. The weight limiting step of triacylglycerol breakdown. Occurs on lipid droplets & in cytosol. produces either 2,3- or 1,-3 diacylglycerol. catalytic activity strongly enhanced by CGI-58.

Question 6

Describe initiator Hormone sensitive lipase. (for c1 & c3)

Answer 6

786 amino acids in length with molecular weight 85.5kDa. hydrolysis occurs. 2 steps; step 1 cleaves the covalent ester bond between glycerol and the fatty acid. step 2, water displaces the covalent intermediate.
Cleaves the 1- & 3- ester bonds 3-4- fold faster than the 2- ester bonds.

Question 7

Describe initiator monoacylglycerol lipase. (for c2)

Answer 7

303 amino acids in the length, 33kDa. Found in many tissues, ‘housekeeping’ enzyme. Hydrolysis 1-,2- diacylglycerols at same rate, although ABHD6 shows preference.

Question 8

Glycerol released cannot be metabolised by adipocytes why?

Answer 8

They do not have glycerol kinase. So glycerol is transported in blood to liver which can will subject it to 1 of 3 fates which all require production of glycerol 3-phosphate by glycerol kinase.

Question 9

Tell me about fate 1 of glycerol.

Answer 9

Dependent upon conversion of glycerol 3-phosphate to dihydroxyacetone phosphate by enzyme glycerol 3-phosphate dehydrogenase.

Question 10

Explain about fate 2 of glycerol; dihydroxyacetone phosphate.

Answer 10

It is a glycolytic/ gluceonogenenic intermediate so 2 possible fates… glucose or pyruvate.

Question 11

Tell me about fate 3 of glycerol.

Answer 11

glycerol 3 - phosphate can be used to produce more triacylglycerides, which the liver stores as very low density lipoprotein (VLDL)

Question 12

Free fatty acids move through plasma of adiposites to bloodstream. 99% of FFAs bind to albumin. How many binding sites does albumin have?

Answer 12

7 sites for fatty acids.

Question 13

Depending on chain length, FFAs can enter cells 2 ways…

Answer 13

passive diffusion (short 2-6Cs & medium 7-12 Cs. or Specialised FA transport proteins ( long chain 13-21+ Cs)

Question 14

FFAs are toxic to cells. why?

Answer 14

The COO- makes them amphipathic (hydrophilic & hydrophobic) and thus would act like detergents if not neutralised.

Question 15

How is the COO- in FFAs neutralised?

Answer 15

By acetyl CoA synthase, also known as thiokinase. The reaction is driven forward by pyrophosphatase. Once the Acetyl-CoA has been formed it can follow 2 paths… re-esterification into triacylglycerols or B-oxidation to the citric acid cycle and ketone bodies.

Question 16

Tell me about B-oxidation of fatty acids. part 1

Answer 16

Major oxidation pathway for FA catabolism. Takes place in mitochondrial matrix. 2C fragments removed from fatty acyl CoA to produce acetyl CoA which can be oxidised in the citrate cycle.

Question 17

Tell me about B-oxidation of FA part 2

Answer 17

It is the rate limiting step as fatty acyl CoA molecules cannot diffuse into the mitochondrial.

Question 18

The passage of fatty acyl CoA from cytosol to mitochondrial matrix is mediated by a special transport system called what and explain it.

Answer 18

The Carnitine shuttle. Carnitine replaces CoA in the fatty acyl CoA by ‘carnitine palmitoyltransferase I’ (CPT I) to form acyl carnitine. This is transported through mitochondrial membrane by a translocase.

Question 19

In the mitochondrial matrix, carintine palitoyltransferase II (CPT II) converts what to what?

Answer 19

It converts acyl carnitine to fatty acyl CoA. Which can now undergo B-oxidation. Carnitine is then transported back to the inner membrane space by translocase for further use.

Question 20

What does the b-oxidation cycle produce and what is the net result?

Answer 20

It produces 1 acetyl CoA, 1 Fatty Acyl Coa (minus 2C), 1 NADH, 1 FADH2. Net production results shortened FA by 2 carbon atoms .

Question 21

Explain step 1 of B-oxidation of FAs.

Answer 21

Acyl CoA dehydrogenase. Specific to chain length, long, medium & short acyl CoA dehydrogenases. These enzymes catalyse the formation of a double bond between alpha and beta carbons on acyl CoA molecules by removing 2 electrons, producing one molecule of FADH2, which eventually accounts for 2 ATP molecule produced in ETP.

Question 22

Explain step 2 of the B-oxidation of FAs

Answer 22

Enoyl CoA hydratase. Performs a hydration step of the double bond between alpha and beta carbons. Results in the a hydroxyl group (OH-) to the beta carbon & a proton (H+) to the alpha carbon. No energy production.

Question 23

Explain step 3 of B-oxidation of FAs.

Answer 23

3 (b)- hydroxyl acyl CoA dehydrogenase. Electrons and 2 protons are removed from the hydroxyl group, and the attached beta carbon to oxidise the beta carbon & produce a molecule of NADH. Each NADH results in 3 ATP molecules from ETC.

Question 24

Explain step 4 of B-oxidation of FAs.

Answer 24

3 (B)-keto thiolase. Cleavage of bond between alpha and beta carbon by CoA. The reaction produces one molecule of acetyl CoA & a fatty acetyl CoA 2 carbons shorter. Repeated until even chain FA has converted to acetyl CoA.

Question 25

ATP from Palmitoyl CoA?

Answer 25

7 FADH2 produces 14 ATP & 7 NADH produces 21 ATP & 8 Acetyl CoA produces 96 ATP.

Question 26

What do ketone bodies include?

Answer 26

Acetoacetate, 3-hydroxybutyrate, acetone.

Question 27

Where are ketone bodies synthesised?

Answer 27

In the mitochondria of liver cells, transported in the blood to peripheral tissues.

Question 28

When are ketone bodies produced? Give an example.

Answer 28

During periods when the amount of acetyl CoA produced EXCEEDS the oxidative capacity of the liver. E.g. during starvation. Acetyl CoAs can be joined together to form ketone bodies. Fueled by skeletal and cardiac muscle, kidney and 70% of brain.