fatty acid catabolism

Question 1

what is B-oxidation

Answer 1

a four-step enzyme catalyzed process of oxidative removal of 2-carbon from FA to form acetyl-CoA
** liver and heart derive 80% energy from FA oxidation

Question 2

4 reasons why triacyglycerols are the best storage fuel

Answer 2

1. FA chains are highly reduced compunds
2. yield 2 times more energy than CHO and protein
3. insoluble in water- does not increase osmolarity
4. relatively inert - nor risk of undesirable reactions

Question 3

8 steps lipids digestion and transport

Answer 3

1. Bile salts emulsify dietary fats in the small intestine, forming mixed micelles
   
   2. Intestinal lipases degrade triacyglycerols to diacylglycerol, monoacyglycerol, Free FA and glycerol
   3. FA and other breakdown products are taken up by the intstinal mucusoa and converted into triacyglycerols
   4. Triacylglycerols are incorporated, with cholesterol and apolipoproteins, into chylomicrons
   5. Chylomicrons move through the lymphatic system and bloodstream to tissues
   6. Lipoprotein lipas, activated by apoC-II in the capillary, converts triacyglycerol to FA and glycerol
2. FA are oxidized as fuel or reesterified for storage

Question 4

steps for lipids mobilization from storage (lipid droplet in adipocyte through cells)

Answer 4

1. Glucagon binds to its receptor in the adipocythe tissue
   
   2. Stimulation of adenyl cyclase via a G protein to produce cAMP which activates PKA
   3. PKA phosphorylates perilipin and HSL
   4. when peripilin is phosphorylates, the CGI which are associated with them will be desassociated and moves to ATGL, an enzyme which become active only when it is associated with CGI.
   5. ATGL attacks triacyglycerol and remove the first FA, so they have now diacyglycerol
   6. HSL will break it down to one FA and finally to create monoacyglycerol (phosphorylated peripilin associated with phosphorylated HSL allows it to accees to the surface of the lipid droplet and do this)
   7. MGL will break the bound between glycerol and the last FA (hydrolyse monoacyglycerol)
   8. FA leaves the adipocyte, bind serum albumin in the blood, and are carried in the blood; they are released form the albumin and then
   9. Enter a myocyte via specific FA transporter
      In the myocyte, FA are oxidized to CO2, and the nergy of the oxidation is conserved in ATP, which fuels muscle contraction and other energy-requiring metabolism in the myocyte

Question 5

what happens to glycerol

Answer 5

• contribute to 5% of the energy from TG
  1. phosphorylation of the glycerol by glycerol kinase to create L-glycerol 3-phosphate (use one ATP)
  2. oxidation by glycerol 3-phosphate dehydrogenase to create dihydroxyacetone phosphate (create one NADH)
  3. isomerization by triose phosphate isomerase to create D-glyceraldehyde 3-phosphate which will go through glycolysis

Question 6

what is the role of fatty acyl-CoA synthetase

Answer 6

it will activate the FA by creating fatty acyl-CoA in the outer mitochondrial membrane because FA has to be activate to

1. do the oxidation (need to be activated before being transported to the mitochondria)
2. to synthesize longer FA to create membrane lipids

Question 7

steps for the transport of FA from the cytosol through the matrix of the mitochondria

Answer 7

1. FA destined for mitochondrial oxidation are attached to the hydroxyl group of carnitine to form fatty acyl-carnitine which is catalyzed by carnitine acyltransferification I (in the outer membrane)
   
   2. Fatty acyl-carnitine moves into the matrix by facilitated diffusion through the transporter in the inner membrane
      ** its transport through the intermembrane space occurs through large pores in the outer membrane
      In the matrix, the acyl group is transferred through mitochondrial coenzyme A by carnitine acyltransferase II, freeing carnitine to return in the intermembrane space (via acyl-carnitine transporter) and regenerating fatty acyl-CoA

Question 8

4 steps with 4 enzymes of the oxidation of fat

Answer 8

1. acyl-CoA dehydrogenase (one FAD+ is reduce to FADH2 and the electrons are transferred to ETF where it will go in the respiratory chain): will create a double bond between C2 and C3
2. enoyl-CoA hydratase (use a molecule of H20)
3. B-hydroxyacyl-CoA dehydrogenase (NAD+ reduce in NADH)
4. acyl-CoA acetyltransferase (thiolase) : In the last step, there is the a reaction between B-Ketoacyl-CoA and a molecule of free coenzyme A to splitt off the carboxyl-terminal two-carbon fragment of the original FA as acetyl-CoA

Question 9

B-oxidation of 16C FA yields what

Answer 9

8 acetyl-CoA, 7 FADH2, 7 NADH, 7H+

** NADH and FADH2 yield 28 ATP

Question 10

what happens during B-oxidation of unsaturated and polyunsaturated FA

Answer 10

For unsaturated:

• It requires another enzyme (enoyl-CoA isomerase) that takes the 2 double bonds and transform them in one double bond between C3-C4
• ** everytime there is an isomerization step, there is one less FADH2 in the process

For polyunsaturated (more than one double bonds):
It requires 2 more enzymes (dienoyl-CoA reductase and enoyl-CoA isomerase)

Question 11

enzymes requires for B-oxidation of odd-number FA

Answer 11

1. propionyl-CoA carboxylase which contain the cofactor biotin transform propionyl-CoA to D-Methylmalonyl-CoA
2. methylmalonyl-CoA epimerase to convert D-methyl to L-methyl
3. methylmalonyl-CoA mutase (withc cofactor B12) to convert into succinyl-CoA whoich will go in the citric acid cycle

Question 12

what do malonyl-CoA

Answer 12

** it is the first intermediate in of FA synthesis**

it inhibits Carnitine Acetyl-transferase I

Question 13

what inhibits acyl-CoA dehydrogenase

Answer 13

high ratio of NADH/NAD+

Question 14

where is w oxidation, substrate + 3 enzymes

Answer 14

• in the endoplasmic reticulum of kidney and liver
• preffered substrates: FA of 10 or 12C
  1. mixed-function oxidase (NADPH to NADP+)
  2. alcohol dehydrogenase (NAD+ to NADH)
  3. aldehyde dehydrogenase (NAD+ to NADH), the final product is a FA with carboxyl group at each end

Question 15

ketone bodies

Answer 15

water soluble energy molecules

• produce in the liver
• acetone (low) is exhaled through respiration
• acetoacetate and B-hydroxybutyrate are transported to other tissues via blood
• converted back to acetyl-CoA

Question 16

steps ketone synthesis with every enzyme

Answer 16

• • in the mitochondri of the liver**
• • for people in starvation or diabetes
    1. enzyme: thiolase = 2 acetyl-CoA into 1 acetoacetyl-CoA
    2. enzyme: HMG-CoA synthase (also present in the cytoplasm) = B-hydroxy-B-methylglutaryl-CoA by te utilisation of one acetyl-CoA
    3. enzyme: HGM-Coa lyase = acetoacetate with a release of acetyl-coa
    4. 2 possibilities:
• enzyme: acetoacetate decarboxylase = acetone with a relaease of CO2
• ensyme: D-Bhydroxybutyrate dehydrogenase = D-B-hydroxybutyrate with a release of NAD+

Question 17

steps for ketone bodies: catabolism

Answer 17

1. enzyme: D-B-hydroxybutyrate dehydrogenase converts D-Bhydroxybutyrate into acetoacetate
2. enzyme: B-ketoacyl-Coa transferase = use a succinyl-coa to produce acetoacyl-coa (*** the enzyme is absent in the liver)
3. enzyme: thiolase which produce 2 acetyl-coa