Fatty Acid Oxidation and Ketone Body Production- Lecture 67

Question 1

What is the general structure of triglycerides?

Answer 1

CH3-(CH2)n-COOH

with a glycerol backbone and three fatty-acids in ester linkages

Question 2

Fatty acids that contain double bonds in the methylenes are called ______, and fatty acids with more than one double bond are called _______.

Answer 2

unsaturated fatty acids

polyunsaturated fatty acids

Question 3

What are the functions of fatty acids?

Answer 3

major source of energy for most tissues
major storage form of energy as triglycerides
compose phospholipids and glycolipids of biological membranes
produce signal transduction molecules (eg. inositol, phosphates, diacylglycerol)
produce prostoglandins and leukotrienes

Question 4

Fatty acids and glycerol are taken up mainly by _____, and triglycerides are resynthesized and stored largely in _____.

Answer 4

adipose tissue

adipose tissue

Question 5

Describe the naming system for fatty acids.

Answer 5

C:D ^n
C= number of carbons
D= number of double bonds
^ (delta)n= double bond at n carbon

Question 6

The ______ in adipose tissue is activated by ______ via ______.

Answer 6

hormone-sensitive lipase
glucagon, epinephrine, or norepinephrine
cAMP-dependent PKA phosphorylation

Question 7

Fatty acids exit the adipose tissue bound to _____.

Answer 7

albumin

Question 8

Why does the brain require glucose constantly for energy?

Answer 8

because albumin bound fatty acids cannot cross the blood brain barrier among other more minor reasons

Question 9

What is the net reaction for triglyceride synthesis?

Answer 9

glyceron + 3 fatty acid molecules triglyceride + 3 water molecules

Question 10

Name the pathways in which FA-CoA can be used.

Answer 10

beta oxidation
triglycerides
phospholipids, sphingolipids, cholesterol esters)

Question 11

Describe the pathway of beta oxidation of fatty acids (even chains).

Answer 11

Fatty acid + FAD –> FADH2 + Trans-delta squared-enoyl-CoA
Trans-delta squared-enoyl CoA + H20–> 3-L-hydroxyacyl-CoA
3-L-hydroxyacyl-CoA + NAD+ –> NADH + beta-ketoacyl-CoA
beta-ketoacyl-CoA + HSCoA –> fatty acyl-CoA + acetyl-CoA
repeated until only two Carbons are left

Question 12

What is the net energy you would get if you completely broke down a C16FA via beta-oxidation?

Answer 12

8 Acetyl-CoA --> 80 ATP
7 FADH2 --> 10.5 ATP
7 NADH --> 17.5 ATP
-2 ATP consumed to activate the FA
-------------------------------
106 ATP (net total)

Question 13

How does long chain fatty acyl CoA enter the mito?

Answer 13

carnitine shuttle

Question 14

Describe the pathway of the carnitine shuttle.

Answer 14

carnitine is re-synthesized from lysine
FA~CoA –> fatty acytl-carnitine (via acytl-carnitine transferase 1 (ACT1))
translocation across mitochondrial membrane (via CACT)
fatty acytl-carnitine –> FA~CoA (via ACT2 using intramitochondrial CoASH)

Question 15

What is the difference between odd and even chain fatty acid breakdown by beta-oxidation.

Answer 15

the final spiral will produce acetyl CoA plus 3 Carbon propionyl CoA (rather than 2 acetyl CoA)

Question 16

How is propionyl further metabolized?

Answer 16

propionyl-CoA + ATP + CO2 –> ADP + methylmalonyl-CoA (via propionyl-CoA carboxylase with biotin cofactor)
methylmalonyl-CoA –> succinyl CoA (via methylmalonyl-CoA mutase with B12 cofactor)

Question 17

What is the rate-limiting enzyme of fatty acid synthesis?

Answer 17

malonyl CoA

Question 18

What regulates beta-oxidation?

Answer 18

availability of fatty acids via activated hormone-sensitive lipase
availability of carnitine
malonyl CoA inhibits carnitine acyl transferase 1 and 2
rate of the electron transport chain

Question 19

What is ketogenesis?

Answer 19

alternative pathway used in the liver (and to some extent the kidney) for acetyl-CoA metabolism when it cannot enter the TCA cycle (eg. when OAA is depleted by gluconeogenesis)

Question 20

Why does ketogenesis normally only occur in the liver?

Answer 20

liver has a hard time keeping TCA cycle b/c OAA keeps getting shunted out –> no place to keep Acetyl CoA –> builds up and starts to stop fatty acid synthesis

Question 21

“Fruity breath” is the smell of ______ in ______.

Answer 21

acetone

people with diabetes, on low carb diets, and alcoholics

Question 22

Describe the pathway of ketogenesis.

Answer 22

2 acetyl-CoA CoASH + acetoacetly CoA (via thiolase)
acetoacetyl CoA –> beta-hydroxyl beta-methyl glutaryl CoA (HMGCoA) (viaHMG CoA synthase)
HMGCoA –> acetyl CoA + acetoacetate (via HMG CoA lyase)
acetoacetate –> CO2 + acetone
OR
acetoacetate + NADH –> NAD+ + beta-OH butyrate (via beta-OH butyrate dehydrogenase)

Question 23

How can beta-OH butyrate be further metabolized?

Answer 23

beta-OH butyrate + NAD+ NADH + acetoacetate (via beta-OH butyrate dehydrogenase)
acetoacetate + succnyl-CoA –> acetoacetyl-CoA + succinate (via beta-ketoacetyl-CoA transferase)
acetoacetyl-CoA + CoASH 2 acetyl-CoA (via thiolase)

Question 24

Ketone bodies made in the ____ are valuable sources of fuel for other tissues, especially _____.

Answer 24

liver

muscle, heart, and kidney cortex

Question 25

How are ketone bodies removed from their origin of synthesis?

Answer 25

removed from the mito on carrier 5 | leave the liver in blood circulation

Question 26

What is the problem with having high levels of ketone bodies in the blood (ketosis)?

Answer 26

strong acids that alter blood pH

Question 27

Beta-ketoacetyl-CoA transferase is not present in _____, but can be induced _______.

Answer 27

the brain | under prolonged periods of stressful conditions (eg. starvation)

Question 28

What is the function of the peroxisomal fatty acid oxidation pathway?

Answer 28

preferentially oxidizes very long chain fatty acids (eg. C22-26) two carbons at a time, yielding an acetyl-CoA each spiral until a medium chain (C10-12) is produced and can enter the mito beta-oxidation pathway produces H2O2 as the electron carrier rather than FADH2