Fatty Acid Oxidation And Ketone Bodies

Question 1

In which cells is B-oxidation of fatty acids is performed and what is the purpose?

Answer 1

• B-oxidation takes place in mitochondria of well-oxygenated cells with the purpose to provide FADH2 and NADH for the ETC and ATP formation
• The fatty acids are degraded to Acetyl CoAs which join the TCA cycle in most cells. Exception is the liver which will be discussed later on.
• The heart has always a high demand for ATP and it uses B-oxidation followed by the TCA cycle after a meal and also during fasting

Question 2

How much ATP is generated by palmitoyl CoA ?

Answer 2

Palmitoyl CoA generates 131 ATP

Palmitate generates 129 ATP

Question 3

Explain the degradation of Palmitoyl

Answer 3

Stage 1: Palmitoyl CoA B-oxidation generates 8 Acetyl CoAs, 7 FADH2 and 7 NADH

Stage 2: the formed8 Acetyl CoAs enter the TCA cycle. This generates 8x 3NADH2, 8x 1FADH2 and 8 GTP

Stage 3: total in ETC:

B-oxidation:
7 FADH2 generate 14 ATP
7 NADH generate 21 ATP, total 35 ATP

TCA cycle:
24 NADH generates 72 ATP
8 FADH2 generates 16 ATP, total 88 ATP

Question 4

What is metabolic water?

Answer 4

During complete degradation of fatty acids, water is formed which is known as metabolic water

Question 5

B-oxidation of fatty acids is a …

Answer 5

Starting with fatty acyl CoA generating FADH2, NADH and Acetyl COA

Question 6

What are the four general reactions of B-oxidation of fatty acids?

Answer 6

1. Oxidation (forms FADH2)
2. Hydration
3. Oxidation (forms NADH)
4. Thiolysis uses free CoA instead of water and forms Acetyl CoA and a 2 carbons shorter fatty acyl CoA

Question 7

What are the molecules of B-oxidation ?

Answer 7

Fatty acyl (n) CoA —> Enoyl CoA —> 2-Hydroxyacyl CoA —> 3-keto acyl CoA + free CoA

—> Fatty acyl (n-2) CoA+ Acetyl CoA.

Question 8

What are the names of enzymes involved in B-oxidation?

Answer 8

1. Acyl CoA dehydrogenase
2. Hydratase
3. Hydroxyacyl CoA dehydrogenase
4. Thiolase

Question 9

What is the purpose of Acetyl dehydrogenase?

Answer 9

Fatty acyl (n) CoA. —> enoyl CoA

• Acyl CoA dehydrogenass form FADH2
• Group of chain-length specific enzymes: LCAD, MCAD, SCAD

Question 10

What is thiolytic cleavage?

Answer 10

Thiolase uses free CoASH I’m stead of water and generates a shorter fatty acyl CoA instead of a shorter free fatty acid

Question 11

What is the prosthetic group of Acetyl dehydrogenase?

Answer 11

FAD and forms FADH2 that interacts with other foavopriteins which enter the ETC at CoQ. This leads to 2 ATP

Question 12

What are the coenzymes used in B-oxidation?

Answer 12

3-hydroxyacyl CoA dehydrogenase

Acetyl CoA dehydrogenase

Question 13

What is the function of 3-hydroxyacyl CoA dehydrogenase ?

Answer 13

3-hydroxyacyl CoA dehydrogenase uses NAD+ and forms NADH that enters the ETC at complex 1 which leads to 3 ATP

Question 14

Where does B-oxidation take place?

Answer 14

• mitochondria

- peroxisomes

Question 15

Contrast B-oxidation in peroxisomes and mitochondria

Answer 15

Mitochondria

• saturated fatty acids
• unsaturated fatty acids
• Odd-numbered fatty acids
• medium chain fatty acids enter without carnitine shuttle

Peroxisomes:
-Very long chain fatty acids with more than 20 carbons are degraded to long-chain fatty acids

-Dietary branched-chain fatty acids are degraded after using first one time a-oxidation

Question 16

Are fatty acids with double bonds common ? How are they degraded?

Answer 16

• Natural unsaturated fatty acids with cis-double bonds are common
• they are found in position-2 of phospholipids in membranes
• Unsaturated fatty acids need for their eventual degradation during B-oxidation in mitochondria two or more enzymes and NADH

Question 17

What does the body make from odd number fatty acids?

Answer 17

Degradation leads to Acetyl CoAs and to one prop I only CoA (at the end) which is changed to succinyl CoA can be degraded in the TCA cycle

Question 18

Why are very long chain fatty acids first degraded in peroxisomes?

Answer 18

Hydrogen peroxide is wanted for the detoxifying functions of peroxisomes and is generated in fatty acid degeneration

Question 19

Explain hydrogen peroxidase formation of B-oxidation from very long chain fatty acids

Answer 19

B-oxidation of very long chain fatty acids in peroxisomes starts with the different enzyme Acetyl CoA oxidase

FADH2 does not enter the ETC but is instead used fir hydrogen peroxide format

The fatty acyl groups are shortened mostly to medium-chain fatty acids that are transferred to mitochondria for further degradation

Question 20

How can phytanic acid be obtained from Daury and ruminant fat?

Answer 20

Peroxisomal degradation of branched-chain fatty acids one time alpha-oxidation and then finished with B-oxidation

Dairy and ruminant fat contains phytanic acid: a 20 C branched chain fatty acid derived from phytol (Chlorophyll)

Question 21

What is the purposes of humps in camels?

Answer 21

The camel uses its fat deposits in its humps for generation of energy and metabolic water during complete long-chain fatty acid oxidation

Question 22

Why can the kangaroo rat live indefinitely without water?

Answer 22

The kangaroo rat can live indefinitely without drinking water. It lives in desert on seeds which are rich in lipids but contain no water.

The metabolic water is sufficient for alol the water needs

Question 23

How do animals not die of hunger/thirst in hibernation?

Answer 23

Many animals hibernate and use their fat deposits fir energy metabolism and formation of metabolic water

Question 24

When does the liver usually use free fatty acids?

Answer 24

The liver uses B-oxidation of fatty acids mainly during fasting or flight and fight situations when it takes up free fatty acids from blood

Question 25

What hormones contribute to liver undergoing B-fatty acid oxidation?

Answer 25

Free fatty acids released from fat cells into blood due to low insulin levels and high epinephrine levels Glucagon causesswitchwes liver metabolism from glycolysis to gluconeogenesis. The liver has to perform B-oxidation of fatty acids form ATP formation and to generate NADH and Acetyl CoA for allosteric regulation and activation of gluconeogenesis Hepatic TCA cycle is inhibited and the formed Acetyl CoAs are used to form ketone bodies during starvation

Question 26

What are ketone bodies?

Answer 26

The term ketone bodies refers to 3-hydroxybutyrate (B-hydroxybutyrate), and acetoacetate which are formed only in the liver Ketone bodies are released into the blood and are fuel extra-hepatic tissues

Question 27

What is acetone? How is it formed?

Answer 27

Acetone is a ketone body that is spontaneously formed from acetoacetate and is exhaled

Question 28

What processes are activated by alanine, lactate, glutamine and glycerol in blood?

Answer 28

Gluconeogenesis which increases glucose 6-p then free glucise

Question 29

What processes do fatty acids in blood activate/inhibit?

Answer 29

B-oxidation Inhibits PDH, TCA cycle inhibited Energy and allosteric regulation and ketone body synthesis

Question 30

Where does synthesis and release of ketone bodies during fasting?

Answer 30

Only in hepatocytes

Question 31

During fasting many free fatty acids are...

Answer 31

Taken up from the blood. The carnitine shuttle is not inhibitedby malonyl CoA and many fatty acyl-groups enter the mitochondrial matrix for B-oxidation

Question 32

Active B-oxidation leads to...

Answer 32

High levels of NADH and oxaloacetate is used to form malate for gluconeogenesis. The high Acetyl CoA level leads to hepatic ketone body synthesis

Question 33

Outline ketone body synthesis

Answer 33

Takes place only in liver mitochondria -In humans with a normal diet, ketone body synthesis takes place mainly during fasting 1. Acetoacetyl CoA and Acetyl CoA that are generated during B-oxidation are used 2. Acetoacetyl CoA cannot leave mitochondria. Only the free ketone body acetoacetate can be released 3. HMG CoA is formed from acetoacetate CoA and Acetyl CoA 4. HMG CoA can be cleaved to the first ketone body acetoacetate

Question 34

How is ketone body synthesis regulated?

Answer 34

Mitochondrial HMG CoA synthase is only found in significant amounts in hepatic mitochondria The enzyme catalyzes the regulated step and the main regulator for ketone body synthesis is the concentration of Acetyl CoA I’m addition, glucagon leads via cAMP to increased transcription of HMG CoA synthase

Question 35

Which ketone bodies are released in the blood?

Answer 35

Hepatic HMG CoA lyase cleaves HMG CoA to acetoacetate Acetoacetate is either directly released into the blood or it is reduced to the stable 3-hydroxybutyrate which is also released into the blood

Question 36

What is the advantage of ketone bodies?

Answer 36

1. Formation of acetoacetate from 3-hydroxybutyrate generates NADH(3 ATP) 2. Acetoacetate is activated to acetoacetyl CoA without input of ATP by the enzyme this phrase. No ATP input required 3. Acetoacetate and succinyl CoA of the TCA cycle are used to form acetoacetyl CoA which is cleaved to 2 Acetyl CoAs entering new TCA cycles Note: the liver itself cannot use ketone bodies as thiophorase is absent in hepatocytes