Fatty Acid Catabolism

Question 1

What is Fatty Acid Catabolism?

Answer 1

The generation of energy via fatty acid oxidation

Question 2

What is Triacylglycerol?

Answer 2

Fat. it is a hydrophobic, neutral molecule made from the reaction of an OH group on glycerol with the COO- group of fatty acids.

Roughly 90% of dietary lipids are triacylglycerol

Question 3

What are fatty acids made up of?

Answer 3

They are made up of long, hydrophobic hydrocarbon chains and a carboxylic acid polar group

Question 4

What are the 3 sources of fat available for oxidation?

Answer 4

• Dietary fat: What we directly eat (things that are digested, absorbed, burned, or deposited within us)
• Excess dietary fat stored within Adipose tissue
• Excess carbohydrates or Proteins converted into fat within the liver and transported to adipose tissue

Question 5

What is fat’s function?

Answer 5

• Stored fat acts as a major energy source when there is no carbohydrates available
• Serves as a source of fatty acids for important cellular functions
• Provides insulation and good complexion for the body (without it, we look sickly ill)

Question 6

What is the importance of Bile Acids or Salts for Fatty Acid Catabolism?

Answer 6

• Because fat molecules are extremely hydrophobic, they are present as oil droplets after ingestion and need to be emulsified (partially solubilized)
• Bile acids produced in the liver are stored in the gallbladder which are then released into the intestines to emulsify fat molecules
• Bile acids are amphipathic, meaning they are detergent-like molecules and can bind to both hydrophobic and hydrophilic molecules.

Question 7

What are some important players involved in lipid digestion and transport?

Answer 7

• Bile Acids
• Pancreatic Lipases (digest fat)
• Bile Acid and Fatty Acid Binding Proteins: facilitate absorption of lipids in intestine
• Intestinal Fatty Acid Binding Proteins (I-FABP) : Binds to fatty acids and protect cells from detergent-like behaviour of fatty acids
• Chylomicrons: Transports cholesterol and lipids from intestines to adipose tissue via blood
• Lipoprotein Lipase: Digests triglycerides into fatty acids and glycerol

Question 8

What are the different lipoproteins used in Lipid transport?

Answer 8

• VLDL (Very Low-Density Lipoproteins)
• IDL (Intermediate Density Lipoproteins)
• LDl (Low-Density Lipoproteins)
• HDl (High-Density Lipoproteins)

Question 9

How are the different lipoproteins used in Lipid Transport?

Answer 9

• VLDL are used to transport triacylglycerols (fats) and cholesterol from the liver to adipose and muscle tissues.
• VLDL then appears as IDL after giving up their triacylglycerols, and then as LDL.
• IDL’s and LDL’s are then taken back to the liver via receptor mediated endocytosis
• HDL’s are made via the degradation products of other lipoproteins and then used to mop up excess cholesterol from other tissues and deliver it to the liver.

Question 10

How is stored fat utilized?

Answer 10

• Low blood glucose levels and energy requirements trigger the secretion of epinephrine and glucagon hormones.
• This activates Adenylate Cyclase
• Which produces cAMP
• Which activates cAMP-dependant protein kinase
• Which phosphorylates and activates triacylglycerol lipase
• Which releases fatty acids into the blood
• Which is then transported via the blood to muscle tissues
• Where B-oxidation of FA’s takes place to produce acetyl-CoA which enters the CAC and creates energy.

Question 11

How is Glycerol catabolised after Lipase reaction?

Answer 11

• When fat is digested, it releases fatty acids and glycerol
• Glycerol is converted into glycerol-3-phosphate, then into Dihydroxy Acetone Phosphate (DHAP)
• DHAP is then converted Glyceraldehyde-3-Phosphate (G3P) via reaction 5 of Glycolysis and enters the GAPDH (reaction 6) reaction of Glycolysis directly

Question 12

How are fatty acids activated prior to oxidation?

Answer 12

All enzymes related to FA oxidation are within the mitochondria, so the first step is for the fatty acids obtained from the blood to get into the mitochondria, which they cannot do by themselves.

1. Fatty acids are converted into Fatty Acyl CoA on the outer mitochondrial membrane via Fatty Acyl CoA Synthase (aka Thiokinase)

Question 13

How are the fatty acids able to enter the mitochondria to undergo oxidation?

Answer 13

Fatty Acids enter the membrane via the fatty acyl-carnitine transporter. However, Fatty Acyl CoA ester formed on the outer mitochondria membrane cannot enter the mitochondria directly. So,

1. The FA is transferred to the OH group of Carnitine via Carnitine Acyl Transferase 1 (CAT-I). This fatty-acyl carnitine ester is then transported into the mitochondria
2. Now within the mitochondria, the Fa is transferred to mitochondrial CoA by CAT-II and Fatty-Acyl CoA is formed and now ready to undergo oxidation

Question 14

How does Fatty-Acyl CoA undergo oxidation within the mitochondria to produce ATP?

Answer 14

1. Beta-Oxidation of the fatty acid chain occurs which yields Acetyl-CoA
2. Acetyl-CoA enters the CAC which yields NADH, FADH2, and GTP
3. NADH and FADH2 are utilized in oxidative phosphorylation which generates ATP

Question 15

How is Beta-Oxidation of Fatty-Acyl CoA done?

Answer 15

1. Acetyl CoA Dehydrogenase catalyses the formation of a trans alpha,beta double bond using FAD as a cofactor
2. The double bond is hydrated via Enoyl-CoA-Hydratase to form L-B-Hydroxyacyl-CoA
3. Then, NAD+ dependant dehydrogenation of this product is done via B-Hydroxyacyl-CoA-Dehydrogenase to form B-Ketoacyl-CoA
4. Alpha-Carbon/Beta-Carbon bond is cleaved via a thiolysis reaction with CoA. This reaction is catalyzed via Acyl-CoA-Acetyltransferase (aka Thiolase) which produces Acetyl-CoA and a new fatty-acyl CoA with two less Carbons

Question 16

How are unsaturated fatty acids oxidized?

Answer 16

The steps for oxidation of unsaturated fatty acids are the exact same as for saturated FA’s. The only difference is the presence of the enzyme Enoyl-CoA-Isomerase which converts the cis double bond into a trans one which can then undergo regular B-oxidation

Question 17

What happens when there are more than one unsaturated double bonds in an unsaturated fatty acid? How is it oxidized?

Answer 17

When this occurs, the enzyme 2,4-dienoyl-reductase is used to saturate the second double bond.

Then, the remaining unsaturated double bond is isomerized by Enoyl-CoA-Isomerase and undergoes B-oxidation as normal

Question 18

How are Odd-Chain fatty acids Catabolized? (for example, a three chain fatty-acyl CoA)

Answer 18

In this case, the three Carbon chain is converted to 4-Carbon Methyl-Malony-CoA via Propionyl-CoA Carboxilase and Mathyl-Malony-CoA-Epimerase

The Methyl-Malony-CoA is then converted to Succinyl-CoA by Methyl-Malony-CoA Mutase, which uses vitamin B12 as a cofactor

Question 19

How is Peroxisomal Oxidation of Fatty Acids done?

Answer 19

Most steps are the same as B-Oxidation only the first dehydrogenase is not linked to ETC in peroxisomes

Electrons from the first reaction are transferred directly to O2-producing Hydrogen Peroxide

Question 20

What is Omega-Oxidation?

Answer 20

It’s a rare pathway of FA oxidation in which it starts at the farthest most carbon (omega carbon)

Question 21

What are Ketone Bodies?

Answer 21

Acetyl-CoA produced in the Liver as a result of B-Oxidation can either go to the CAC OR be converted to ketone bodies and exported to other tissues for energy generation

Ketone bodies are produced when glucose is not available as a fuel source

Question 22

In which cases is Gluconeogenesis (synthesis of Glucose) done?

Answer 22

In extreme starvation or untreated diabetes.

Gluconeogenesis uses CAC intermediates like Oxaloacetate and thus the consumption of Acetyl-CoA is slowed down. This can lead to excess Acetyl-CoA in the liver

Question 23

How does high concentration of ketone bodies affect people with untreated diabetes?

Answer 23

Concentration of ketone bodies increases which decreases the pH of the blood (makes it more acidic) This is known as “Acidosis” and can cause coma or death

Question 24

What is ketosis?

Answer 24

Ketosis is a high concentration of ketone bodies in the blood and urine.

This is caused due to high concentrations of acetoacetate, which is converted to acetone. The breath and and urine of untreated diabetics smells like acetone.